Science.gov

Sample records for long-term potentiation induction

  1. Stochastic Induction of Long-Term Potentiation and Long-Term Depression.

    PubMed

    Antunes, G; Roque, A C; Simoes-de-Souza, F M

    2016-01-01

    Long-term depression (LTD) and long-term potentiation (LTP) of granule-Purkinje cell synapses are persistent synaptic alterations induced by high and low rises of the intracellular calcium ion concentration ([Ca(2+)]), respectively. The occurrence of LTD involves the activation of a positive feedback loop formed by protein kinase C, phospholipase A2, and the extracellular signal-regulated protein kinase pathway, and its expression comprises the reduction of the population of synaptic AMPA receptors. Recently, a stochastic computational model of these signalling processes demonstrated that, in single synapses, LTD is probabilistic and bistable. Here, we expanded this model to simulate LTP, which requires protein phosphatases and the increase in the population of synaptic AMPA receptors. Our results indicated that, in single synapses, while LTD is bistable, LTP is gradual. Ca(2+) induced both processes stochastically. The magnitudes of the Ca(2+) signals and the states of the signalling network regulated the likelihood of LTP and LTD and defined dynamic macroscopic Ca(2+) thresholds for the synaptic modifications in populations of synapses according to an inverse Bienenstock, Cooper and Munro (BCM) rule or a sigmoidal function. In conclusion, our model presents a unifying mechanism that explains the macroscopic properties of LTP and LTD from their dynamics in single synapses. PMID:27485552

  2. Stochastic Induction of Long-Term Potentiation and Long-Term Depression

    PubMed Central

    Antunes, G.; Roque, A. C.; Simoes-de-Souza, F. M.

    2016-01-01

    Long-term depression (LTD) and long-term potentiation (LTP) of granule-Purkinje cell synapses are persistent synaptic alterations induced by high and low rises of the intracellular calcium ion concentration ([Ca2+]), respectively. The occurrence of LTD involves the activation of a positive feedback loop formed by protein kinase C, phospholipase A2, and the extracellular signal-regulated protein kinase pathway, and its expression comprises the reduction of the population of synaptic AMPA receptors. Recently, a stochastic computational model of these signalling processes demonstrated that, in single synapses, LTD is probabilistic and bistable. Here, we expanded this model to simulate LTP, which requires protein phosphatases and the increase in the population of synaptic AMPA receptors. Our results indicated that, in single synapses, while LTD is bistable, LTP is gradual. Ca2+ induced both processes stochastically. The magnitudes of the Ca2+ signals and the states of the signalling network regulated the likelihood of LTP and LTD and defined dynamic macroscopic Ca2+ thresholds for the synaptic modifications in populations of synapses according to an inverse Bienenstock, Cooper and Munro (BCM) rule or a sigmoidal function. In conclusion, our model presents a unifying mechanism that explains the macroscopic properties of LTP and LTD from their dynamics in single synapses. PMID:27485552

  3. Metabotropic glutamate receptors are required for the induction of long-term potentiation

    NASA Technical Reports Server (NTRS)

    Zheng, F.; Gallagher, J. P.

    1992-01-01

    Recent observations have led to the suggestion that the metabotropic glutamate receptor may play a role in the induction or maintenance of long-term potentiation (LTP). However, experimental evidence supporting a role for this receptor in the induction of LTP is still inconclusive and controversial. Here we report that, in rat dorsolateral septal nucleus (DLSN) neurons, which have the highest density of metabotropic receptors and show functional responses, the induction of LTP is not blocked by the NMDA receptor antagonist 2-amino-5-phosphonovalerate, but is blocked by two putative metabotropic glutamate receptor antagonists, L-2-amino-3-phosphonopropionic acid and L-2-amino-4-phosphonobutyrate. Furthermore, superfusion of (1S,3R)-1-aminocyclopentane-1,3-dicarboxylic acid, a selective metabotropic glutamate agonist, resulted in a long-lasting potentiation of synaptic transmission similar to that induced by tetanic stimuli. Our results demonstrated that activation of postsynaptic metabotropic receptors is both necessary and sufficient for the induction of LTP in the DLSN, and we suggest that such a mechanism may be important at other CNS synapses.

  4. PCCG-IV inhibits the induction of long-term potentiation in the dentate gyrus in vitro.

    PubMed

    Huang, L; Breakwell, N A; Rowan, M J; Anwyl, R

    1997-08-01

    The effects of two ligands with previously established high and selective potency for metabotropic glutamate receptors (mGlu receptors) group II have been investigated on the high frequency stimulation (HFS) induced long-term potentiation of the field excitatory postsynaptic potential (EPSP) in the dentate gyrus of the rat hippocampus in vitro. The ligands investigated were (2S,1'S,2'S,3'R)-2-(2"-carboxy-3'-phenylcyclopropyl)glycine (PCCG-IV) and (R,S)-alpha-methyl-4-tetrazolylphenylglycine (MTPG). PCCG-IV (10 microM) strongly inhibited the induction of long-term potentiation of the field EPSP by high frequency stimulation. MTPG (50 microM) did not inhibit the induction of long-term potentiation, but prevented the inhibition of long-term potentiation induction by PCCG-IV. The inhibition of long-term potentiation induction by PCCG-IV is suggested to be due to an agonistic action on mGlu receptor group II, probably mGlu3 receptor, as the inhibition of long-term potentiation can be reversed by the application of MTPG, a well-known selective and potent antagonist of mGlu receptor group II. PMID:9286617

  5. Learning modifies subsequent induction of long-term potentiation-like and long-term depression-like plasticity in human motor cortex.

    PubMed

    Ziemann, Ulf; Ilić, Tihomir V; Iliać, Tihomir V; Pauli, Christian; Meintzschel, Frank; Ruge, Diane

    2004-02-18

    Learning may alter rapidly the output organization of adult motor cortex. It is a long-held hypothesis that modification of synaptic strength along cortical horizontal connections through long-term potentiation (LTP) and long-term depression (LTD) forms one important mechanism for learning-induced cortical plasticity. Strong evidence in favor of this hypothesis was provided for rat primary motor cortex (M1) by showing that motor learning reduced subsequent LTP but increased LTD. Whether a similar relationship exists in humans is unknown. Here, we induced LTP-like and LTD-like plasticity in the intact human M1 by an established paired associative stimulation (PAS) protocol. PAS consisted of 200 pairs of electrical stimulation of the right median nerve, followed by focal transcranial magnetic stimulation of the hand area of the left M1 at an interval equaling the individual N20 latency of the median nerve somatosensory-evoked cortical potential (PAS(N20)) or N20-5 msec (PAS(N20-5)). PAS(N20) induced reproducibly a LTP-like long-lasting (>30 min) increase in motor-evoked potentials from the left M1 to a thumb abductor muscle of the right hand, whereas PAS(N20-5) induced a LTD-like decrease. Repeated fastest possible thumb abduction movements resulted in learning, defined by an increase in maximum peak acceleration of the practiced movements, and prevented subsequent PAS(N20)-induced LTP-like plasticity but enhanced subsequent PAS(N20-5)-induced LTD-like plasticity. The same number of repeated slow thumb abduction movements did not result in learning and had no effects on PAS-induced plasticity. Findings support the view that learning in human M1 occurs through LTP-like mechanisms.

  6. Prior Activation of Inositol 1,4,5-Trisphosphate Receptors Suppresses the Subsequent Induction of Long-Term Potentiation in Hippocampal CA1 Neurons

    ERIC Educational Resources Information Center

    Fujii, Satoshi; Yamazaki, Yoshihiko; Goto, Jun-Ichi; Fujiwara, Hiroki; Mikoshiba, Katsuhiko

    2016-01-01

    We investigated the role of inositol 1,4,5-trisphosphate receptors (IP3Rs) activated by preconditioning low-frequency afferent stimulation (LFS) in the subsequent induction of long-term potentiation (LTP) in CA1 neurons in hippocampal slices from mature guinea pigs. Induction of LTP in the field excitatory postsynaptic potential or the population…

  7. Proteasome Inhibition Enhances the Induction and Impairs the Maintenance of Late-Phase Long-Term Potentiation

    ERIC Educational Resources Information Center

    Dong, Chenghai; Upadhya, Sudarshan C.; Ding, Lan; Smith, Thuy K.; Hegde, Ashok N.

    2008-01-01

    Protein degradation by the ubiquitin-proteasome pathway plays important roles in synaptic plasticity, but the molecular mechanisms by which proteolysis regulates synaptic strength are not well understood. We investigated the role of the proteasome in hippocampal late-phase long-term potentiation (L-LTP), a model for enduring synaptic plasticity.…

  8. Protein Kinase M[Zeta] Is Essential for the Induction and Maintenance of Dopamine-Induced Long-Term Potentiation in Apical CA1 Dendrites

    ERIC Educational Resources Information Center

    Navakkode, Sheeja; Sajikumar, Sreedharan; Sacktor, Todd Charlton; Frey, Julietta U.

    2010-01-01

    Dopaminergic D1/D5-receptor-mediated processes are important for certain forms of memory as well as for a cellular model of memory, hippocampal long-term potentiation (LTP) in the CA1 region of the hippocampus. D1/D5-receptor function is required for the induction of the protein synthesis-dependent maintenance of CA1-LTP (L-LTP) through activation…

  9. Social Isolation During Adolescence Strengthens Retention of Fear Memories and Facilitates Induction of Late-Phase Long-Term Potentiation.

    PubMed

    Liu, Ji-Hong; You, Qiang-Long; Wei, Mei-Dan; Wang, Qian; Luo, Zheng-Yi; Lin, Song; Huang, Lang; Li, Shu-Ji; Li, Xiao-Wen; Gao, Tian-Ming

    2015-12-01

    Social isolation during the vulnerable period of adolescence produces emotional dysregulation that often manifests as abnormal behavior in adulthood. The enduring consequence of isolation might be caused by a weakened ability to forget unpleasant memories. However, it remains unclear whether isolation affects unpleasant memories. To address this, we used a model of associative learning to induce the fear memories and evaluated the influence of isolation mice during adolescence on the subsequent retention of fear memories and its underlying cellular mechanisms. Following adolescent social isolation, we found that mice decreased their social interaction time and had an increase in anxiety-related behavior. Interestingly, when we assessed memory retention, we found that isolated mice were unable to forget aversive memories when tested 4 weeks after the original event. Consistent with this, we observed that a single train of high-frequency stimulation (HFS) enabled a late-phase long-term potentiation (L-LTP) in the hippocampal CA1 region of isolated mice, whereas only an early-phase LTP was observed with the same stimulation in the control mice. Social isolation during adolescence also increased brain-derived neurotrophic factor (BDNF) expression in the hippocampus, and application of a tropomyosin-related kinase B (TrkB) receptor inhibitor ameliorated the facilitated L-LTP seen after isolation. Together, our results suggest that adolescent isolation may result in mental disorders during adulthood and that this may stem from an inability to forget the unpleasant memories via BDNF-mediated synaptic plasticity. These findings may give us a new strategy to prevent mental disorders caused by persistent unpleasant memories.

  10. Endogenously released ACh and exogenous nicotine differentially facilitate long-term potentiation induction in the hippocampal CA1 region of mice.

    PubMed

    Nakauchi, Sakura; Sumikawa, Katumi

    2012-05-01

    We examined the role of α7- and β2-containing nicotinic acetylcholine receptors (nAChRs) in the induction of long-term potentiation (LTP). Theta-burst stimulation (TBS), mimicking the brain's naturally occurring theta rhythm, induced robust LTP in hippocampal slices from α7 and β2 knockout mice. This suggests TBS is capable of inducing LTP without activation of α7- or β2-containing nAChRs. However, when weak TBS was applied, the modulatory effects of nicotinic receptors on LTP induction became visible. We showed that during weak TBS, activation of α7 nAChRs occurs by the release of ACh, contributing to LTP induction. Additionally, bath-application of nicotine activated β2-containing nAChRs to promote LTP induction. Despite predicted nicotine-induced desensitization, synaptically mediated activation of α7 nAChRs still occurs in the presence of nicotine and contributed to LTP induction. Optical recording of single-stimulation-evoked excitatory activity with a voltage-sensitive dye revealed enhanced excitatory activity in the presence of nicotine. This effect of nicotine was robust during high-frequency stimulation, and was accompanied by enhanced burst excitatory postsynaptic potentials. Nicotine-induced enhancement of excitatory activity was observed in slices from α7 knockout mice, but was absent in β2 knockout mice. These results suggest that the nicotine-induced enhancement of excitatory activity is mediated by β2-containing nAChRs, and is related to the nicotine-induced facilitation of LTP induction. Thus, our study demonstrates that the activation of α7- and β2-containing nAChRs differentially facilitates LTP induction via endogenously released ACh and exogenous nicotine, respectively, in the hippocampal CA1 region of mice.

  11. Possible regulatory role of dendritic spikes in induction of long-term potentiation at hippocampal schaffer collateral-CA1 synapses.

    PubMed

    Isomura, Y; Kato, N

    2000-11-10

    The amplitude of backpropagating action potentials (BAPs) is attenuated, either activity- or neurotransmitter-dependently in the apical dendrite of hippocampal pyramidal neurons. To test the possibility that this BAP attenuation may contribute to regulating the inducibility of long-term potentiation (LTP), BAPs evoked by theta-burst stimulation (TBS), a standard protocol for LTP induction, to apical dendrite synapses were subjected to perturbation by conditioning stimuli to basal dendrite synapses. During this conditioned TBS (cTBS), the amplitude of BAPs was noticeably attenuated, but that of somatic action potentials was not. In the distal dendrite area, cTBS-induced LTP was much smaller than that induced by TBS. By contrast, no difference was observed between TBS- and cTBS-induced LTP in the proximal dendrite area. These findings suggest that the activity-dependent attenuation of BAPs, propagating along the apical dendrite, may serve to regulate hippocampal synaptic plasticity.

  12. Calcium-Permeable AMPA Receptors Mediate the Induction of the Protein Kinase A-Dependent Component of Long-Term Potentiation in the Hippocampus

    PubMed Central

    Park, Pojeong; Sanderson, Thomas M.; Amici, Mascia; Choi, Sun-Lim; Bortolotto, Zuner A.; Zhuo, Min

    2016-01-01

    Two forms of NMDA receptor (NMDAR)-dependent long-term potentiation (LTP) at hippocampal CA1 synapses can be distinguished based on their sensitivity to inhibitors of protein kinase A (PKA). The PKA-dependent form requires multiple episodes of high-frequency stimulation (HFS) or theta burst stimuli (TBS) with a spacing between episodes in the order of minutes. To investigate the mechanism by which spaced episodes induce the PKA-dependent form of LTP, we have compared, in interleaved experiments, spaced (s) and compressed (c) TBS protocols in the rat CA1 synapses. We find that LTP induced by sTBS, but not that induced by cTBS, involves the insertion of calcium-permeable (CP) AMPARs, as assessed using pharmacological and electrophysiological criteria. Furthermore, a single TBS when paired with rolipram [4-(3-(cyclopentyloxy)-4-methoxyphenyl)pyrrolidin-2-one], to activate PKA, generates an LTP that also involves the insertion of CP-AMPARs. These data demonstrate that the involvement of CP-AMPARs in LTP is critically determined by the timing of the induction trigger and is associated specifically with the PKA-dependent form of LTP. SIGNIFICANCE STATEMENT Long-term potentiation is a family of synaptic mechanisms that are believed to be important for learning and memory. Two of the most extensively studied forms are triggered by the synaptic activation of NMDA receptors and expressed by changes in AMPA receptor function. They can be distinguished on the basis of their requirement for activation of a protein kinase, PKA. We show that the PKA-dependent form also involves the transient insertion of calcium-permeable AMPA receptors. These results have implications for relating synaptic plasticity to learning and memory and suggest a specific linkage between PKA activation and the rapid synaptic insertion of calcium-permeable AMPA receptors during long-term potentiation. PMID:26758849

  13. Serotonin is a facilitatory neuromodulator of synaptic transmission and "reinforces" long-term potentiation induction in the vertical lobe of Octopus vulgaris.

    PubMed

    Shomrat, T; Feinstein, N; Klein, M; Hochner, B

    2010-08-11

    The modern cephalopod mollusks (coleoids) are considered the most behaviorally advanced invertebrate, yet little is known about the neurophysiological basis of their behaviors. Previous work suggested that the vertical lobe (VL) of cephalopods is a crucial site for the learning and memory components of these behaviors. We are therefore studying the neurophysiology of the VL in Octopus vulgaris and have discovered a robust activity-dependent long-term potentiation (LTP) of the synaptic input to the VL. Moreover, we have shown that the VL and its LTP are involved in behavioral long-term memory acquisition. To advance our understanding of the VL as a learning neural network we explore the possible involvement of neuromodulation in VL function. Here we examine whether the well studied serotonergic modulation in simple models of learning in gastropods mollusks is conserved in the octopus VL. We demonstrate histochemically that the VL is innervated by afferent terminals containing 5-HT immunoreactivity (5-HT-IR). Physiologically, 5-HT has a robust facilitatory effect on synaptic transmission and activity-dependent LTP induction. These results suggest that serotonergic neuromodulation is a part of a reinforcing/reward signaling system conserved in both simple and complex learning systems of mollusks. However, there are notable functional differences. First, the effective concentration of 5-HT in the VL is rather high (100 microM); secondly, only neuropilar regions but not cell bodies in the VL are innervated by terminals containing 5-HT-IR. Thirdly, repetitive or long exposures to 5-HT do not lead to a clear long-term facilitation. We propose that in the octopus VL, while the basic facilitatory properties of molluscan 5-HT system are conserved, the system has adapted to convey signals from other brain areas to reinforce the activity-dependent associations at specific sites in the large connections matrix in the VL.

  14. Induction of long-term potentiation and depression is reflected by corresponding changes in secretion of endogenous brain-derived neurotrophic factor

    PubMed Central

    Aicardi, Giorgio; Argilli, Emanuela; Cappello, Silvia; Santi, Spartaco; Riccio, Massimo; Thoenen, Hans; Canossa, Marco

    2004-01-01

    Neurotrophins play an important role in modulating activity-dependent neuronal plasticity. In particular, threshold levels of brain-derived neurotrophic factor (BDNF) are required to induce long-term potentiation (LTP) in acute hippocampal slices. Conversely, the administration of exogenous BDNF prevents the induction of long-term depression (LTD) in the visual cortex. A long-standing missing link in the analysis of this modulatory role of BDNF was the determination of the time-course of endogenous BDNF secretion in the same organotypic preparation in which LTP and LTD are elicited. Here, we fulfilled this requirement in slices of perirhinal cortex. Classical theta-burst stimulation patterns evoking LTP lasting >180 min elicited a large increase in BDNF secretion that persisted 5-12 min beyond the stimulation period. Weaker theta-burst stimulation patterns leading only to the initial phase of LTP (≈35 min) were accompanied by a smaller increase in BDNF secretion lasting <1 min. Sequestration of BDNF by TrkB-IgG receptor bodies prevented LTP. Low-frequency stimulations leading to LTD were accompanied by reductions in BDNF secretion that never lasted beyond the duration of the stimulation. PMID:15505222

  15. Induction of long-term potentiation at perforant path dentate synapses does not affect place learning or memory.

    PubMed

    Sutherland, R J; Dringenberg, H C; Hoesing, J M

    1993-04-01

    In two experiments the authors failed to detect an effect of inducing bilateral, long-lasting synaptic potentiation at perforant path dentate synapses on spatial learning by rats in the Morris place navigation task. Daily sessions of high-frequency stimulation of perforant path axons produced large increases to an asymptotic level in population spike and field excitatory postsynaptic potential recorded in ipsilateral dentate gyrus. Place learning proceeded normally 24 hours after the last of 14 high-frequency stimulation sessions in rats that had previously mastered the procedural aspects of place navigation (Experiment 1) and in rats that were naive (Experiment 2).

  16. Long-term potentiation and long-term depression: a clinical perspective

    PubMed Central

    Bliss, Timothy V.P.; Cooke, Sam F

    2011-01-01

    Long-term potentiation and long-term depression are enduring changes in synaptic strength, induced by specific patterns of synaptic activity, that have received much attention as cellular models of information storage in the central nervous system. Work in a number of brain regions, from the spinal cord to the cerebral cortex, and in many animal species, ranging from invertebrates to humans, has demonstrated a reliable capacity for chemical synapses to undergo lasting changes in efficacy in response to a variety of induction protocols. In addition to their physiological relevance, long-term potentiation and depression may have important clinical applications. A growing insight into the molecular mechanisms underlying these processes, and technological advances in non-invasive manipulation of brain activity, now puts us at the threshold of harnessing long-term potentiation and depression and other forms of synaptic, cellular and circuit plasticity to manipulate synaptic strength in the human nervous system. Drugs may be used to erase or treat pathological synaptic states and non-invasive stimulation devices may be used to artificially induce synaptic plasticity to ameliorate conditions arising from disrupted synaptic drive. These approaches hold promise for the treatment of a variety of neurological conditions, including neuropathic pain, epilepsy, depression, amblyopia, tinnitus and stroke. PMID:21779718

  17. An interchangeable role for kainate and metabotropic glutamate receptors in the induction of rat hippocampal mossy fiber long-term potentiation in vivo

    PubMed Central

    Wallis, James L; Irvine, Mark W; Jane, David E; Lodge, David; Collingridge, Graham L; Bortolotto, Zuner A

    2015-01-01

    The roles of both kainate receptors (KARs) and metabotropic glutamate receptors (mGluRs) in mossy fiber long-term potentiation (MF-LTP) have been extensively studied in hippocampal brain slices, but the findings are controversial. In this study, we have addressed the roles of both mGluRs and KARs in MF-LTP in anesthetized rats. We found that MF-LTP could be induced in the presence of either GluK1-selective KAR antagonists or group I mGluR antagonists. However, LTP was inhibited when the group I mGluRs and the GluK1-KARs were simultaneously inhibited. Either mGlu1 or mGlu5 receptor activation is sufficient to induce this form of LTP as selective inhibition of either subtype alone, together with the inhibition of KARs, did not inhibit MF-LTP. These data suggest that mGlu1 receptors, mGlu5 receptors, and GluK1-KARs are all engaged during high-frequency stimulation, and that the activation of any one of these receptors alone is sufficient for the induction of MF-LTP in vivo. © 2015 The Authors Hippocampus Published by Wiley Periodicals, Inc. PMID:25821051

  18. Induction of hippocampal long-term potentiation during waking leads to increased extrahippocampal zif-268 expression during ensuing rapid-eye-movement sleep.

    PubMed

    Ribeiro, Sidarta; Mello, Claudio V; Velho, Tarciso; Gardner, Timothy J; Jarvis, Erich D; Pavlides, Constantine

    2002-12-15

    Rapid-eye-movement (REM) sleep plays a key role in the consolidation of memories acquired during waking (WK). The search for mechanisms underlying that role has revealed significant correlations in the patterns of neuronal firing, regional blood flow, and expression of the activity-dependent gene zif-268 between WK and subsequent REM sleep. Zif-268 integrates a major calcium signal transduction pathway and is implicated by several lines of evidence in activity-dependent synaptic plasticity. Here we report that the induction of hippocampal long-term potentiation (LTP) during WK in rats leads to an upregulation of zif-268 gene expression in extrahippocampal regions during subsequent REM sleep episodes. This upregulation occurs predominantly in the amygdala, entorhinal, and auditory cerebral cortices during the first REM sleep episodes after LTP induction and reaches somatosensory and motor cerebral cortices as REM sleep recurs. We also show that hippocampal inactivation during REM sleep blocks extrahippocampal zif-268 upregulation, indicating that cortical and amygdalar zif-268 expression during REM sleep is under hippocampal control. Thus, expression of an activity-dependent gene involved in synaptic plasticity propagates gradually from the hippocampus to extrahippocampal regions as REM sleep recurs. These findings suggest that a progressive disengagement of the hippocampus and engagement of the cerebral cortex and amygdala occurs during REM sleep. They are also consistent with the view that REM sleep constitutes a privileged window for hippocampus-driven cortical activation, which may play an instructive role in the communication of memory traces from the hippocampus to the cerebral cortex. PMID:12486186

  19. Long-term potentiation: peeling the onion.

    PubMed

    Nicoll, Roger A; Roche, Katherine W

    2013-11-01

    Since the discovery of long-term potentiation (LTP), thousands of papers have been published on this phenomenon. With this massive amount of information, it is often difficult, especially for someone not directly involved in the field, not to be overwhelmed. The goal of this review is to peel away as many layers as possible, and probe the core properties of LTP. We would argue that the many dozens of proteins that have been implicated in the phenomenon are not essential, but rather modulate, often in indirect ways, the threshold and/or magnitude of LTP. What is required is NMDA receptor activation followed by CaMKII activation. The consequence of CaMKII activation is the rapid recruitment of AMPA receptors to the synapse. This recruitment is independent of AMPA receptor subunit type, but absolutely requires an adequate pool of surface receptors. An important unresolved issue is how exactly CaMKII activation leads to modifications in the PSD to allow rapid enrichment. This article is part of the Special Issue entitled 'Glutamate Receptor-Dependent Synaptic Plasticity'. PMID:23439383

  20. Phase dependency of long-term potentiation induction during the intermittent bursts of carbachol-induced β oscillation in rat hippocampal slices.

    PubMed

    Nishimura, Motoshi; Nakatsuka, Hiroki; Natsume, Kiyohisa

    2012-01-01

    The rodent hippocampus possesses theta (θ) and beta (β) rhythms, which occur intermittently as bursts. Both rhythms are related to spatial memory processing in a novel environment. θ rhythm is related to spatial memory encoding process. β rhythm is related to the match/mismatch process. In the match/mismatch process, rodent hippocampus detects a representation matching sensory inputs of the current place among the retrieved internal representations of places. Long-term synaptic potentiation (LTP) is induced in both processes. The cholinergic agent carbachol induces intermittent θ and β oscillations in in vitro slices similar to in vivo bursts. LTP is facilitated during the generation of θ oscillation, suggesting that the facilitation of LTP is dependent upon the phases of intermittent burst (burst phases) of the oscillation. However, whether this is the case for β oscillation has not yet been studied. In the present study, LTP-inducing θ-burst stimulation was administered at the different burst phases of carbachol-induced β oscillations (CIBO), and the synaptic changes were measured at CA3-CA3 pyramidal cell synapses (CA3 synapse) and at CA3-CA1 pyramidal cell synapses (CA1 synapse). At the CA3 synapse, the largest magnitude of LTP was induced at the late burst phases of CIBO. At the CA1 synapse, LTP was induced only at the late burst phases. Modulation of LTP was suppressed when CIBO was blocked by the application of atropine at both synapses. The results suggest that the bursts of hippocampal β rhythm can determine the optimal temporal period for completing with the match/mismatch process.

  1. Activation of Metabotropic Glutamate Receptor 7 Is Required for Induction of Long-Term Potentiation at SC-CA1 Synapses in the Hippocampus

    PubMed Central

    Klar, Rebecca; Walker, Adam G.; Ghose, Dipanwita; Grueter, Brad A.; Engers, Darren W.; Hopkins, Corey R.; Lindsley, Craig W.; Xiang, Zixiu

    2015-01-01

    Of the eight metabotropic glutamate (mGlu) receptor subtypes, only mGlu7 is expressed presynaptically at the Schaffer collateral (SC)-CA1 synapse in the hippocampus in adult animals. Coupled with the inhibitory effects of Group III mGlu receptor agonists on transmission at this synapse, mGlu7 is thought to be the predominant autoreceptor responsible for regulating glutamate release at SC terminals. However, the lack of mGlu7-selective pharmacological tools has hampered direct testing of this hypothesis. We used a novel, selective mGlu7-negative allosteric modulator (NAM), ADX71743, and a newly described Group III mGlu receptor agonist, LSP4-2022, to elucidate the role of mGlu7 in modulating transmission in hippocampal area CA1 in adult C57BL/6J male mice. Interestingly, although mGlu7 agonists inhibit SC-CA1 EPSPs, we found no evidence for activation of mGlu7 by stimulation of SC-CA1 afferents. However, LSP4-2022 also reduced evoked monosynaptic IPSCs in CA1 pyramidal cells and, in contrast to its effect on SC-CA1 EPSPs, ADX71743 reversed the ability of high-frequency stimulation of SC afferents to reduce IPSC amplitudes. Furthermore, blockade of mGlu7 prevented induction of LTP at the SC-CA1 synapse and activation of mGlu7 potentiated submaximal LTP. Together, these data suggest that mGlu7 serves as a heteroreceptor at inhibitory synapses in area CA1 and that the predominant effect of activation of mGlu7 by stimulation of glutamatergic afferents is disinhibition, rather than reduced excitatory transmission. Furthermore, this mGlu7-mediated disinhibition is required for induction of LTP at the SC-CA1 synapse, suggesting that mGlu7 could serve as a novel therapeutic target for treatment of cognitive disorders. PMID:25972184

  2. Induction of hippocampal long-term potentiation increases the morphological dynamics of microglial processes and prolongs their contacts with dendritic spines

    PubMed Central

    Pfeiffer, Thomas; Avignone, Elena; Nägerl, U. Valentin

    2016-01-01

    Recently microglia, the resident immune cells of the brain, have been recognized as multi-tasking talents that are not only essential in the diseased brain, but also actively contribute to synaptic circuit remodeling during normal brain development. It is well established that microglia dynamically scan their environment and thereby establish transient physical contacts with neuronal synapses, which may allow them to sense and influence synaptic function. However, it is unknown whether and how the morphological dynamics of microglia and their physical interactions with synapses are affected by the induction of synaptic plasticity in the adult brain. To this end, we characterized the morphological dynamics of microglia and their interactions with synapses before and after the induction of synaptic plasticity (LTP) in the hippocampus by time-lapse two-photon imaging and electrophysiological recordings in acute brain slices. We demonstrate that during hippocampal LTP microglia alter their morphological dynamics by increasing the number of their processes and by prolonging their physical contacts with dendritic spines. These effects were absent in the presence of an NMDA receptor antagonist. Taken together, this altered behavior could reflect an active microglial involvement in circuit remodeling during activity-dependent synaptic plasticity in the healthy adult brain. PMID:27604518

  3. Induction of hippocampal long-term potentiation increases the morphological dynamics of microglial processes and prolongs their contacts with dendritic spines.

    PubMed

    Pfeiffer, Thomas; Avignone, Elena; Nägerl, U Valentin

    2016-01-01

    Recently microglia, the resident immune cells of the brain, have been recognized as multi-tasking talents that are not only essential in the diseased brain, but also actively contribute to synaptic circuit remodeling during normal brain development. It is well established that microglia dynamically scan their environment and thereby establish transient physical contacts with neuronal synapses, which may allow them to sense and influence synaptic function. However, it is unknown whether and how the morphological dynamics of microglia and their physical interactions with synapses are affected by the induction of synaptic plasticity in the adult brain. To this end, we characterized the morphological dynamics of microglia and their interactions with synapses before and after the induction of synaptic plasticity (LTP) in the hippocampus by time-lapse two-photon imaging and electrophysiological recordings in acute brain slices. We demonstrate that during hippocampal LTP microglia alter their morphological dynamics by increasing the number of their processes and by prolonging their physical contacts with dendritic spines. These effects were absent in the presence of an NMDA receptor antagonist. Taken together, this altered behavior could reflect an active microglial involvement in circuit remodeling during activity-dependent synaptic plasticity in the healthy adult brain. PMID:27604518

  4. Dopamine favours the emergence of long-term depression versus long-term potentiation in slices of rat prefrontal cortex.

    PubMed

    Law-Tho, D; Desce, J M; Crepel, F

    1995-03-24

    In the present study, we have investigated possible interactions between dopamine and long-term changes in synaptic efficacy induced in layer V pyramidal cells by tetanization of afferents from layer I-II. In the absence of dopamine, we confirmed that high frequency stimulation of excitatory afferents induced long-term potentiation, long-term depression or no change. Inversely, in the presence of dopamine, we have found that the same tetanus led to long-term depression in synaptic transmission in a majority of cells, but no more long-term potentiation. These results suggest that in rat prefrontal cortex, dopamine may determine the direction of activity dependent changes in synaptic efficacy and therefore, plays a functional role in the physiology of this structure.

  5. Inhibition promotes long-term potentiation at cerebellar excitatory synapses

    PubMed Central

    Binda, F.; Dorgans, K.; Reibel, S.; Sakimura, K.; Kano, M.; Poulain, B.; Isope, P.

    2016-01-01

    The ability of the cerebellar cortex to learn from experience ensures the accuracy of movements and reflex adaptation, processes which require long-term plasticity at granule cell (GC) to Purkinje neuron (PN) excitatory synapses. PNs also receive GABAergic inhibitory inputs via GCs activation of interneurons; despite the involvement of inhibition in motor learning, its role in long-term plasticity is poorly characterized. Here we reveal a functional coupling between ionotropic GABAA receptors and low threshold CaV3 calcium channels in PNs that sustains calcium influx and promotes long-term potentiation (LTP) at GC to PN synapses. High frequency stimulation induces LTP at GC to PN synapses and CaV3-mediated calcium influx provided that inhibition is intact; LTP is mGluR1, intracellular calcium store and CaV3 dependent. LTP is impaired in CaV3.1 knockout mice but it is nevertheless recovered by strengthening inhibitory transmission onto PNs; promoting a stronger hyperpolarization via GABAA receptor activation leads to an enhanced availability of an alternative Purkinje-expressed CaV3 isoform compensating for the lack of CaV3.1 and restoring LTP. Accordingly, a stronger hyperpolarization also restores CaV3-mediated calcium influx in PNs from CaV3.1 knockout mice. We conclude that by favoring CaV3 channels availability inhibition promotes LTP at cerebellar excitatory synapses. PMID:27641070

  6. Inhibition promotes long-term potentiation at cerebellar excitatory synapses.

    PubMed

    Binda, F; Dorgans, K; Reibel, S; Sakimura, K; Kano, M; Poulain, B; Isope, P

    2016-01-01

    The ability of the cerebellar cortex to learn from experience ensures the accuracy of movements and reflex adaptation, processes which require long-term plasticity at granule cell (GC) to Purkinje neuron (PN) excitatory synapses. PNs also receive GABAergic inhibitory inputs via GCs activation of interneurons; despite the involvement of inhibition in motor learning, its role in long-term plasticity is poorly characterized. Here we reveal a functional coupling between ionotropic GABAA receptors and low threshold CaV3 calcium channels in PNs that sustains calcium influx and promotes long-term potentiation (LTP) at GC to PN synapses. High frequency stimulation induces LTP at GC to PN synapses and CaV3-mediated calcium influx provided that inhibition is intact; LTP is mGluR1, intracellular calcium store and CaV3 dependent. LTP is impaired in CaV3.1 knockout mice but it is nevertheless recovered by strengthening inhibitory transmission onto PNs; promoting a stronger hyperpolarization via GABAA receptor activation leads to an enhanced availability of an alternative Purkinje-expressed CaV3 isoform compensating for the lack of CaV3.1 and restoring LTP. Accordingly, a stronger hyperpolarization also restores CaV3-mediated calcium influx in PNs from CaV3.1 knockout mice. We conclude that by favoring CaV3 channels availability inhibition promotes LTP at cerebellar excitatory synapses. PMID:27641070

  7. Inhibition promotes long-term potentiation at cerebellar excitatory synapses.

    PubMed

    Binda, F; Dorgans, K; Reibel, S; Sakimura, K; Kano, M; Poulain, B; Isope, P

    2016-09-19

    The ability of the cerebellar cortex to learn from experience ensures the accuracy of movements and reflex adaptation, processes which require long-term plasticity at granule cell (GC) to Purkinje neuron (PN) excitatory synapses. PNs also receive GABAergic inhibitory inputs via GCs activation of interneurons; despite the involvement of inhibition in motor learning, its role in long-term plasticity is poorly characterized. Here we reveal a functional coupling between ionotropic GABAA receptors and low threshold CaV3 calcium channels in PNs that sustains calcium influx and promotes long-term potentiation (LTP) at GC to PN synapses. High frequency stimulation induces LTP at GC to PN synapses and CaV3-mediated calcium influx provided that inhibition is intact; LTP is mGluR1, intracellular calcium store and CaV3 dependent. LTP is impaired in CaV3.1 knockout mice but it is nevertheless recovered by strengthening inhibitory transmission onto PNs; promoting a stronger hyperpolarization via GABAA receptor activation leads to an enhanced availability of an alternative Purkinje-expressed CaV3 isoform compensating for the lack of CaV3.1 and restoring LTP. Accordingly, a stronger hyperpolarization also restores CaV3-mediated calcium influx in PNs from CaV3.1 knockout mice. We conclude that by favoring CaV3 channels availability inhibition promotes LTP at cerebellar excitatory synapses.

  8. Long-term potentiation and evoked spike responses in the cingulate cortex of freely mobile rats.

    PubMed

    Gorkin, A G; Reymann, K G; Aleksandrov, Yu I

    2003-10-01

    Long-term potentiation of synaptic efficiency is regarded as a major candidate for the role of the physiological mechanism of long-term memory. However, the limited development of concepts of the cellular and subcellular characteristics of the induction of long-term potentiation in animals in conditions of free behavior does not correspond to the importance of this question. The present study was undertaken to determine whether the characteristics of potentiation in the cingulate cortex in response to stimulation of fibers of the subiculo-cingulate tract are truly long-term, i.e., develop through all known phases and last at least 24 h, in freely moving animals. In addition, the study aims included identification of the effects of application of blockers of different types of glutamate receptors on the development of long-term potentiation and identification of the characteristics of spike responses of single cingulate cortex neurons to stimulation of the subiculo-cingulate tract. Long-term potentiation, lasting more than 24 h, was obtained in freely moving adult rats not treated with GABA blockers. Injection of glutamate NMDA synapse blockers led to significant decreases in evoked cingulate cortex potentials in response to test stimulation. Activatory short-latency spike responses were characterized by a low probability of spike generation, and this increased with increases in the stimulation current. These data demonstrated that it is methodologically possible to compare, in freely moving rats, the involvement of individual neurons in the mechanisms involved in learning one or another type of adaptive behavior and the dynamics of their evoked spike activity during the formation of long-term potentiation. PMID:14635990

  9. Functional MRI of long-term potentiation: imaging network plasticity

    PubMed Central

    Álvarez-Salvado, Efrén; Pallarés, Vicente; Moreno, Andrea; Canals, Santiago

    2014-01-01

    Neurons are able to express long-lasting and activity-dependent modulations of their synapses. This plastic property supports memory and conveys an extraordinary adaptive value, because it allows an individual to learn from, and respond to, changes in the environment. Molecular and physiological changes at the cellular level as well as network interactions are required in order to encode a pattern of synaptic activity into a long-term memory. While the cellular mechanisms linking synaptic plasticity to memory have been intensively studied, those regulating network interactions have received less attention. Combining high-resolution fMRI and in vivo electrophysiology in rats, we have previously reported a functional remodelling of long-range hippocampal networks induced by long-term potentiation (LTP) of synaptic plasticity in the perforant pathway. Here, we present new results demonstrating an increased bilateral coupling in the hippocampus specifically supported by the mossy cell commissural/associational pathway in response to LTP. This fMRI-measured increase in bilateral connectivity is accompanied by potentiation of the corresponding polysynaptically evoked commissural potential in the contralateral dentate gyrus and depression of the inactive convergent commissural pathway to the ipsilateral dentate. We review these and previous findings in the broader context of memory consolidation. PMID:24298154

  10. Long-Term Potentiation in the Motor Cortex

    NASA Astrophysics Data System (ADS)

    Iriki, Atsushi; Pavlides, Constantine; Keller, Asaf; Asanuma, Hiroshi

    1989-09-01

    Long-term potentiation (LTP) is a model for learning and memory processes. Tetanic stimulation of the sensory cortex produces LTP in motor cortical neurons, whereas tetanization of the ventrolateral nucleus of the thalamus, which also projects to the motor cortex, does not. However, after simultaneous high-frequency stimulation of both the sensory cortex and the ventrolateral nucleus of the thalamus, LTP of thalamic input to motor cortical neurons is induced. This associative LTP occurs only in neurons in the superficial layers of the motor cortex that receive monosynaptic input from both the sensory cortex and the ventrolateral nucleus of the thalamus. Associative LTP in the motor cortex may constitute a basis for the retention of motor skills.

  11. Hippocampal Focal Knockout of CBP Affects Specific Histone Modifications, Long-Term Potentiation, and Long-Term Memory

    PubMed Central

    Barrett, Ruth M; Malvaez, Melissa; Kramar, Eniko; Matheos, Dina P; Arrizon, Abraham; Cabrera, Sara M; Lynch, Gary; Greene, Robert W; Wood, Marcelo A

    2011-01-01

    To identify the role of the histone acetyltransferase (HAT) CREB-binding protein (CBP) in neurons of the CA1 region of the hippocampus during memory formation, we examine the effects of a focal homozygous knockout of CBP on histone modifications, gene expression, synaptic plasticity, and long-term memory. We show that CBP is critical for the in vivo acetylation of lysines on histones H2B, H3, and H4. CBP's homolog p300 was unable to compensate for the loss of CBP. Neurons lacking CBP maintained phosphorylation of the transcription factor CREB, yet failed to activate CREB:CBP-mediated gene expression. Loss of CBP in dorsal CA1 of the hippocampus resulted in selective impairments to long-term potentiation and long-term memory for contextual fear and object recognition. Together, these results suggest a necessary role for specific chromatin modifications, selectively mediated by CBP in the consolidation of memories. PMID:21508930

  12. Long-Term Potentiation: From CaMKII to AMPA Receptor Trafficking.

    PubMed

    Herring, Bruce E; Nicoll, Roger A

    2016-01-01

    For more than 20 years, we have known that Ca(2+)/calmodulin-dependent protein kinase (CaMKII) activation is both necessary and sufficient for the induction of long-term potentiation (LTP). During this time, tremendous effort has been spent in attempting to understand how CaMKII activation gives rise to this phenomenon. Despite such efforts, there is much to be learned about the molecular mechanisms involved in LTP induction downstream of CaMKII activation. In this review, we highlight recent developments that have shaped our current thinking about the molecular mechanisms underlying LTP and discuss important questions that remain in the field.

  13. Laminin degradation by plasmin regulates long-term potentiation.

    PubMed

    Nakagami, Y; Abe, K; Nishiyama, N; Matsuki, N

    2000-03-01

    Plasmin is converted from its zymogen plasminogen by tissue type or urokinase type plasminogen activator (PA) and degrades many components of the extracellular matrix (ECM). To explore the possibility that the PA-plasmin system regulates synaptic plasticity, we investigated the effect of plasmin on degradation of ECM and synaptic plasticity by using organotypic hippocampal cultures. High-frequency stimulation produced long-term potentiation (LTP) in control slices, whereas the potentiation was induced but not maintained in slices pretreated with 100 nM plasmin for 6 hr. The baseline synaptic responses were not affected by pretreatment with plasmin. The impairment of LTP maintenance was not observed in slices pretreated with 100 nM plasmin for 6 hr, washed, and then cultured for 24-48 hr in the absence of plasmin. To identify substrates of plasmin, the expression of three major components of ECM, laminin, fibronectin, and type IV collagen, was investigated by immunofluorescence imaging. The three ECM components were widely distributed in the hippocampus, and only laminin was degraded by plasmin pretreatment. The expression level of laminin returned to normal levels when the slices were cultured for 24-48 hr after washout of plasmin. Furthermore, preincubation with anti-laminin antibodies prevented both the degradation of laminin and the impairment of LTP maintenance by plasmin. These results suggest that the laminin-mediated cell-ECM interaction may be necessary for the maintenance of LTP.

  14. Long-term enhancement (LTE) of postsynaptic potentials following neural conditioning, in mammalian sympathetic ganglia.

    PubMed

    Libet, B; Mochida, S

    1988-11-15

    Orthodromic, preganglionic conditioning stimulation can consistently induce long-term enhancement (LTE) (greater than 3 h) of the muscarinically mediated slow excitatory postsynaptic potential and the slow inhibitory postsynaptic potential. This was shown for superior cervical ganglia of rabbit and rat. Effective conditioning stimuli are in a physiologically observed range (3/s for 7 min, 5/s for 4 min, 10/s for 2 min, 20/s for 1 min). LTE was producible both homosynaptically and heterosynaptically. LTE can thus be associative, with conditioning synaptic input in one line inducing long-term changes in postsynaptic responses to another (heterosynaptic) input. The dopamine antagonist butaclamol depressed LTE, particularly that following the initial postconditioning period of 30 min. Adrenergic antagonists had no effect. This pharmacological evidence, coupled with the heterosynaptic induction of LTE, supports the view that neurally induced LTE may be at least partly mediated by endogenous dopamine. Another non-cholinergic but non-adrenergic transmitter (possibly a peptide) might contribute to the LTE seen in the initial 30 min postconditioning. The present, orthodromically induced LTE is clearly different from the long-term potentiation widely studied in hippocampus, etc., in the modes of induction and synaptic mediation.

  15. Circadian Regulation of Hippocampal Long-Term Potentiation

    PubMed Central

    Chaudhury, Dipesh; Wang, Louisa M.; Colwell, Christopher S.

    2008-01-01

    The goal of this study is to investigate the possible circadian regulation of hippocampal excitability and long-term potentiation (LTP) measured by stimulating the Schaffer collaterals (SC) and recording the field excitatory postsynaptic potential (fEPSP) from the CA1 dendritic layer or the population spike (PS) from the soma in brain slices of C3H and C57 mice. These 2 strains of mice were of interest because the C3H mice secrete melatonin rhythmically while the C57 mice do not. The authors found that the magnitude of the enhancement of the PS was significantly greater in LTP recorded from night slices compared to day slices of both C3H and C57 mice. They also found significant diurnal variation in the decay of LTP measured with fEPSPs, with the decay slower during the night in both strains of mice. There was evidence for a diurnal rhythm in the input/output function of pyramidal neurons measured at the soma in C57 but not C3H mice. Furthermore, LTP in the PS, measured in slices prepared during the day but recorded during the night, had a profile remarkably similar to the night group. Finally, PS recordings were carried out in slices from C3H mice maintained in constant darkness prior to experimentation. Again, the authors found that the magnitude of the enhancement of the PS was significantly greater in LTP recorded from subjective night slices compared to subjective day slices. These results provide the 1st evidence that an endogenous circadian oscillator modulates synaptic plasticity in the hippocampus. PMID:15851529

  16. Postsynaptic density-95 mimics and occludes hippocampal long-term potentiation and enhances long-term depression.

    PubMed

    Stein, Valentin; House, David R C; Bredt, David S; Nicoll, Roger A

    2003-07-01

    Previous studies have shown that overexpression of the protein PSD-95 (postsynaptic density-95) selectively enhances AMPA receptor-mediated synaptic responses in hippocampal pyramidal cells. To determine whether this effect is related to synaptic plasticity at these synapses, we examined whether PSD-95 expression mimics long-term potentiation (LTP), and also whether it influences LTP and long-term depression (LTD) in hippocampal slice cultures. Using simultaneous recording from transfected or infected cells and control pyramidal cells, we found that PSD-95, similar to LTP, increases the amplitude and frequency of miniature EPSCs. It also converts silent synapses to functional synapses, as does LTP. In addition, LTP is completely occluded in cells expressing PSD-95, whereas LTD is greatly enhanced. These results suggest that common mechanisms are involved in controlling synaptic AMPA receptors by PSD-95 and synaptic plasticity. PMID:12843250

  17. Mechanisms of CaMKII action in long-term potentiation

    PubMed Central

    Lisman, John; Yasuda, Ryohei; Raghavachari, Sridhar

    2014-01-01

    Long-term potentiation (LTP) of synaptic strength occurs during learning and can last for long periods, making it a probable mechanism for memory storage. LTP induction results in calcium entry, which activates calcium–calmodulin-dependent protein kinase II (CaMKII). CaMKII subsequently translocates to the synapse, where it binds to the NMDA-type glutamate receptors and produces potentiation by phosphorylating principal and auxiliary subunits of AMPA-type glutamate receptors. These processes all are localized to stimulated spines and account for the synapse specificity of LTP. In the later stages of LTP, CaMKII has a structural role in enlarging and strengthening the synapse. PMID:22334212

  18. Long-Term Treatment with Low Doses of Methamphetamine Promotes Neuronal Differentiation and Strengthens Long-Term Potentiation of Glutamatergic Synapses onto Dentate Granule Neurons.

    PubMed

    Baptista, Sofia; Lourenço, Joana; Milhazes, Nuno; Borges, Fernanda; Silva, Ana Paula; Bacci, Alberto

    2016-01-01

    Methamphetamine (METH) is a psychostimulant, affecting hippocampal function with disparate cognitive effects, which depends on the dose and time of administration, ranging from improvement to impairment of memory. Importantly, in the United States, METH is approved for the treatment of attention deficit hyperactivity disorder. Modifications of long-term plasticity of synapses originating from the entorhinal cortex onto dentate granule cells (DGCs) have been proposed to underlie cognitive alterations similar to those seen in METH users. However, the effects of METH on synaptic plasticity of the dentate gyrus are unknown. Here, we investigated the impact of long-term administration of METH (2 mg/kg/d) on neurogenesis and synaptic plasticity of immature and mature DGCs of juvenile mice. We used a mouse model of neurogenesis (the G42 line of GAD67-GFP), in which GFP is expressed by differentiating young DGCs. METH treatment enhanced the differentiation of GFP(+) cells, as it increased the fraction of GFP(+) cells expressing the neuronal marker NeuN, and decreased the amount of immature DGCs coexpressing doublecortin. Interestingly, METH did not change the magnitude of long-term potentiation (LTP) in more immature neurons, but facilitated LTP induction in more differentiated GFP(+) and strengthened plasticity in mature GFP(-) DGCs. The METH-induced facilitation of LTP in GFP(+) neurons was accompanied with spine enlargement. Our results reveal a specific action of long-term use of METH in the long-term plasticity of excitatory synapses onto differentiating DGCs and might have important implications toward the understanding of the synaptic basis of METH-induced cognitive alterations. PMID:27419216

  19. Long-Term Treatment with Low Doses of Methamphetamine Promotes Neuronal Differentiation and Strengthens Long-Term Potentiation of Glutamatergic Synapses onto Dentate Granule Neurons

    PubMed Central

    Milhazes, Nuno

    2016-01-01

    Abstract Methamphetamine (METH) is a psychostimulant, affecting hippocampal function with disparate cognitive effects, which depends on the dose and time of administration, ranging from improvement to impairment of memory. Importantly, in the United States, METH is approved for the treatment of attention deficit hyperactivity disorder. Modifications of long-term plasticity of synapses originating from the entorhinal cortex onto dentate granule cells (DGCs) have been proposed to underlie cognitive alterations similar to those seen in METH users. However, the effects of METH on synaptic plasticity of the dentate gyrus are unknown. Here, we investigated the impact of long-term administration of METH (2 mg/kg/d) on neurogenesis and synaptic plasticity of immature and mature DGCs of juvenile mice. We used a mouse model of neurogenesis (the G42 line of GAD67-GFP), in which GFP is expressed by differentiating young DGCs. METH treatment enhanced the differentiation of GFP+ cells, as it increased the fraction of GFP+ cells expressing the neuronal marker NeuN, and decreased the amount of immature DGCs coexpressing doublecortin. Interestingly, METH did not change the magnitude of long-term potentiation (LTP) in more immature neurons, but facilitated LTP induction in more differentiated GFP+ and strengthened plasticity in mature GFP− DGCs. The METH-induced facilitation of LTP in GFP+ neurons was accompanied with spine enlargement. Our results reveal a specific action of long-term use of METH in the long-term plasticity of excitatory synapses onto differentiating DGCs and might have important implications toward the understanding of the synaptic basis of METH-induced cognitive alterations. PMID:27419216

  20. Capsaicin-sensitive C- and A-fibre nociceptors control long-term potentiation-like pain amplification in humans.

    PubMed

    Henrich, Florian; Magerl, Walter; Klein, Thomas; Greffrath, Wolfgang; Treede, Rolf-Detlef

    2015-09-01

    Long-term potentiation in the spinal dorsal horn requires peptidergic C-fibre activation in animals. Perceptual correlates of long-term potentiation following high-frequency electrical stimulation in humans include increased sensitivity to electrical stimuli at the high frequency stimulation site (homotopic pain-long-term potentiation) and increased sensitivity to pinprick surrounding the high frequency stimulation site (heterotopic pain-long-term potentiation, equivalent to secondary hyperalgaesia). To characterize the peripheral fibre populations involved in induction of pain-long-term potentiation, we performed two selective nerve block experiments in 30 healthy male volunteers. Functional blockade of TRPV1-positive nociceptors by high-concentration capsaicin (verified by loss of heat pain) significantly reduced pain ratings to high frequency stimulation by 47% (P < 0.001), homotopic pain-long-term potentiation by 71% (P < 0.01), heterotopic pain-long-term potentiation by 92% (P < 0.001) and the area of secondary hyperalgesia by 76% (P < 0.001). The selective blockade of A-fibre conduction by nerve compression (verified by loss of first pain to pinprick) significantly reduced pain ratings to high frequency stimulation by 37% (P < 0.01), but not homotopic pain-long-term potentiation (-5%). It had a marginal effect on heterotopic pain-long-term potentiation (-35%, P = 0.059), while the area of secondary hyperalgesia remained unchanged (-2%, P = 0.88). In conclusion, all nociceptor subclasses contribute to high frequency stimulation-induced pain (with a relative contribution of C > Aδ fibres, and an equal contribution of TRPV1-positive and TRPV1-negative fibres). TRPV1-positive C-fibres are the main inducers of both homotopic and heterotopic pain-long-term potentiation. TRPV1-positive A-fibres contribute substantially to the induction of heterotopic pain-long-term potentiation. TRPV1-negative C-fibres induce a component of homotopic self-facilitation but not

  1. A Protein Synthesis and Nitric Oxide-Dependent Presynaptic Enhancement in Persistent Forms of Long-Term Potentiation

    ERIC Educational Resources Information Center

    Johnstone, Victoria P. A.; Raymond, Clarke R.

    2011-01-01

    Long-term potentiation (LTP) is an important process underlying learning and memory in the brain. At CA3-CA1 synapses in the hippocampus, three discrete forms of LTP (LTP1, 2, and 3) can be differentiated on the basis of maintenance and induction mechanisms. However, the relative roles of pre- and post-synaptic expression mechanisms in LTP1, 2,…

  2. Long-term potentiation and the role of N-methyl-D-aspartate receptors.

    PubMed

    Volianskis, Arturas; France, Grace; Jensen, Morten S; Bortolotto, Zuner A; Jane, David E; Collingridge, Graham L

    2015-09-24

    N-methyl-D-aspartate receptors (NMDARs) are known for their role in the induction of long-term potentiation (LTP). Here we start by reviewing the early evidence for their role in LTP at CA1 synapses in the hippocampus. We then discuss more recent evidence that NMDAR dependent synaptic plasticity at these synapses can be separated into mechanistically distinct components. An initial phase of the synaptic potentiation, which is generally termed short-term potentiation (STP), decays in an activity-dependent manner and comprises two components that differ in their kinetics and NMDAR subtype dependence. The faster component involves activation of GluN2A and GluN2B subunits whereas the slower component involves activation of GluN2B and GluN2D subunits. The stable phase of potentiation, commonly referred to as LTP, requires activation of primarily triheteromeric NMDARs containing both GluN2A and GluN2B subunits. In new work, we compare STP with a rebound potentiation (RP) that is induced by NMDA application and conclude that they are different phenomena. We also report that NMDAR dependent long-term depression (NMDAR-LTD) is sensitive to a glycine site NMDAR antagonist. We conclude that NMDARs are not synonymous for either LTP or memory. Whilst important for the induction of LTP at many synapses in the CNS, not all forms of LTP require the activation of NMDARs. Furthermore, NMDARs mediate the induction of other forms of synaptic plasticity and are important for synaptic transmission. It is, therefore, not possible to equate NMDARs with LTP though they are intimately linked. This article is part of a Special Issue entitled SI: Brain and Memory.

  3. Long-term potentiation and the role of N-methyl-d-aspartate receptors

    PubMed Central

    Volianskis, Arturas; France, Grace; Jensen, Morten S.; Bortolotto, Zuner A.; Jane, David E.; Collingridge, Graham L.

    2015-01-01

    N-methyl-d-aspartate receptors (NMDARs) are known for their role in the induction of long-term potentiation (LTP). Here we start by reviewing the early evidence for their role in LTP at CA1 synapses in the hippocampus. We then discuss more recent evidence that NMDAR dependent synaptic plasticity at these synapses can be separated into mechanistically distinct components. An initial phase of the synaptic potentiation, which is generally termed short-term potentiation (STP), decays in an activity-dependent manner and comprises two components that differ in their kinetics and NMDAR subtype dependence. The faster component involves activation of GluN2A and GluN2B subunits whereas the slower component involves activation of GluN2B and GluN2D subunits. The stable phase of potentiation, commonly referred to as LTP, requires activation of primarily triheteromeric NMDARs containing both GluN2A and GluN2B subunits. In new work, we compare STP with a rebound potentiation (RP) that is induced by NMDA application and conclude that they are different phenomena. We also report that NMDAR dependent long-term depression (NMDAR-LTD) is sensitive to a glycine site NMDAR antagonist. We conclude that NMDARs are not synonymous for either LTP or memory. Whilst important for the induction of LTP at many synapses in the CNS, not all forms of LTP require the activation of NMDARs. Furthermore, NMDARs mediate the induction of other forms of synaptic plasticity and are important for synaptic transmission. It is, therefore, not possible to equate NMDARs with LTP though they are intimately linked. This article is part of a Special Issue entitled SI: Brain and Memory. PMID:25619552

  4. [Long-term potentiation and unit evoked responses in the cingulate cortex of freely moving rats].

    PubMed

    Gorkin, A G; Reymann, K G; Aleksandrov, Iu I

    2002-01-01

    Long-term potentiation (LTP) of synaptic efficacy is considered to be the most probable physiological mechanism of long-term memory. However, lack of understanding of cellular and subcellular mechanisms of LTP induction in freely behaving animals does not correspond to the importance of the problem. It was tested whether the characteristics of potentiation in the cingulate cortex after tetanization of the subiculocingulate tract (SCT) meet the criteria of true LTP (that passes all known stages in its development and lasts for more than a day in freely-behaving animals). Additionally, characteristics of spike responses to SCT stimulation and the effects of application of different glutamate receptor blockers were studied. Without application of GABA receptor blockers, the LTP lasted for more than 24 hours. Application of NMDA glutamate receptor blockers significantly inhibited field potentials evoke by testing stimulation. Short-latency spike responses to SCT stimulation were recorded with low probability that increased with stimulation intensity. The obtained data reveal the possibility to compare the involvement of cingulate neurons in acquisition of adaptive behavior and changes in their spike responses during the LTP development in freely-moving rats. PMID:12528373

  5. β-Adrenergic receptor signaling and modulation of long-term potentiation in the mammalian hippocampus

    PubMed Central

    O'Dell, Thomas J.; Connor, Steven A.; Guglietta, Ryan

    2015-01-01

    Encoding new information in the brain requires changes in synaptic strength. Neuromodulatory transmitters can facilitate synaptic plasticity by modifying the actions and expression of specific signaling cascades, transmitter receptors and their associated signaling complexes, genes, and effector proteins. One critical neuromodulator in the mammalian brain is norepinephrine (NE), which regulates multiple brain functions such as attention, perception, arousal, sleep, learning, and memory. The mammalian hippocampus receives noradrenergic innervation and hippocampal neurons express β-adrenergic receptors, which are known to play important roles in gating the induction of long-lasting forms of synaptic potentiation. These forms of long-term potentiation (LTP) are believed to importantly contribute to long-term storage of spatial and contextual memories in the brain. In this review, we highlight the contributions of noradrenergic signaling in general and β-adrenergic receptors in particular, toward modulating hippocampal LTP. We focus on the roles of NE and β-adrenergic receptors in altering the efficacies of specific signaling molecules such as NMDA and AMPA receptors, protein phosphatases, and translation initiation factors. Also, the roles of β-adrenergic receptors in regulating synaptic “tagging” and “capture” of LTP within synaptic networks of the hippocampus are reviewed. Understanding the molecular and cellular bases of noradrenergic signaling will enrich our grasp of how the brain makes new, enduring memories, and may shed light on credible strategies for improving mental health through treatment of specific disorders linked to perturbed memory processing and dysfunctional noradrenergic synaptic transmission. PMID:26286656

  6. Dopaminergic neurotransmission dysfunction induced by amyloid-β transforms cortical long-term potentiation into long-term depression and produces memory impairment.

    PubMed

    Moreno-Castilla, Perla; Rodriguez-Duran, Luis F; Guzman-Ramos, Kioko; Barcenas-Femat, Alejandro; Escobar, Martha L; Bermudez-Rattoni, Federico

    2016-05-01

    Alzheimer's disease (AD) is a neurodegenerative condition manifested by synaptic dysfunction and memory loss, but the mechanisms underlying synaptic failure are not entirely understood. Although dopamine is a key modulator of synaptic plasticity, dopaminergic neurotransmission dysfunction in AD has mostly been associated to noncognitive symptoms. Thus, we aimed to study the relationship between dopaminergic neurotransmission and synaptic plasticity in AD models. We used a transgenic model of AD (triple-transgenic mouse model of AD) and the administration of exogenous amyloid-β (Aβ) oligomers into wild type mice. We found that Aβ decreased cortical dopamine levels and converted in vivo long-term potentiation (LTP) into long-term depression (LTD) after high-frequency stimulation delivered at basolateral amygdaloid nucleus-insular cortex projection, which led to impaired recognition memory. Remarkably, increasing cortical dopamine and norepinephrine levels rescued both high-frequency stimulation -induced LTP and memory, whereas depletion of catecholaminergic levels mimicked the Aβ-induced shift from LTP to LTD. Our results suggest that Aβ-induced dopamine depletion is a core mechanism underlying the early synaptopathy and memory alterations observed in AD models and acts by modifying the threshold for the induction of cortical LTP and/or LTD. PMID:27103531

  7. Dopaminergic neurotransmission dysfunction induced by amyloid-β transforms cortical long-term potentiation into long-term depression and produces memory impairment.

    PubMed

    Moreno-Castilla, Perla; Rodriguez-Duran, Luis F; Guzman-Ramos, Kioko; Barcenas-Femat, Alejandro; Escobar, Martha L; Bermudez-Rattoni, Federico

    2016-05-01

    Alzheimer's disease (AD) is a neurodegenerative condition manifested by synaptic dysfunction and memory loss, but the mechanisms underlying synaptic failure are not entirely understood. Although dopamine is a key modulator of synaptic plasticity, dopaminergic neurotransmission dysfunction in AD has mostly been associated to noncognitive symptoms. Thus, we aimed to study the relationship between dopaminergic neurotransmission and synaptic plasticity in AD models. We used a transgenic model of AD (triple-transgenic mouse model of AD) and the administration of exogenous amyloid-β (Aβ) oligomers into wild type mice. We found that Aβ decreased cortical dopamine levels and converted in vivo long-term potentiation (LTP) into long-term depression (LTD) after high-frequency stimulation delivered at basolateral amygdaloid nucleus-insular cortex projection, which led to impaired recognition memory. Remarkably, increasing cortical dopamine and norepinephrine levels rescued both high-frequency stimulation -induced LTP and memory, whereas depletion of catecholaminergic levels mimicked the Aβ-induced shift from LTP to LTD. Our results suggest that Aβ-induced dopamine depletion is a core mechanism underlying the early synaptopathy and memory alterations observed in AD models and acts by modifying the threshold for the induction of cortical LTP and/or LTD.

  8. SGK Protein Kinase Facilitates the Expression of Long-Term Potentiation in Hippocampal Neurons

    ERIC Educational Resources Information Center

    Ma, Yun L.; Tsai, Ming C.; Hsu, Wei L.; Lee, Eminy H.Y.

    2006-01-01

    Previous studies showed that the serum- and glucocorticoid-inducible kinase ("sgk") gene plays an important role in long-term memory formation. The present study further examined the role of SGK in long-term potentiation (LTP). The dominant-negative mutant of "sgk," SGKS422A, was used to inactivate SGK. Results revealed a time-dependent increase…

  9. Hippocampal CA1 Kindling but Not Long-Term Potentiation Disrupts Spatial Memory Performance

    ERIC Educational Resources Information Center

    Leung, L. Stan; Shen, Bixia

    2006-01-01

    Long-term synaptic enhancement in the hippocampus has been suggested to cause deficits in spatial performance. Synaptic enhancement has been reported after hippocampal kindling that induced repeated electrographic seizures or afterdischarges (ADs) and after long-term potentiation (LTP) defined as synaptic enhancement without ADs. We studied…

  10. Integrin dynamics produce a delayed stage of long-term potentiation and memory consolidation.

    PubMed

    Babayan, Alex H; Kramár, Enikö A; Barrett, Ruth M; Jafari, Matiar; Häettig, Jakob; Chen, Lulu Y; Rex, Christopher S; Lauterborn, Julie C; Wood, Marcelo A; Gall, Christine M; Lynch, Gary

    2012-09-12

    Memory consolidation theory posits that newly acquired information passes through a series of stabilization steps before being firmly encoded. We report here that in rat and mouse, hippocampus cell adhesion receptors belonging to the β1-integrin family exhibit dynamic properties in adult synapses and that these contribute importantly to a previously unidentified stage of consolidation. Quantitative dual immunofluorescence microscopy showed that induction of long-term potentiation (LTP) by theta burst stimulation (TBS) activates β1 integrins, and integrin-signaling kinases, at spine synapses in adult hippocampal slices. Neutralizing antisera selective for β1 integrins blocked these effects. TBS-induced integrin activation was brief (<7 min) and followed by an ∼45 min period during which the adhesion receptors did not respond to a second application of TBS. Brefeldin A, which blocks integrin trafficking to the plasma membrane, prevented the delayed recovery of integrin responses to TBS. β1 integrin-neutralizing antisera erased LTP when applied during, but not after, the return of integrin responsivity. Similarly, infusions of anti-β1 into rostral mouse hippocampus blocked formation of long-term, object location memory when started 20 min after learning but not 40 min later. The finding that β1 integrin neutralization was effective in the same time window for slice and behavioral experiments strongly suggests that integrin recovery triggers a temporally discrete, previously undetected second stage of consolidation for both LTP and memory. PMID:22973009

  11. Dynamical properties of gene regulatory networks involved in long-term potentiation

    PubMed Central

    Nido, Gonzalo S.; Ryan, Margaret M.; Benuskova, Lubica; Williams, Joanna M.

    2015-01-01

    The long-lasting enhancement of synaptic effectiveness known as long-term potentiation (LTP) is considered to be the cellular basis of long-term memory. LTP elicits changes at the cellular and molecular level, including temporally specific alterations in gene networks. LTP can be seen as a biological process in which a transient signal sets a new homeostatic state that is “remembered” by cellular regulatory systems. Previously, we have shown that early growth response (Egr) transcription factors are of fundamental importance to gene networks recruited early after LTP induction. From a systems perspective, we hypothesized that these networks will show less stable architecture, while networks recruited later will exhibit increased stability, being more directly related to LTP consolidation. Using random Boolean network (RBN) simulations we found that the network derived at 24 h was markedly more stable than those derived at 20 min or 5 h post-LTP. This temporal effect on the vulnerability of the networks is mirrored by what is known about the vulnerability of LTP and memory itself. Differential gene co-expression analysis further highlighted the importance of the Egr family and found a rapid enrichment in connectivity at 20 min, followed by a systematic decrease, providing a potential explanation for the down-regulation of gene expression at 24 h documented in our preceding studies. We also found that the architecture exhibited by a control and the 24 h LTP co-expression networks fit well to a scale-free distribution, known to be robust against perturbations. By contrast the 20 min and 5 h networks showed more truncated distributions. These results suggest that a new homeostatic state is achieved 24 h post-LTP. Together, these data present an integrated view of the genomic response following LTP induction by which the stability of the networks regulated at different times parallel the properties observed at the synapse. PMID:26300724

  12. Compensation for PKMζ in long-term potentiation and spatial long-term memory in mutant mice.

    PubMed

    Tsokas, Panayiotis; Hsieh, Changchi; Yao, Yudong; Lesburguères, Edith; Wallace, Emma Jane Claire; Tcherepanov, Andrew; Jothianandan, Desingarao; Hartley, Benjamin Rush; Pan, Ling; Rivard, Bruno; Farese, Robert V; Sajan, Mini P; Bergold, Peter John; Hernández, Alejandro Iván; Cottrell, James E; Shouval, Harel Z; Fenton, André Antonio; Sacktor, Todd Charlton

    2016-05-17

    PKMζ is a persistently active PKC isoform proposed to maintain late-LTP and long-term memory. But late-LTP and memory are maintained without PKMζ in PKMζ-null mice. Two hypotheses can account for these findings. First, PKMζ is unimportant for LTP or memory. Second, PKMζ is essential for late-LTP and long-term memory in wild-type mice, and PKMζ-null mice recruit compensatory mechanisms. We find that whereas PKMζ persistently increases in LTP maintenance in wild-type mice, PKCι/λ, a gene-product closely related to PKMζ, persistently increases in LTP maintenance in PKMζ-null mice. Using a pharmacogenetic approach, we find PKMζ-antisense in hippocampus blocks late-LTP and spatial long-term memory in wild-type mice, but not in PKMζ-null mice without the target mRNA. Conversely, a PKCι/λ-antagonist disrupts late-LTP and spatial memory in PKMζ-null mice but not in wild-type mice. Thus, whereas PKMζ is essential for wild-type LTP and long-term memory, persistent PKCι/λ activation compensates for PKMζ loss in PKMζ-null mice.

  13. Compensation for PKMζ in long-term potentiation and spatial long-term memory in mutant mice

    PubMed Central

    Tsokas, Panayiotis; Hsieh, Changchi; Yao, Yudong; Lesburguères, Edith; Wallace, Emma Jane Claire; Tcherepanov, Andrew; Jothianandan, Desingarao; Hartley, Benjamin Rush; Pan, Ling; Rivard, Bruno; Farese, Robert V; Sajan, Mini P; Bergold, Peter John; Hernández, Alejandro Iván; Cottrell, James E; Shouval, Harel Z; Fenton, André Antonio; Sacktor, Todd Charlton

    2016-01-01

    PKMζ is a persistently active PKC isoform proposed to maintain late-LTP and long-term memory. But late-LTP and memory are maintained without PKMζ in PKMζ-null mice. Two hypotheses can account for these findings. First, PKMζ is unimportant for LTP or memory. Second, PKMζ is essential for late-LTP and long-term memory in wild-type mice, and PKMζ-null mice recruit compensatory mechanisms. We find that whereas PKMζ persistently increases in LTP maintenance in wild-type mice, PKCι/λ, a gene-product closely related to PKMζ, persistently increases in LTP maintenance in PKMζ-null mice. Using a pharmacogenetic approach, we find PKMζ-antisense in hippocampus blocks late-LTP and spatial long-term memory in wild-type mice, but not in PKMζ-null mice without the target mRNA. Conversely, a PKCι/λ-antagonist disrupts late-LTP and spatial memory in PKMζ-null mice but not in wild-type mice. Thus, whereas PKMζ is essential for wild-type LTP and long-term memory, persistent PKCι/λ activation compensates for PKMζ loss in PKMζ-null mice. DOI: http://dx.doi.org/10.7554/eLife.14846.001 PMID:27187150

  14. The importance of stochastic signaling processes in the induction of long-term synaptic plasticity.

    PubMed

    De Schutter, Erik

    2013-11-01

    A stochastic model of the signaling network responsible for the induction of long-term depression (LTD) at the parallel fiber to Purkinje cell synapse is described. The model includes a PKC-ERK-cPLA2 positive feedback loop and mechanisms of AMPA receptor trafficking. It was tuned to replicate calcium uncaging experiments that cause LTD. The ultrasensitive activation of ERK makes the signaling network activity bistable, causing either LTD or not. Therefore, in single synapses only two discrete stable states (LTD and non-LTD) can be expressed. The stochastic properties of the signaling network causes threshold dithering and probabilistic expression of LTD, which allows at the macroscopic level for many different and stable mean magnitudes of depression. When the volume of a single spine is simulated no thresholds for the calcium input signal are present. Such thresholds appear only when the volume of simulation is increased by a factor 100 or more and the model output is then bistable. Similarly, deterministic solutions of the same model show only bistable behavior. LTD induction requires activation of the PKC-ERK-cPLA2 positive feedback loop but this activity is not constant: the activities of ERK and of cPLA2 fluctuate strongly. This is much less the case for PKC which is more constantly activated and thereby promotes a stable output of the pathway. PMID:23267752

  15. Short-Term Plasticity and Long-Term Potentiation in Magnetic Tunnel Junctions: Towards Volatile Synapses

    NASA Astrophysics Data System (ADS)

    Sengupta, Abhronil; Roy, Kaushik

    2016-02-01

    Synaptic memory is considered to be the main element responsible for learning and cognition in humans. Although traditionally nonvolatile long-term plasticity changes are implemented in nanoelectronic synapses for neuromorphic applications, recent studies in neuroscience reveal that biological synapses undergo metastable volatile strengthening followed by a long-term strengthening provided that the frequency of the input stimulus is sufficiently high. Such "memory strengthening" and "memory decay" functionalities can potentially lead to adaptive neuromorphic architectures. In this paper, we demonstrate the close resemblance of the magnetization dynamics of a magnetic tunnel junction (MTJ) to short-term plasticity and long-term potentiation observed in biological synapses. We illustrate that, in addition to the magnitude and duration of the input stimulus, the frequency of the stimulus plays a critical role in determining long-term potentiation of the MTJ. Such MTJ synaptic memory arrays can be utilized to create compact, ultrafast, and low-power intelligent neural systems.

  16. Long-term potentiation in spinal nociceptive pathways as a novel target for pain therapy.

    PubMed

    Ruscheweyh, Ruth; Wilder-Smith, Oliver; Drdla, Ruth; Liu, Xian-Guo; Sandkühler, Jürgen

    2011-01-01

    Long-term potentiation (LTP) in nociceptive spinal pathways shares several features with hyperalgesia and has been proposed to be a cellular mechanism of pain amplification in acute and chronic pain states. Spinal LTP is typically induced by noxious input and has therefore been hypothesized to contribute to acute postoperative pain and to forms of chronic pain that develop from an initial painful event, peripheral inflammation or neuropathy. Under this assumption, preventing LTP induction may help to prevent the development of exaggerated postoperative pain and reversing established LTP may help to treat patients who have an LTP component to their chronic pain. Spinal LTP is also induced by abrupt opioid withdrawal, making it a possible mechanism of some forms of opioid-induced hyperalgesia. Here, we give an overview of targets for preventing LTP induction and modifying established LTP as identified in animal studies. We discuss which of the various symptoms of human experimental and clinical pain may be manifestations of spinal LTP, review the pharmacology of these possible human LTP manifestations and compare it to the pharmacology of spinal LTP in rodents.

  17. Postsynaptic Signal Transduction Models for Long-Term Potentiation and Depression

    PubMed Central

    Manninen, Tiina; Hituri, Katri; Kotaleski, Jeanette Hellgren; Blackwell, Kim T.; Linne, Marja-Leena

    2010-01-01

    More than a hundred biochemical species, activated by neurotransmitters binding to transmembrane receptors, are important in long-term potentiation (LTP) and long-term depression (LTD). To investigate which species and interactions are critical for synaptic plasticity, many computational postsynaptic signal transduction models have been developed. The models range from simple models with a single reversible reaction to detailed models with several hundred kinetic reactions. In this study, more than a hundred models are reviewed, and their features are compared and contrasted so that similarities and differences are more readily apparent. The models are classified according to the type of synaptic plasticity that is modeled (LTP or LTD) and whether they include diffusion or electrophysiological phenomena. Other characteristics that discriminate the models include the phase of synaptic plasticity modeled (induction, expression, or maintenance) and the simulation method used (deterministic or stochastic). We find that models are becoming increasingly sophisticated, by including stochastic properties, integrating with electrophysiological properties of entire neurons, or incorporating diffusion of signaling molecules. Simpler models continue to be developed because they are computationally efficient and allow theoretical analysis. The more complex models permit investigation of mechanisms underlying specific properties and experimental verification of model predictions. Nonetheless, it is difficult to fully comprehend the evolution of these models because (1) several models are not described in detail in the publications, (2) only a few models are provided in existing model databases, and (3) comparison to previous models is lacking. We conclude that the value of these models for understanding molecular mechanisms of synaptic plasticity is increasing and will be enhanced further with more complete descriptions and sharing of the published models. PMID:21188161

  18. Long-term potentiation in the hippocampal slice: evidence for stimulated secretion of newly synthesized proteins

    SciTech Connect

    Duffy, C.; Teyler, T.J.; Shashoua, V.E.

    1981-06-01

    Long-term potentiation of the hippocampal slice preparation results in an increase in the incorporation of labeled valine into the proteins destined for secretion into the extracellular medium. Double-labeling methods established that the increased secretion of the labeled proteins was limited to the potentiated region of a slice; incorporation of labeled valine was increased in the hippocampus if potentiation was through the Schaffer collaterals and in the dentate if potentiation was through the perforant path. Controls for nonspecific stimulation showed no changes. There appears to be a link between long-term potentiation and the metabolic processes that lead to protein synthesis in the hippocampal slice system.

  19. The effects of long-term sleep deprivation on the long-term potentiation in the dentate gyrus and brain oxidation status in rats.

    PubMed

    Süer, Cem; Dolu, Nazan; Artis, A Seda; Sahin, Leyla; Yilmaz, Alpaslan; Cetin, Aysun

    2011-05-01

    Some evidence suggests that sleep deprivation might impair synaptic plasticity and produce oxidative stress in the hippocampus. However it is not clear whether impairment of long-term potentiation depends on the oxidative stress evoked by sleep deprivation protocol. In this study we aimed to investigate the effects of a 21-day sleep deprivation period on long-term plasticity taking into account the stressful effect of sleep deprivation. Sleep deprivation was carried out using the multiple platforms method on adult male Wistar rats. Long-term potentiation was studied in the medial perforant pathway-dentate gyrus synapses. Elevated T test was applied, and blood corticosterone levels were measured. Lipid peroxidation products in whole brain and hippocampus were determined. No significant difference was found between the sleep deprived, pedestal and cage control groups at the end of the 21-day period when corticosterone levels were compared. The results of the elevated T test indicated that sleep deprivation did not change the anxiety-like behavior of the animals. When compared with cage or pedestal control groups, sleep deprived rats displayed elevated malondialdehyde levels, and decreased superoxide dismutase and glutathione peroxidase activities together with impaired long-term potentiation maintenance. It can be argued that 21-day SD may impair the maintenance of long-term potentiation evoked in the dentate gyrus, and the balance between oxidant and antioxidant defenses of the hippocampus. PMID:21256900

  20. Two sides to long-term potentiation: a view towards reconciliation

    PubMed Central

    Padamsey, Zahid; Emptage, Nigel

    2014-01-01

    Almost since the discovery of long-term potentiation (LTP) in the hippocampus, its locus of expression has been debated. Throughout the years, convincing evidence has accumulated to suggest that LTP can be supported either presynaptically, by an increase in transmitter release, or postsynaptically, by an increase in α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor number. However, whereas postsynaptic enhancement appears to be consistently obtained across studies following LTP induction, presynaptic enhancement is not as reliably observed. Such discrepancies, along with the failure to convincingly identify a retrograde messenger required for presynaptic change, have led to the general view that LTP is mainly supported postsynaptically, and certainly, research within the field for the past decade has been heavily focused on the postsynaptic locus. Here, we argue that LTP can be expressed at either synaptic locus, but that pre- and postsynaptic forms of LTP are dissociable phenomena mediated by distinct mechanistic processes, which are sensitive to different patterns of neuronal activity. This view of LTP helps to reconcile discrepancies across the literature and may put to rest a decades-long debate. PMID:24298155

  1. Changes in cat medullary neurone firing rates and synchrony following induction of respiratory long-term facilitation

    PubMed Central

    Morris, K F; Shannon, R; Lindsey, B G

    2001-01-01

    Long-term facilitation is a respiratory memory expressed as an increase in motor output lasting more than an hour. This change is induced by repeated hypoxia, stimulation of carotid chemoreceptors, or electrical stimulation of the carotid sinus nerve or brainstem mid-line. The present work addressed the hypothesis that persistent changes in medullary respiratory neural networks contribute to long-term facilitation. Carotid chemoreceptors were stimulated by close arterial injection of CO2-saturated saline solution. Phrenic nerve efferent activity and up to 30 single medullary neurones were recorded simultaneously in nucleus tractus solitarii (NTS) including the dorsal respiratory group (DRG), Bötzinger-ventral respiratory group (Böt-VRG), and nucleus raphe obscurus of nine adult cats, anaesthetized, injected with a neuromuscular blocking agent, vagotomized and artificially ventilated. The firing rates of 87 of 105 neurones (83 %) changed following induction of long-term facilitation. Nine of eleven DRG and Böt-VRG putative premotor inspiratory neurones had increased firing rates with long-term facilitation. Fourteen of twenty-one raphe obscurus neurones with control firing rates less than 4 Hz had significant long-term increases in activity. Cross-correlogram analysis suggested that there were changes in effective connectivity of neuron pairs with long-term facilitation. Joint peristimulus time histograms and pattern detection methods used with ‘gravity’ analysis also detected changes in short time scale correlations associated with long-term facilitation. The results suggest that changes in firing rates and synchrony of VRG and DRG premotor neurones and altered effective connectivity among other functionally antecedent elements of the medullary respiratory network contribute to the expression of long-term facilitation. PMID:11306666

  2. The presence of background dopamine signal converts long-term synaptic depression to potentiation in rat prefrontal cortex.

    PubMed

    Matsuda, Yoshiki; Marzo, Aude; Otani, Satoru

    2006-05-01

    Executive functions of the brain are believed to require tonic dopamine inputs to the prefrontal cortex (PFC). It is unclear, however, how this background dopamine activity controls synaptic plasticity in the PFC, a possible underlying mechanism of executive functions. Using PFC slices, we show that pairing of dopamine with weak tetanic stimulation, a maneuver that otherwise induces NMDA receptor-independent long-term depression (LTD), induces long-term potentiation (LTP) when "primed" with dopamine. This "priming" occurs through the combined activation of D1 and D2 receptors and requires 12-40 min to develop. Moreover, concurrent synaptic activation of NMDA receptors during priming is necessary for this novel form of LTP. We suggest that a role of background dopamine signals in the PFC is to prevent high-frequency synaptic inputs from abnormally inducing LTD and to secure the induction of LTP.

  3. Induction of Long-term Depression-like Plasticity by Pairings of Motor Imagination and Peripheral Electrical Stimulation

    PubMed Central

    Jochumsen, Mads; Signal, Nada; Nedergaard, Rasmus W.; Taylor, Denise; Haavik, Heidi; Niazi, Imran K.

    2015-01-01

    Long-term depression (LTD) and long-term potentiation (LTP)-like plasticity are models of synaptic plasticity which have been associated with memory and learning. The induction of LTD and LTP-like plasticity, using different stimulation protocols, has been proposed as a means of addressing abnormalities in cortical excitability associated with conditions such as focal hand dystonia and stroke. The aim of this study was to investigate whether the excitability of the cortical projections to the tibialis anterior (TA) muscle could be decreased when dorsiflexion of the ankle joint was imagined and paired with peripheral electrical stimulation (ES) of the nerve supplying the antagonist soleus muscle. The effect of stimulus timing was evaluated by comparing paired stimulation timed to reach the cortex before, at and after the onset of imagined movement. Fourteen healthy subjects participated in six experimental sessions held on non-consecutive days. The timing of stimulation delivery was determined offline based on the contingent negative variation (CNV) of electroencephalography brain data obtained during imagined dorsiflexion. Afferent stimulation was provided via a single pulse ES to the peripheral nerve paired, based on the CNV, with motor imagination of ankle dorsiflexion. A significant decrease (P = 0.001) in the excitability of the cortical projection of TA was observed when the afferent volley from the ES of the tibial nerve (TN) reached the cortex at the onset of motor imagination based on the CNV. When TN stimulation was delivered before (P = 0.62), or after (P = 0.23) imagined movement onset there was no significant effect. Nor was a significant effect found when ES of the TN was applied independent of imagined movement (P = 0.45). Therefore, the excitability of the cortical projection to a muscle can be inhibited when ES of the nerve supplying the antagonist muscle is precisely paired with the onset of imagined movement. PMID:26648859

  4. Long-term potentiation in the hippocampus of fragile X knockout mice

    SciTech Connect

    Godfraind, J.M.; Reyniers, E.; De Boulle, K.

    1996-08-09

    To gain more insight in the physiological function of the fragile X gene (FMR1) and the mechanisms leading to fragile X syndrome, the Fmr1 gene has been inactivated in mice by gene targeting techniques. In the Morris water maze test, the Fmr1 knockout mice learn to find the hidden platform nearly as well as the control animals, but show impaired performance after the position of the platform has been modified. As malperformance in the Morris water maze test has been associated with impaired long-term potentiation (LTP), electrophysiological studies were performed in hippocampal slices of Fmr1 knockout mice to check for the presence of LTP. Judged by field extracellular excitatory postsynaptic potential recordings in the CA1 hippocampal area, Fmr1 knockout mice express LTP to a similar extent as their wild type littermates during the first 1-2 hr after high frequency stimulation. Also, short-term potentiation (STP) was similar in both types of mice. To investigate whether Fmr1 is involved in the latter stages of LTP as an immediate early gene, we compared Fmr1 mRNA quantities on northern blots after chemical induction of seizures. A transient increase in the transcription of immediate early genes is thought to be essential for the maintenance of LTP. As no increase in Fmr1 mRNA could be detected, neither in cortex nor in total brain, during the first 2{1/2} hr after pentylenetetrazol-induced seizures, it is unlikely that Fmr1 is an immediate early gene in mice. In conclusion, we found no evidence for a function of FMR1 in STP or LTP. 37 refs., 4 figs.

  5. Stimulation of raphe (obscurus) nucleus causes long-term potentiation of phrenic nerve activity in cat.

    PubMed

    Millhorn, D E

    1986-12-01

    1. The respiratory response, measured as integrated phrenic nerve activity, during and for up to an hour following 10 min of continuous electrical stimulation of raphe obscurus was quantitated in anaesthetized, artificially ventilated cats whose carotid sinus nerves and vagus nerves had been cut. End-tidal PCO2 and body temperature were kept constant with servocontrollers. 2. Stimulation of raphe obscurus caused a significant increase in both phrenic tidal activity and respiratory frequency that persisted following cessation of the stimulus. This persistent facilitation is referred to as 'long-term potentiation' of respiration. 3. Control stimulations in the parenchyma of the medulla oblongata failed to stimulate respiration and cause the long-term potentiation. 4. Both the direct facilitatory effects of raphe obscurus stimulation on phrenic nerve activity and the long-term potentiation of respiration following the stimulus were prevented by pre-treating cats with methysergide, a serotonin receptor antagonist. 5. The results are discussed in terms of the raphe obscurus being the potential source of the long-term potentiation of respiration that occurs following stimulation of carotid body afferents (Millhorn, Eldridge & Waldrop, 1980a, b). PMID:3114470

  6. Long-term athletic development, part 2: barriers to success and potential solutions.

    PubMed

    Lloyd, Rhodri S; Oliver, Jon L; Faigenbaum, Avery D; Howard, Rick; De Ste Croix, Mark B A; Williams, Craig A; Best, Thomas M; Alvar, Brent A; Micheli, Lyle J; Thomas, D Phillip; Hatfield, Disa L; Cronin, John B; Myer, Gregory D

    2015-05-01

    The first installment of this two-part commentary reviewed existing models of long-term athletic development. However, irrespective of the model that is adopted by practitioners, existing structures within competitive youth sports in addition to the prevalence of physical inactivity in a growing number of modern-day youth may serve as potential barriers to the success of any developmental pathway. The second part of this commentary will initially highlight common issues that are likely to impede the success of long-term athletic development programs and then propose solutions that will address the negative impact of such issues. PMID:25909962

  7. Long-term athletic development, part 2: barriers to success and potential solutions.

    PubMed

    Lloyd, Rhodri S; Oliver, Jon L; Faigenbaum, Avery D; Howard, Rick; De Ste Croix, Mark B A; Williams, Craig A; Best, Thomas M; Alvar, Brent A; Micheli, Lyle J; Thomas, D Phillip; Hatfield, Disa L; Cronin, John B; Myer, Gregory D

    2015-05-01

    The first installment of this two-part commentary reviewed existing models of long-term athletic development. However, irrespective of the model that is adopted by practitioners, existing structures within competitive youth sports in addition to the prevalence of physical inactivity in a growing number of modern-day youth may serve as potential barriers to the success of any developmental pathway. The second part of this commentary will initially highlight common issues that are likely to impede the success of long-term athletic development programs and then propose solutions that will address the negative impact of such issues.

  8. Enhanced AMPA Receptor Function Promotes Cerebellar Long-Term Depression Rather than Potentiation

    ERIC Educational Resources Information Center

    van Beugen, Boeke J.; Qiao, Xin; Simmons, Dana H.; De Zeeuw, Chris I.; Hansel, Christian

    2014-01-01

    Ampakines are allosteric modulators of AMPA receptors that facilitate hippocampal long-term potentiation (LTP) and learning, and have been considered for the treatment of cognition and memory deficits. Here, we show that the ampakine CX546 raises the amplitude and slows the decay time of excitatory postsynaptic currents (EPSCs) at cerebellar…

  9. Synapse Specificity of Long-Term Potentiation Breaks Down with Aging

    ERIC Educational Resources Information Center

    Ris, Laurence; Godaux, Emile

    2007-01-01

    Memory shows age-related decline. According to the current prevailing theoretical model, encoding of memories relies on modifications in the strength of the synapses connecting the different cells within a neuronal network. The selective increases in synaptic weight are thought to be biologically implemented by long-term potentiation (LTP). Here,…

  10. Long-term Potentiation at Temporoammonic Path-CA1 Synapses in Freely Moving Rats

    PubMed Central

    Gonzalez, Jossina; Villarreal, Desiree M.; Morales, Isaiah S.; Derrick, Brian E.

    2016-01-01

    Hippocampal area CA1 receives direct entorhinal layer III input via the temporoammonic path (TAP) and recent studies implicate TAP-CA1 synapses are important for some aspects of hippocampal memory function. Nonetheless, as few studies have examined TAP-CA1 synaptic plasticity in vivo, the induction and longevity of TAP-CA1 long-term potentiation (LTP) has not been fully characterized. We analyzed CA1 responses following stimulation of the medial aspect of the angular bundle and investigated LTP at medial temporoammonic path (mTAP)-CA1 synapses in freely moving rats. We demonstrate monosynaptic mTAP-CA1 responses can be isolated in vivo as evidenced by observations of independent current sinks in the stratum lacunosum moleculare of both areas CA1 and CA3 following angular bundle stimulation. Contrasting prior indications that TAP input rarely elicits CA1 discharge, we observed mTAP-CA1 responses that appeared to contain putative population spikes in 40% of our behaving animals. Theta burst high frequency stimulation of mTAP afferents resulted in an input specific and N-methyl-D-aspartate (NMDA) receptor-dependent LTP of mTAP-CA1 responses in behaving animals. LTP of mTAP-CA1 responses decayed as a function of two exponential decay curves with time constants (τ) of 2.7 and 148 days to decay 63.2% of maximal LTP. In contrast, mTAP-CA1 population spike potentiation longevity demonstrated a τ of 9.6 days. To our knowledge, these studies provide the first description of mTAP-CA1 LTP longevity in vivo. These data indicate TAP input to area CA1 is a physiologically relevant afferent system that displays robust synaptic plasticity. PMID:26903815

  11. The flavonoid baicalein promotes NMDA receptor-dependent long-term potentiation and enhances memory

    PubMed Central

    Wang, Wei; Wang, Fang; Yang, Yuan-Jian; Hu, Zhuang-Li; Long, Li-Hong; Fu, Hui; Xie, Na; Chen, Jian-Guo

    2011-01-01

    BACKGROUND AND PURPOSE There is growing interest in the physiological functions of flavonoids, especially in their effects on cognitive function and on neurodegenerative diseases. The aim of the current investigation was to evaluate the role of the flavonoid baicalein in long-term potentiation (LTP) in the hippocampal CA1 region and cognitive behavioural performance. EXPERIMENTAL APPROACH Effects of baicalein on LTP in rat hippocampal slices were investigated by electrophysiological methods. Phosphorylation of Akt (at Ser473), the extracellular signal-regulated kinase (ERK1/2) and the transcription factor cAMP response element-binding protein (CREB) (at Ser133) were analysed by Western blot. Fear conditioning was used to determine whether baicalein could improve learning and memory in rats. KEY RESULTS Baicalein enhanced the N-methyl-d-aspartate glutamate receptor-dependent LTP in a bell-shaped concentration-dependent manner. Addition of the lipoxygenase metabolites 12(S)-HETE and 12(S)-HPETE did not reverse these effects of baicalein. Baicalein treatment enhanced phosphorylation of Akt during induction of LTP with the same bell-shaped dose–response curve. LTP potentiation induced by baicalein was blocked by inhibitors of phosphoinositide 3-kinase. CREB phosphorylation was also increased in the CA1 region of baicalein-treated slices. Baicalein-treated rats performed significantly better than controls in a hippocampus-dependent contextual fear conditioning task. Furthermore, baicalein treatment selectively increased the phosphorylation of Akt and CREB in the CA1 region of hippocampus, but not in the prefrontal cortex, after fear conditioning training. CONCLUSIONS AND IMPLICATIONS Our results demonstrate that the flavonoid baicalein can facilitate memory, and therefore it might be useful in the treatment of patients with memory disorders. PMID:21133890

  12. Effects of voluntary exercise on hippocampal long-term potentiation in morphine-dependent rats.

    PubMed

    Miladi-Gorji, H; Rashidy-Pour, A; Fathollahi, Y; Semnanian, S; Jadidi, M

    2014-01-01

    This study was designed to examine the effect of voluntary exercise on hippocampal long-term potentiation (LTP) in morphine-dependent rats. The rats were randomly distributed into the saline-sedentary (Sal/Sed), the dependent-sedentary, the saline-exercise (Sal/Exc), and the dependent-exercise (D/Exc) groups. The Sal/Exc and the D/Exc groups were allowed to freely exercise in a running wheel for 10 days. The Sal/Sed and the morphine-sedentary groups were kept sedentary for the same extent of time. Morphine (10 mg/kg) was injected bi-daily (12 h interval) during 10 days of voluntary exercise. On day 11, 2h after the morphine injection, the in vivo LTP in the dentate gyrus of the hippocampus was examined. The theta frequency primed bursts were delivered to the perforant path for induction of LTP. Population spike (PS) amplitude and the field excitatory post-synaptic potentials (fEPSP) slope were measured as indices of increase in synaptic efficacy. Chronic morphine increased the mean basal EPSP, and augmented PS-LTP. Exercise significantly increased the mean baseline EPSP and PS responses, and augmented PS-LTP in both saline and morphine-treated groups. Moreover, the increase of PS-LTP in the morphine-exercise group was greater (22.5%), but not statistically significant, than that of the Sal/Exc group. These results may imply an additive effect between exercise and morphine on mechanisms of synaptic plasticity. Such an interaction between exercise and chronic morphine may influence cognitive functions in opiate addicts.

  13. Corticosterone enhances the potency of ethanol against hippocampal long-term potentiation via local neurosteroid synthesis.

    PubMed

    Izumi, Yukitoshi; O'Dell, Kazuko A; Zorumski, Charles F

    2015-01-01

    Corticosterone is known to accumulate in brain after various stressors including alcohol intoxication. Just as severe alcohol intoxication is typically required to impair memory formation only high concentrations of ethanol (60 mM) acutely inhibit long-term potentiation (LTP), a cellular memory mechanism, in naïve hippocampal slices. This LTP inhibition involves synthesis of neurosteroids, including allopregnanolone, and appears to involve a form of cellular stress. In the CA1 region of rat hippocampal slices, we examined whether a lower concentration of ethanol (20 mM) inhibits LTP in the presence of corticosterone, a stress-related modulator, and whether corticosterone stimulates local neurosteroid synthesis. Although low micromolar corticosterone alone did not inhibit LTP induction, we found that 20 mM ethanol inhibited LTP in the presence of corticosterone. At 20 mM, ethanol alone did not stimulate neurosteroid synthesis or inhibit LTP. LTP inhibition by corticosterone plus ethanol was blocked by finasteride, an inhibitor of 5α-reductase, suggesting a role for neurosteroid synthesis. We also found that corticosterone alone enhanced neurosteroid immunostaining in CA1 pyramidal neurons and that this immunostaining was further augmented by 20 mM ethanol. The enhanced neurosteroid staining was blocked by finasteride and the N-methyl-D-aspartate antagonist, 2-amino-5-phosphonovalerate (APV). These results indicate that corticosterone promotes neurosteroid synthesis in hippocampal pyramidal neurons and can participate in ethanol-mediated synaptic dysfunction even at moderate ethanol levels. These effects may contribute to the influence of stress on alcohol-induced cognitive impairment.

  14. Corticosterone enhances the potency of ethanol against hippocampal long-term potentiation via local neurosteroid synthesis

    PubMed Central

    Izumi, Yukitoshi; O’Dell, Kazuko A.; Zorumski, Charles F.

    2015-01-01

    Corticosterone is known to accumulate in brain after various stressors including alcohol intoxication. Just as severe alcohol intoxication is typically required to impair memory formation only high concentrations of ethanol (60 mM) acutely inhibit long-term potentiation (LTP), a cellular memory mechanism, in naïve hippocampal slices. This LTP inhibition involves synthesis of neurosteroids, including allopregnanolone, and appears to involve a form of cellular stress. In the CA1 region of rat hippocampal slices, we examined whether a lower concentration of ethanol (20 mM) inhibits LTP in the presence of corticosterone, a stress-related modulator, and whether corticosterone stimulates local neurosteroid synthesis. Although low micromolar corticosterone alone did not inhibit LTP induction, we found that 20 mM ethanol inhibited LTP in the presence of corticosterone. At 20 mM, ethanol alone did not stimulate neurosteroid synthesis or inhibit LTP. LTP inhibition by corticosterone plus ethanol was blocked by finasteride, an inhibitor of 5α-reductase, suggesting a role for neurosteroid synthesis. We also found that corticosterone alone enhanced neurosteroid immunostaining in CA1 pyramidal neurons and that this immunostaining was further augmented by 20 mM ethanol. The enhanced neurosteroid staining was blocked by finasteride and the N-methyl-D-aspartate antagonist, 2-amino-5-phosphonovalerate (APV). These results indicate that corticosterone promotes neurosteroid synthesis in hippocampal pyramidal neurons and can participate in ethanol-mediated synaptic dysfunction even at moderate ethanol levels. These effects may contribute to the influence of stress on alcohol-induced cognitive impairment. PMID:26190975

  15. Dentate Gyrus Granule Cell Firing Patterns Can Induce Mossy Fiber Long-Term Potentiation In Vitro

    PubMed Central

    Mistry, Rajen; Dennis, Siobhan; Frerking, Matthew; Mellor, Jack R.

    2010-01-01

    Hippocampal granule cells transmit information about behaviourally-relevant stimuli to CA3 pyramidal cells via mossy fiber synapses. These synapses express a form of long-term potentiation (mfLTP) that is non-Hebbian and does not require NMDA receptors. mfLTP is thought to be induced and expressed presynaptically, hence, the major determinant of whether mfLTP occurs is activity in the granule cells. However, it remains unclear whether mfLTP can be induced by activity patterns that granule cells exhibit in vivo, and — if so — what context generates these patterns. To address these issues, we examined granule cell activity from in vivo recordings from rats during performance of a delayed nonmatch-to-sample (DNMS) task and found that granule cells exhibit a wide range of spike patterns. In vitro slice experiments in mice demonstrated that some, but not all, of these patterns of activity could induce mfLTP. By further defining the activity thresholds for mfLTP in hippocampal slices, we found that mfLTP can only be induced by spike patterns that fire in high frequency bursts with a low average firing frequency. Using this information, we then screened for supra-threshold bursts of activity during the DNMS task. In a subset of cells, supra-threshold bursts occurred preferentially during the sampling phase of the task. If supra-threshold bursting took place later, during the delay phase, task performance was disrupted. We conclude that mfLTP can be induced by granule cell spike patterns during a memory task, and that the timing of mfLTP induction can predict task performance. PMID:20635414

  16. Long-term potentiation modulates synaptic phosphorylation networks and reshapes the structure of the postsynaptic interactome.

    PubMed

    Li, Jing; Wilkinson, Brent; Clementel, Veronica A; Hou, Junjie; O'Dell, Thomas J; Coba, Marcelo P

    2016-01-01

    The postsynaptic site of neurons is composed of more than 1500 proteins arranged in protein-protein interaction complexes, the composition of which is modulated by protein phosphorylation through the actions of complex signaling networks. Components of these networks function as key regulators of synaptic plasticity, in particular hippocampal long-term potentiation (LTP). The postsynaptic density (PSD) is a complex multicomponent structure that includes receptors, enzymes, scaffold proteins, and structural proteins. We triggered LTP in the mouse hippocampus CA1 region and then performed large-scale analyses to identify phosphorylation-mediated events in the PSD and changes in the protein-protein interactome of the PSD that were associated with LTP induction. Our data indicated LTP-induced reorganization of the PSD. The dynamic reorganization of the PSD links glutamate receptor signaling to kinases (writers) and phosphatases (erasers), as well as the target proteins that are modulated by protein phosphorylation and the proteins that recognize the phosphorylation status of their binding partners (readers). Protein phosphorylation and protein interaction networks converged at highly connected nodes within the PSD network. Furthermore, the LTP-regulated phosphoproteins, which included the scaffold proteins Shank3, Syngap1, Dlgap1, and Dlg4, represented the "PSD risk" for schizophrenia and autism spectrum disorder, such that without these proteins in the analysis, the association with the PSD and these two psychiatric diseases was not present. These data are a rich resource for future studies of LTP and suggest that the PSD holds the keys to understanding the molecular events that contribute to complex neurological disorders that affect synaptic plasticity. PMID:27507650

  17. Learning, memory and long-term potentiation are altered in Nedd4 heterozygous mice.

    PubMed

    Camera, Daria; Coleman, Harold A; Parkington, Helena C; Jenkins, Trisha A; Pow, David V; Boase, Natasha; Kumar, Sharad; Poronnik, Philip

    2016-04-15

    The consolidation of short-term memory into long-term memory involves changing protein level and activity for the synaptic plasticity required for long-term potentiation (LTP). AMPA receptor trafficking is a key determinant of LTP and recently ubiquitination by Nedd4 has been shown to play an important role via direct action on the GluA1 subunit, although the physiological relevance of these findings are yet to be determined. We therefore investigated learning and memory in Nedd4(+/-) mice that have a 50% reduction in levels of Nedd4. These mice showed decreased long-term spatial memory as evidenced by significant increases in the time taken to learn the location of and subsequently find a platform in the Morris water maze. In contrast, there were no significant differences between Nedd4(+/+) and Nedd4(+/-) mice in terms of short-term spatial memory in a Y-maze test. Nedd4(+/-) mice also displayed a significant reduction in post-synaptic LTP measured in hippocampal brain slices. Immunofluorescence of Nedd4 in the hippocampus confirmed its expression in hippocampal neurons of the CA1 region. These findings indicate that reducing Nedd4 protein by 50% significantly impairs LTP and long-term memory thereby demonstrating an important role for Nedd4 in these processes.

  18. Long-term Potentiation of Perforant Pathway-dentate Gyrus Synapse in Freely Behaving Mice

    PubMed Central

    Blaise, J. Harry

    2013-01-01

    Studies of long-term potentiation of synaptic efficacy, an activity-dependent synaptic phenomenon having properties that make it attractive as a potential cellular mechanism underlying learning and information storage, have long been used to elucidate the physiology of various neuronal circuits in the hippocampus, amygdala, and other limbic and cortical structures. With this in mind, transgenic mouse models of neurological diseases represent useful platforms to conduct long-term potentiation (LTP) studies to develop a greater understanding of the role of genes in normal and abnormal synaptic communication in neuronal networks involved in learning, emotion and information processing. This article describes methodologies for reliably inducing LTP in the freely behaving mouse. These methodologies can be used in studies of transgenic and knockout freely behaving mouse models of neurodegenerative diseases. PMID:24327052

  19. DEVELOPMENTAL LEAD (PB) EXPOSURE REDUCES THE ABILITY OF THE NNDA ANTAGONIST MK801 TO SUPPRESS LONG-TERM POTENTIATION (LTP) IN THE RAT DENTATE GYRUS, IN VIVO

    EPA Science Inventory

    Chronic developmental lead (Pb) exposure increases the threshold and enhances decay of long-term potentiation (LTP) in the dentate gyrus of the hippocampal formation. MK-801 and other antagonists of the N-methyl-D-aspartate (NMDA) glutamate receptor subtype impair induction of LT...

  20. Improving potato drought tolerance through the induction of long-term water stress memory.

    PubMed

    Ramírez, D A; Rolando, J L; Yactayo, W; Monneveux, P; Mares, V; Quiroz, R

    2015-09-01

    Knowledge of drought tolerance in potato is limited and very little is known about stress memory in this crop. In the present study, long-term stress memory was tested on tuber yield and drought tolerance related traits in three potato varieties (Unica, Désirée and Sarnav) with contrasted yields under water restriction. Seed tubers produced by plants grown under non-restricted (non-primed tubers) and restricted (primed tubers) water conditions were sown and exposed to similar watering treatments. Tuber yield and leaf greenness of plants from primed and non-primed seeds as well as tuber carbon isotope discrimination (Δ(13)C) and antioxidant activity (AA) responses to watering treatments were compared. Higher tuber yield, both under non-restricted and restricted water regimes, was produced by primed Sarnav plants. The decrease of tuber yield and Δ(13)C with water restriction was lower in primed Unica plants. Long-term stress memory consequently appears to be highly genotype-dependent in potato. Its expression in plants originated from primed tubers and facing water restriction seems to be positively associated to the degree of inherent capability of the cultivar to yield under water restriction. However, other effects of priming appear to be genotype-independent as priming enhanced the tuber AA in response to water restriction in the three varieties.

  1. Mechanisms of induction and expression of long-term depression at GABAergic synapses in the neonatal rat hippocampus.

    PubMed

    Caillard, O; Ben-Ari, Y; Gaïarsa, J L

    1999-09-01

    Synaptic plasticity at excitatory glutamatergic synapses is believed to be instrumental in the maturation of neuronal networks. Using whole-cell patch-clamp recordings, we have studied the mechanisms of induction and expression of long-term depression at excitatory GABAergic synapses in the neonatal rat hippocampus (LTD(GABA-A)). We report that the induction of LTD(GABA-A) requires a GABA(A) receptor-mediated membrane depolarization, which is necessary to remove the Mg(2+) block from postsynaptic NMDA receptors. LTD(GABA-A) is associated with an increase in the coefficient of variation of evoked GABA(A) receptor-mediated synaptic currents and a decrease in the frequency, but not amplitude, of Sr(2+)-induced asynchronous GABA(A) quantal events. We conclude that LTD(GABA-A) induction requires the activation of both GABA(A) and NMDA postsynaptic receptors and that its expression is likely presynaptic.

  2. The evidence for hippocampal long-term potentiation as a basis of memory for simple tasks.

    PubMed

    Izquierdo, Iván; Cammarota, Martín; Da Silva, Weber C; Bevilaqua, Lia R M; Rossato, Janine I; Bonini, Juliana S; Mello, Pamela; Benetti, Fernando; Costa, Jaderson C; Medina, Jorge H

    2008-03-01

    Long-term potentiation (LTP) is the enhancement of postsynaptic responses for hours, days or weeks following the brief repetitive afferent stimulation of presynaptic afferents. It has been proposed many times over the last 30 years to be the basis of long-term memory. Several recent findings finally supported this hypothesis: a) memory formation of one-trial avoidance learning depends on a series of molecular steps in the CA1 region of the hippocampus almost identical to those of LTP in the same region; b)hippocampal LTP in this region accompanies memory formation of that task and of another similar task. However, CA1 LTP and the accompanying memory processes can be dissociated, and in addition plastic events in several other brain regions(amygdala, entorhinal cortex, parietal cortex) are also necessary for memory formation of the one-trial task, and perhaps of many others.

  3. Gracilis myocutaneous flap: evaluation of potential risk factors and long-term donor-site morbidity.

    PubMed

    Papadopoulos, Othon; Konofaos, Petros; Georgiou, Panos; Chrisostomidis, Chrisostomos; Tsantoulas, Zacharias; Karypidis, Dimitrios; Kostakis, Alkiviadis

    2011-09-01

    This study reviewed our experience with the gracilis myocutaneous (GMC) flap, potential risk factors for flap necrosis, and long-term morbidity at the donor-site. From 1993 to 2002, 29 GMC flaps were harvested from 27 patients (pedicled n = 21 and free n = 8). The overall incidence of flap necrosis was 13.79% (partial (n = 2) and total (n = 2) necrosis). Flap necrosis was correlated with body mass index >25 (P = 0.022), with smoking (P = 0.04 9) and with radiation therapy at the recipient site (P = 0.020). The long-term morbidity at the donor-site was low, except for scar appearance (17.24%), thigh contour deformity (58.62%), and hypoesthesia (17.24%). Significant age and gender differences were seen for ranking of scar ugliness, with females (P = 0.0061) and younger patients (age ≤55) (P = 0.046) assigned higher values. Significant age differences were seen for ranking of thigh contour deformity, with younger patients assigned higher values (P = 0.0012). In conclusion, patient overweight, smoking, and previous radiation therapy at the recipient site may be the "potential risk factors" for flap necrosis. The long-term morbidity at the donor-site was low, which was in agreement with previous reported studies. A larger series would be the subject of a future study.

  4. Opposing effects of PSD-93 and PSD-95 on long-term potentiation and spike timing-dependent plasticity

    PubMed Central

    Carlisle, Holly J; Fink, Ann E; Grant, Seth G N; O'Dell, Thomas J

    2008-01-01

    The membrane-associated guanylate kinases (MAGUKs) PSD-95, PSD-93 and SAP102 are thought to have crucial roles in both AMPA receptor trafficking and formation of NMDA receptor-associated signalling complexes involved in synaptic plasticity. While PSD-95, PSD-93, and SAP102 appear to have similar roles in AMPA receptor trafficking, it is not known whether these MAGUKs also have functionally similar roles in synaptic plasticity. To explore this issue we examined several properties of basal synaptic transmission in the hippocampal CA1 region of PSD-93 and PSD-95 mutant mice and compared the ability of a number of different synaptic stimulation protocols to induce long-term potentiation (LTP) and long-term depression (LTD) in these mutants. We find that while both AMPA and NMDA receptor-mediated synaptic transmission are normal in PSD-93 mutants, PSD-95 mutant mice exhibit clear deficits in AMPA receptor-mediated transmission. Moreover, in contrast to the facilitation of LTP induction and disruption of LTD observed in PSD-95 mutant mice, PSD-93 mutant mice exhibit deficits in LTP and normal LTD. Our results suggest that PSD-95 has a unique role in AMPA receptor trafficking at excitatory synapses in the hippocampus of adult mice and indicate that PSD-93 and PSD-95 have essentially opposite roles in LTP, perhaps because these MAGUKs form distinct NMDA receptor signalling complexes that differentially regulate the induction of LTP by different patterns of synaptic activity. PMID:18936077

  5. Nitric oxide-dependent long-term depression but not endocannabinoid-mediated long-term potentiation is crucial for visual recognition memory

    PubMed Central

    Tamagnini, Francesco; Barker, Gareth; Warburton, E Clea; Burattini, Costanza; Aicardi, Giorgio; Bashir, Zafar I

    2013-01-01

    Synaptic plasticity in perirhinal cortex is essential for recognition memory. Nitric oxide and endocannabinoids (eCBs), which are produced in the postsynaptic cell and act on the presynaptic terminal, are implicated in mechanisms of long-term potentiation (LTP) and long-term depression (LTD) in other brain regions. In this study, we examine these two retrograde signalling cascades in perirhinal cortex synaptic plasticity and in visual recognition memory in the rat. We show that inhibition of NO-dependent signalling prevented both carbachol- and activity (5 Hz)-dependent LTD but not activity (100 Hz theta burst)-dependent LTP in the rat perirhinal cortex in vitro. In contrast, inhibition of the eCB-dependent signalling prevented LTP but not the two forms of LTD in vitro. Local administration into perirhinal cortex of the nitric oxide synthase inhibitor NPA (2 μm) disrupted acquisition of long-term visual recognition memory. In contrast, AM251 (10 μm), a cannabinoid receptor 1 antagonist, did not impair visual recognition memory. The results of this study demonstrate dissociation between putative retrograde signalling mechanisms in LTD and LTP in perirhinal cortex. Thus, LTP relies on cannabinoid but not NO signalling, whilst LTD relies on NO- but not eCB-dependent signalling. Critically, these results also establish, for the first time, that NO- but not eCB-dependent signalling is important in perirhinal cortex-dependent visual recognition memory. PMID:23671159

  6. Local and descending circuits regulate long-term potentiation and zif268 expression in spinal neurons.

    PubMed

    Rygh, Lars Jørgen; Suzuki, Rie; Rahman, Wahida; Wong, Yuk; Vonsy, Jean Laurent; Sandhu, Hardip; Webber, Mark; Hunt, Stephen; Dickenson, Anthony H

    2006-08-01

    Long-term potentiation (LTP), a use dependent long-lasting modification of synaptic strength, was first discovered in the hippocampus and later shown to occur in sensory areas of the spinal cord. Here we demonstrate that spinal LTP requires the activation of a subset of superficial spinal dorsal horn neurons expressing the neurokinin-1 receptor (NK1-R) that have previously been shown to mediate certain forms of hyperalgesia. These neurons participate in local spinal sensory processing, but are also the origin of a spino-bulbo-spinal loop driving a 5-hydroxytryptamine 3 receptor (5HT3-R)- mediated descending facilitation of spinal pain processing. Using a saporin-substance P conjugate to produce site-specific neuronal ablation, we demonstrate that NK1-R expressing cells in the superficial dorsal horn are crucial for the generation of LTP-like changes in neuronal excitability in deep dorsal horn neurons and this is modulated by descending 5HT3-R-mediated facilitatory controls. Hippocampal LTP is associated with early expression of the immediate-early gene zif268 and knockout of the gene leads to deficits in long-term LTP and learning and memory. We found that spinal LTP is also correlated with increased neuronal expression of zif268 in the superficial dorsal horn and that zif268 antisense treatment resulted in deficits in the long-term maintenance of inflammatory hyperalgesia. Our results support the suggestion that the generation of LTP in dorsal horn neurons following peripheral injury may be one mechanism whereby acute pain can be transformed into a long-term pain state. PMID:16930406

  7. Long-term potentiation in spinal nociceptive systems--how acute pain may become chronic.

    PubMed

    Rygh, Lars Jørgen; Svendsen, Frode; Fiskå, Atle; Haugan, Frøydis; Hole, Kjell; Tjølsen, Arne

    2005-11-01

    Chronic pain is a major problem since it is difficult to treat and the understanding of the underlying neurobiology is sparse. The mechanisms underpinning the transition of acute into chronic pain remain unclear. However, long-term potentiation (LTP) in spinal nociceptive systems may be one such mechanism. Here, we briefly review the literature regarding LTP in spinal nociceptive systems including our own data on LTP in deep convergent nociceptive neurons. Furthermore, we discuss the role of this phenomenon in understanding the neurobiology of chronic pain and the possible therapeutic implications.

  8. Running enhances neurogenesis, learning, and long-term potentiation in mice

    PubMed Central

    van Praag, Henriette; Christie, Brian R.; Sejnowski, Terrence J.; Gage, Fred H.

    1999-01-01

    Running increases neurogenesis in the dentate gyrus of the hippocampus, a brain structure that is important for memory function. Consequently, spatial learning and long-term potentiation (LTP) were tested in groups of mice housed either with a running wheel (runners) or under standard conditions (controls). Mice were injected with bromodeoxyuridine to label dividing cells and trained in the Morris water maze. LTP was studied in the dentate gyrus and area CA1 in hippocampal slices from these mice. Running improved water maze performance, increased bromodeoxyuridine-positive cell numbers, and selectively enhanced dentate gyrus LTP. Our results indicate that physical activity can regulate hippocampal neurogenesis, synaptic plasticity, and learning. PMID:10557337

  9. Low-carbohydrate diets: what are the potential short- and long-term health implications?

    PubMed

    Bilsborough, Shane A; Crowe, Timothy C

    2003-01-01

    Low-carbohydrate diets for weight loss are receiving a lot of attention of late. Reasons for this interest include a plethora of low-carbohydrate diet books, the over-sensationalism of these diets in the media and by celebrities, and the promotion of these diets in fitness centres and health clubs. The re-emergence of low-carbohydrate diets into the spotlight has lead many people in the general public to question whether carbohydrates are inherently 'bad' and should be limited in the diet. Although low-carbohydrate diets were popular in the 1970s they have resurged again yet little scientific fact into the true nature of how these diets work or, more importantly, any potential for serious long-term health risks in adopting this dieting practice appear to have reached the mainstream literature. Evidence abounds that low-carbohydrate diets present no significant advantage over more traditional energy-restricted, nutritionally balanced diets both in terms of weight loss and weight maintenance. Studies examining the efficacy of using low-carbohydrate diets for long-term weight loss are few in number, however few positive benefits exist to promote the adoption of carbohydrate restriction as a realistic, and more importantly, safe means of dieting. While short-term carbohydrate restriction over a period of a week can result in a significant loss of weight (albeit mostly from water and glycogen stores), of serious concern is what potential exists for the following of this type of eating plan for longer periods of months to years. Complications such as heart arrhythmias, cardiac contractile function impairment, sudden death, osteoporosis, kidney damage, increased cancer risk, impairment of physical activity and lipid abnormalities can all be linked to long-term restriction of carbohydrates in the diet. The need to further explore and communicate the untoward side-effects of low-carbohydrate diets should be an important public health message from nutrition professionals

  10. Potential of mass trapping for long-term pest management and eradication of invasive species.

    PubMed

    El-Sayed, A M; Suckling, D M; Wearing, C H; Byers, J A

    2006-10-01

    Semiochemical-based pest management programs comprise three major approaches that are being used to provide environmentally friendly control methods of insect pests: mass trapping, "lure and kill," and mating disruption. In this article, we review the potential of mass trapping in long-term pest management as well as in the eradication of invasive species. We discuss similarities and differences between mass trapping and other two main approaches of semiochemical-based pest management programs. We highlight several study cases where mass trapping has been used either in long-term pest management [e.g., codling moth, Cydia pomonella (L.); pink bollworm, Pectinophora gossypiella (Saunders); bark beetles, palm weevils, corn rootworms (Diabrotica spp.); and fruit flies] or in eradication of invasive species [e.g., gypsy moth, Lymantria dispar (L.); and boll weevil, Anthonomus grandis grandis Boheman). We list the critical issues that affect the efficacy of mass trapping and compare these with previously published models developed to investigate mass trapping efficacy in pest control. We conclude that mass trapping has good potential to suppress or eradicate low-density, isolated pest populations; however, its full potential in pest management has not been adequately realized and therefore encourages further research and development of this technology. PMID:17066782

  11. Post-weaning mice fed exclusively milk have deficits in induction of long-term depression in the CA1 hippocampal region and spatial learning and memory.

    PubMed

    Nishie, Hideaki; Miyata, Ryouhei; Fujikawa, Ryu; Kinoshita, Ken-ichi; Muroi, Yoshikage; Ishii, Toshiaki

    2012-08-01

    Previously, we have found that post-weaning mice fed exclusively milk display low-frequency exploratory behavior compared to mice fed a food pellet diet (Ishii et al., 2005a). Because cognitive functions play a key role in animal exploration, in the present study we examined the effect of an exclusively milk formula diet on spatial learning and memory in a water maze and also on induction of long-term potentiation (LTP) and long-term depression (LTD) at the Schaffer collateral-CA1 synapse in the hippocampus. Exclusively milk-fed mice exhibited slower learning and memory deficits in hidden water maze tests as compared with pellet-fed mice. Moreover, milk-fed mice showed a significant inhibition of LTD but a normal induction of LTP. Despite these functional deficits, adult neurogenesis in the dentate gyrus of the hippocampus, which has been proposed to have a causal relationship to spatial memory, was stimulated in milk-fed mice. These result suggest that an exclusively milk formula diet after weaning leads to a stimulation of hippocampal neurogenesis but causes deficits in the induction of LTD in the CA1 hippocampal region and impairment of spatial learning and memory.

  12. Long-term changes in pigmentation of arctic Daphnia provide potential for reconstructing aquatic UV exposure

    NASA Astrophysics Data System (ADS)

    Nevalainen, Liisa; Rantala, Marttiina V.; Luoto, Tomi P.; Ojala, Antti E. K.; Rautio, Milla

    2016-07-01

    Despite the biologically damaging impacts of solar ultraviolet radiation (UV) in nature, little is known about its natural variability, forcing mechanisms, and long-term effects on ecosystems and organisms. Arctic zooplankton, for example the aquatic keystone genus Daphnia (Crustacea, Cladocera) responds to biologically damaging UV by utilizing photoprotective strategies, including pigmentation. We examined the preservation and content of UV-screening pigments in fossil Daphnia remains (ephippia) in two arctic lake sediment cores from Cornwallis Island (Lake R1), Canada, and Spitsbergen (Lake Fugledammen), Svalbard. The aims were to document changes in the degree of UV-protective pigmentation throughout the past centuries, elucidate the adaptive responses of zooplankton to long-term variations in UV exposure, and estimate the potential of fossil zooplankton pigments in reconstructing aquatic UV regimes. The spectroscopic absorbance measurements of fossil Daphnia ephippia under UV (280-400 nm) and visible light (400-700 nm) spectral ranges indicated that melanin (absorbance maxima at UV wavebands 280-350 nm) and carotenoids (absorbance maxima at 400-450 nm) pigments were preserved in the ephippia in both sediment cores. Downcore measurements of the most important UV-protective pigment melanin (absorbance measured at 305 and 340 nm) showed marked long-term variations in the degree of melanisation. These variations likely represented long-term trends in aquatic UV exposure and were positively related with solar radiation intensity. The corresponding trends in melanisation and solar activity were disrupted at the turn of the 20th century in R1, but remained as strong in Fugledammen. The reversed trends in the R1 core were simultaneous with a significant aquatic community reorganization taking place in the lake, suggesting that recent environmental changes, likely related to climate warming had a local effect on pigmentation strategies. This time horizon is also

  13. [Determination of geroprotective potential of sodium butyrate in Drosophila melanogaster: long-term effects].

    PubMed

    2013-01-01

    We have previously shown (Vaiserman A. M. et al., 2012) that the dietary supplementation with histone deacetylase inhibitor sodium butyrate (SB) throughout adult stage or both pre-adult and adult stages results in increase of life span (LS) in Drosophila melanogaster. It was suggested that because of the impact of SB on epigenetic control of gene function and therefore possibility of long-term effects, SB supplementation during the larval stage of development only may also increase adult LS. The present study was carried out to verify that assumption. The nutritional supplementation with SB during the larval stage at the concentration of 20 mmol/l resulted in a significant increase in the male mean LS; maximum LS was significantly increased in males treated with SB at concentrations of 10, 20 and 40 mmol/l. Female mean LS was unchanged following the SB administration; maximum LS was significantly increased in female group treated with SB at concentration of 10 mmol/l only. Female reproductive activity was the same in all groups. To test the hypothesis that the observed long-term effect of SB exposure on the flies' longevity could be caused by the induction of persistent epigenetic changes, the levels of expression of the longevity-associated genes (hsp70, sir2 and InR) were determined. The expression level of sir2 gene, known to mediate longevity in the fly through a pathway related to calorie restriction, in the group treated at the larval stage with 20 mmol/l SB was significantly higher after the stress (starvation) than in the control group.

  14. A post-tetanic time window for the reinforcement of long-term potentiation by appetitive and aversive stimuli

    PubMed Central

    Seidenbecher, Thomas; Reymann, Klaus G.; Balschun, Detlef

    1997-01-01

    Current theories on the encoding and storage of information in the brain commonly suppose that a short-term memory is converted into a lasting one; thus, it becomes consolidated over time. Within a finite period after training, such a short-term memory can be reinforced by behavioral and humoral stimuli. We have found that, long-term potentiation (LTP), a likely candidate for a memory-encoding mechanism at the cellular level, displays similar features. LTP in the dentate gyrus of freely moving rats was reinforced after its induction by appetitive and aversive stimuli. The efficacy of these stimuli terminates about 1 h after tetanization, which may reflect the time constants of the mechanisms underlying the consolidation that takes place. The reinforcement by appetitive and aversive stimulation was blocked by the β-adrenergic antagonist propranolol, implicating norepinephrine in the underlying cellular processes. PMID:9037081

  15. Non-Hebbian properties of long-term potentiation enable high-capacity encoding of temporal sequences.

    PubMed

    Granger, R; Whitson, J; Larson, J; Lynch, G

    1994-10-11

    A hypothesis commonly found in biological and computational studies of synaptic plasticity embodies a version of the 1949 postulate of Hebb that coactivity of pre- and postsynaptic elements results in increased efficacy of their synaptic contacts. This general proposal presaged the identification of the first and still only known long-lasting synaptic plasticity mechanism, long-term potentiation (LTP). Yet the detailed physiology of LTP induction and expression differs in many specifics from Hebb's rule. Incorporation of these physiological LTP constraints into a simple non-Hebbian network model enabled development of "sequence detectors" that respond preferentially to the sequences on which they were trained. The network was found to have unexpected capacity (e.g., 50 x 10(6) random sequences in a network of 10(5) cells), which scales linearly with network size, thereby addressing the question of memory capacity in brain circuitry of realistic size.

  16. Steel mutant mice are deficient in hippocampal learning but not long-term potentiation.

    PubMed Central

    Motro, B; Wojtowicz, J M; Bernstein, A; van der Kooy, D

    1996-01-01

    Mice carrying mutations in either the dominant white-spotting (W) or Steel (Sl) loci exhibit deficits in melanogenesis, gametogenesis, and hematopoiesis. W encodes the Kit receptor tyrosine kinase, while Sl encodes the Kit ligand, Steel factor, and the receptor-ligand pair are contiguously expressed at anatomical sites expected from the phenotypes of W and Sl mice. The c-kit and Steel genes are also both highly expressed in the adult murine hippocampus: Steel is expressed in dentate gyrus neurons whose mossy fiber axons synapse with the c-kit expressing CA3 pyramidal neurons. We report here that Sl/Sld mutant mice have a specific deficit in spatial learning. These mutant mice are also deficient in baseline synaptic transmission between the dentate gyrus and CA3 but show normal long-term potentiation in this pathway. These observations demonstrate a role for Steel factor/Kit signaling in the adult nervous system and suggest that a severe deficit in hippocampal-dependent learning need not be associated with reduced hippocampal long-term potentiation. PMID:8700840

  17. Seasonal variation of long-term potentiation at a central synapse in the medicinal leech.

    PubMed

    Grey, Kathryn B; Burrell, Brian D

    2011-08-01

    Long-term potentiation (LTP) is a persistent increase in synaptic transmission that is thought to contribute to a variety of adaptive processes including learning and memory. Although learning is known to undergo circannual variations, it is not known whether LTP undergoes similar changes despite the importance of LTP in learning and memory. Here we report that synapses in the CNS of the medicinal leech demonstrate seasonal variation in the capacity to undergo LTP following paired presynaptic and postsynaptic stimulation. LTP was observed during the April-October period, but no LTP was observed during the November-March period. Application of forskolin, a technique often used to produce chemical LTP, failed to elicit potentiation during the November-March period. Implementing stimulation patterns that normally result in long term depression (LTD) also failed to elicit any change in synaptic strength during the November-March period. These experiments indicate that LTP and LTD can be influenced by circannual rhythms and also suggest a seasonal influence on learning and memory.

  18. Seasonal variation of long-term potentiation at a central synapse in the medicinal leech

    PubMed Central

    Grey, Kathryn B.; Burrell, Brian D.

    2011-01-01

    SUMMARY Long-term potentiation (LTP) is a persistent increase in synaptic transmission that is thought to contribute to a variety of adaptive processes including learning and memory. Although learning is known to undergo circannual variations, it is not known whether LTP undergoes similar changes despite the importance of LTP in learning and memory. Here we report that synapses in the CNS of the medicinal leech demonstrate seasonal variation in the capacity to undergo LTP following paired presynaptic and postsynaptic stimulation. LTP was observed during the April–October period, but no LTP was observed during the November–March period. Application of forskolin, a technique often used to produce chemical LTP, failed to elicit potentiation during the November–March period. Implementing stimulation patterns that normally result in long term depression (LTD) also failed to elicit any change in synaptic strength during the November–March period. These experiments indicate that LTP and LTD can be influenced by circannual rhythms and also suggest a seasonal influence on learning and memory. PMID:21753047

  19. Inhibitory long-term potentiation underlies auditory conditioning of goldfish escape behaviour.

    PubMed

    Oda, Y; Kawasaki, K; Morita, M; Korn, H; Matsui, H

    1998-07-01

    Long-term potentiation (LTP), the increase in synaptic strength evoked by high-frequency stimulation, is often considered to be a cellular model for learning and memory. The validity of this model depends on the assumptions that physiological stimuli can induce LTP in vivo and that the resulting synaptic modifications correlate with behavioural changes. However, modifiable synapses are generally embedded deep in complex circuits. In contrast, the goldfish Mauthner (M)-cell and its afferent synapses are easily accessible for electrophysiological studies, and firing of this neuron is sufficient to trigger fast escape behaviour in response to sudden stimuli. We have previously shown that tetanic stimulation can induce LTP of the feedforward inhibitory synapses that control the excitability of the M-cell. Here we report that natural sensory stimulation can induce potentiation of this inhibitory connection that resembles the LTP induced by afferent tetanization. Furthermore, comparable acoustic stimulation produced a parallel decrease in the probability of the sound-evoked escape reflex. Thus we demonstrate for the first time, to our knowledge, a behavioural role for the long-term synaptic strengthening of inhibitory synapses.

  20. Long-term antibiotic delivery by chitosan-based composite coatings with bone regenerative potential

    NASA Astrophysics Data System (ADS)

    Ordikhani, F.; Simchi, A.

    2014-10-01

    Composite coatings with bone-bioactivity and drug-eluting capacity are considered as promising materials for titanium bone implants. In this work, drug-eluting chitosan-bioactive glass coatings were fabricated by a single-step electrophoretic deposition technique. Drug-loading and -releasing capacity of the composite coatings were carried out using the vancomycin antibiotic. Uniform coatings with a thickness of ∼55 μm containing 23.7 wt% bioactive glass particles and various amounts of the antibiotic (380-630 μg/cm2) were produced. The coatings were bioactive in terms of apatite-forming ability in simulated body fluid and showed favorable cell adhesion and growth. In vitro biological tests also indicated that the composite coatings had better cellular affinity than pristine chitosan coatings. The in vitro elution kinetics of the composite coating revealed an initial burst release of around 40% of the drug within the first elution step of 1 h and following by a continuous eluting over 4 weeks, revealing long-term drug-delivering potential. Antibacterial tests using survival assay against Gram-positive Staphylococcus aureus bacteria determined the effect of vancomycin release on reduction of infection risk. Almost no bacteria were survived on the coatings prepared from the EPD suspension containing ≥0.5 g/l vancomycin. The developed chitosan-based composite coatings with bone bioactivity and long-term drug-delivery ability may be potentially useful for metallic implants to reduce infection risk.

  1. Dendritic sodium spikes are required for long-term potentiation at distal synapses on hippocampal pyramidal neurons

    PubMed Central

    Kim, Yujin; Hsu, Ching-Lung; Cembrowski, Mark S; Mensh, Brett D; Spruston, Nelson

    2015-01-01

    Dendritic integration of synaptic inputs mediates rapid neural computation as well as longer-lasting plasticity. Several channel types can mediate dendritically initiated spikes (dSpikes), which may impact information processing and storage across multiple timescales; however, the roles of different channels in the rapid vs long-term effects of dSpikes are unknown. We show here that dSpikes mediated by Nav channels (blocked by a low concentration of TTX) are required for long-term potentiation (LTP) in the distal apical dendrites of hippocampal pyramidal neurons. Furthermore, imaging, simulations, and buffering experiments all support a model whereby fast Nav channel-mediated dSpikes (Na-dSpikes) contribute to LTP induction by promoting large, transient, localized increases in intracellular calcium concentration near the calcium-conducting pores of NMDAR and L-type Cav channels. Thus, in addition to contributing to rapid neural processing, Na-dSpikes are likely to contribute to memory formation via their role in long-lasting synaptic plasticity. DOI: http://dx.doi.org/10.7554/eLife.06414.001 PMID:26247712

  2. Wip1 phosphatase modulates both long-term potentiation and long-term depression through the dephosphorylation of CaMKII.

    PubMed

    He, Zhi-Yong; Hu, Wei-Yan; Zhang, Ming; Yang, Zara Zhuyun; Zhu, Hong-Mei; Xing, Da; Ma, Quan-Hong; Xiao, Zhi-Cheng

    2016-05-01

    Synaptic plasticity is an important mechanism that underlies learning and cognition. Protein phosphorylation by kinases and dephosphorylation by phosphatases play critical roles in the activity-dependent alteration of synaptic plasticity. In this study, we report that Wip1, a protein phosphatase, is essential for long-term potentiation (LTP) and long-term depression (LTD) processes. Wip1-deletion suppresses LTP and enhances LTD in the hippocampus CA1 area. Wip1 deficiency-induced aberrant elevation of CaMKII T286/287 and T305 phosphorylation underlies these dysfunctions. Moreover, we showed that Wip1 modulates CaMKII dephosphorylation. Wip1(-/-) mice exhibit abnormal GluR1 membrane expression, which could be reversed by the application of a CaMKII inhibitor, indicating that Wip1/CaMKII signaling is crucial for synaptic plasticity. Together, our results demonstrate that Wip1 phosphatase plays a vital role in regulating hippocampal synaptic plasticity by modulating the phosphorylation of CaMKII.

  3. A model of the mechanism of cooperativity and associativity of long-term potentiation in the hippocampus: a fundamental mechanism of associative memory and learning.

    PubMed

    Kitajima, T; Hara, K

    1991-01-01

    Long-Term Potentiation (LTP) has three properties: (1) input specificity, (2) cooperativity and (3) associativity. In a previous paper, we proposed an integrated model of the mechanisms of the induction and maintenance of LTP with input specificity. In this paper, a model of the mechanism of cooperative and associative LTP is described. According to computer simulations of the model, its mechanism is based on the spread of synaptic potentials. PMID:2049412

  4. Neonatal Immune Tolerance Induction to Allow Long-Term Studies With an Immunogenic Therapeutic Monoclonal Antibody in Mice.

    PubMed

    Piccand, Matthieu; Bessa, Juliana; Schick, Eginhard; Senn, Claudia; Bourquin, Carole; Richter, Wolfgang F

    2016-03-01

    The purpose of this study is to test the feasibility of neonatal immune tolerance induction in mice to enable long-term pharmacokinetic studies with immunogenic therapeutic monoclonal antibodies (mAb). Neonatal immune tolerance was induced by transfer of a mAb to neonatal mice via colostrum from nursing mother mice treated with two subcutaneous doses of a tolerogen starting within the first 24 h after delivery. Adalimumab and efalizumab were administered as tolerogens at various dose levels. Tolerance induction was evaluated in the offspring after reaching adulthood at 8 weeks of age. After a single intravenous injection of the same mAb as used for tolerance induction, the pharmacokinetics of the mAb and formation of anti-drug antibodies (ADA) in plasma were assessed using ELISA. Tolerance induction to adalimumab was achieved in a maternal dose-dependent manner. Adalimumab immune-tolerant offspring showed a slower adalimumab clearance (4.24 ± 0.32 mL/day/kg) as compared to the control group (12.09 ± 3.81 mL/day/kg). In the control group, accelerated clearance started 7 days after adalimumab dosing, whereas immune-tolerant offspring showed a log-linear terminal concentration-time course. In the offspring, the absence of predose ADA levels was indicative of successful tolerance induction. The second test compound efalizumab was not immunogenic in mice under our experimental conditions. Overall, the present study demonstrated the suitability of neonatal immune tolerance induction for a 4-week single dose study in adult mice with a human therapeutic mAb that is otherwise immunogenic in laboratory animals. PMID:26603888

  5. Neonatal Immune Tolerance Induction to Allow Long-Term Studies With an Immunogenic Therapeutic Monoclonal Antibody in Mice.

    PubMed

    Piccand, Matthieu; Bessa, Juliana; Schick, Eginhard; Senn, Claudia; Bourquin, Carole; Richter, Wolfgang F

    2016-03-01

    The purpose of this study is to test the feasibility of neonatal immune tolerance induction in mice to enable long-term pharmacokinetic studies with immunogenic therapeutic monoclonal antibodies (mAb). Neonatal immune tolerance was induced by transfer of a mAb to neonatal mice via colostrum from nursing mother mice treated with two subcutaneous doses of a tolerogen starting within the first 24 h after delivery. Adalimumab and efalizumab were administered as tolerogens at various dose levels. Tolerance induction was evaluated in the offspring after reaching adulthood at 8 weeks of age. After a single intravenous injection of the same mAb as used for tolerance induction, the pharmacokinetics of the mAb and formation of anti-drug antibodies (ADA) in plasma were assessed using ELISA. Tolerance induction to adalimumab was achieved in a maternal dose-dependent manner. Adalimumab immune-tolerant offspring showed a slower adalimumab clearance (4.24 ± 0.32 mL/day/kg) as compared to the control group (12.09 ± 3.81 mL/day/kg). In the control group, accelerated clearance started 7 days after adalimumab dosing, whereas immune-tolerant offspring showed a log-linear terminal concentration-time course. In the offspring, the absence of predose ADA levels was indicative of successful tolerance induction. The second test compound efalizumab was not immunogenic in mice under our experimental conditions. Overall, the present study demonstrated the suitability of neonatal immune tolerance induction for a 4-week single dose study in adult mice with a human therapeutic mAb that is otherwise immunogenic in laboratory animals.

  6. Long-Term Potentiation by Theta-Burst Stimulation Using Extracellular Field Potential Recordings in Acute Hippocampal Slices.

    PubMed

    Abrahamsson, Therese; Lalanne, Txomin; Watt, Alanna J; Sjöström, P Jesper

    2016-01-01

    This protocol describes how to carry out theta-burst long-term potentiation (LTP) with extracellular field recordings in acute rodent hippocampal slices. This method is relatively simple and noninvasive and provides a way to sample many neurons simultaneously, making it suitable for applications requiring higher throughput than whole-cell recording. PMID:27250947

  7. Proteolysis of cell adhesion molecules by serine proteases: a role in long term potentiation?

    PubMed

    Hoffman, K B; Martinez, J; Lynch, G

    1998-11-16

    Tissue plasminogen activator (tPA), a serine protease endogenous to hippocampal neurons, is shown to recognize a highly conserved sequence in the extracellular domain of cell adhesion molecules (CAMs). When added to brain homogenates, tPA generated a CAM fragment similar in size to that produced in hippocampal slices by brief periods of NMDA receptor stimulation. The serine protease inhibitor 4-(2-Aminoethyl)-benzenesulfonyl fluoride blocked the effects of tPA with an approximately 50% suppression at 250 microM. The inhibitor at this concentration had no evident effect on synaptic responses but caused long term potentiation to decay back to baseline over a 1 h period. These results suggest that extracellular breakdown of cell adhesion molecules initiated by NMDA receptors and mediated by serine proteases contributes to the formation of stable potentiation.

  8. Voluntary exercise does not enhance long-term potentiation in the adolescent female dentate gyrus.

    PubMed

    Titterness, A K; Wiebe, E; Kwasnica, A; Keyes, G; Christie, B R

    2011-06-01

    The hippocampus is a dynamic brain structure involved with learning and memory. Long-term potentiation (LTP) is a neuronal model of learning and memory and, in adult rodents, is enhanced by voluntary exercise (VEx). The current study sought to elucidate whether synaptic plasticity in the male and female adolescent hippocampus is augmented by VEx. Consistent with previous studies, VEx significantly enhanced LTP in adolescent males following weak and strong theta-burst stimulation. Despite running the same amount as males, however, VEx did not enhance LTP in females above non-runner females. Surprisingly, the exercise-induced enhancement to LTP in males was seen in the absence of a change in brain derived neurotrophic factor in the dentate gyrus (DG). These findings indicate that adolescent males and females are differentially sensitive to the potentiating effect of exercise on hippocampal synaptic plasticity.

  9. Impaired long-term potentiation-like cortical plasticity in presymptomatic genetic frontotemporal dementia.

    PubMed

    Benussi, Alberto; Cosseddu, Maura; Filareto, Ilaria; Dell'Era, Valentina; Archetti, Silvana; Sofia Cotelli, Maria; Micheli, Anna; Padovani, Alessandro; Borroni, Barbara

    2016-09-01

    Neurophysiological biomarkers were assessed using a transcranial magnetic stimulation multiparadigm approach in 13 presymptomatic (n = 13 Granulin) and 14 symptomatic (n = 11 Granulin, n = 3 C9orf72) subjects with a pathogenic mutation for frontotemporal dementia (FTD). Intracortical facilitation and long-term potentiation-like plasticity were impaired in presymptomatic carriers, compared to healthy controls, more than 15 years before expected symptom onset. In symptomatic carriers, a decrease in short-interval intracortical inhibition, compared to presymptomatic carriers, was found. In conclusion, these biomarkers could provide the footprints of specific physiopathological processes in the development of this disease and possibly support the diagnosis of autosomal-dominant FTD. Ann Neurol 2016;80:472-476. PMID:27438089

  10. Identification of compounds that potentiate CREB signaling as possible enhancers of long-term memory

    PubMed Central

    Xia, Menghang; Huang, Ruili; Guo, Vicky; Southall, Noel; Cho, Ming-Hsuang; Inglese, James; Austin, Christopher P.; Nirenberg, Marshall

    2009-01-01

    Many studies have implicated the cAMP Response Element Binding (CREB) protein signaling pathway in long-term memory. To identify small molecule enhancers of CREB activation of gene expression, we screened ≈73,000 compounds, each at 7–15 concentrations in a quantitative high-throughput screening (qHTS) format, for activity in cells by assaying CREB mediated β-lactamase reporter gene expression. We identified 1,800 compounds that potentiated CREB mediated gene expression, with potencies as low as 16 nM, comprising 96 structural series. Mechanisms of action were systematically determined, and compounds that affect phosphodiesterase 4, protein kinase A, and cAMP production were identified, as well as compounds that affect CREB signaling via apparently unidentified mechanisms. qHTS folowed by interrogation of pathway targets is an efficient paradigm for lead generation for chemical genomics and drug development. PMID:19196967

  11. Expression mechanisms underlying long-term potentiation: a postsynaptic view, 10 years on

    PubMed Central

    Granger, Adam J.; Nicoll, Roger A.

    2014-01-01

    This review focuses on the research that has occurred over the past decade which has solidified a postsynaptic expression mechanism for long-term potentiation (LTP). However, experiments that have suggested a presynaptic component are also summarized. It is argued that the pairing of glutamate uncaging onto single spines with postsynaptic depolarization provides the final and most elegant demonstration of a postsynaptic expression mechanism for NMDA receptor-dependent LTP. The fact that the magnitude of this LTP is similar to that evoked by pairing synaptic stimulation and depolarization leaves little room for a substantial presynaptic component. Finally, recent data also require a revision in our thinking about the way AMPA receptors (AMPARs) are recruited to the postsynaptic density during LTP. This recruitment is independent of subunit type, but does require an adequate reserve pool of extrasynaptic receptors. PMID:24298139

  12. The expression of long-term potentiation: reconciling the preists and the postivists

    PubMed Central

    MacDougall, Matthew J.; Fine, Alan

    2014-01-01

    Long-term potentiation (LTP) of excitatory synaptic transmission in the hippocampus has been investigated in great detail over the past 40 years. Where and how LTP is actually expressed, however, remain controversial issues. Considerable evidence has been offered to support both pre- and postsynaptic contributions to LTP expression. Though it is widely held that postsynaptic expression mechanisms are the primary contributors to LTP expression, evidence for that conclusion is amenable to alternative explanations. Here, we briefly review some key contributions to the ‘locus’ debate and describe data that support a dominant role for presynaptic mechanisms. Recognition of the state-dependency of expression mechanisms, and consideration of the consequences of the spatial relationship between postsynaptic glutamate receptors and presynaptic vesicular release sites, lead to a model that may reconcile views from both sides of the synapse. PMID:24298138

  13. The expression of long-term potentiation: reconciling the preists and the postivists.

    PubMed

    MacDougall, Matthew J; Fine, Alan

    2014-01-01

    Long-term potentiation (LTP) of excitatory synaptic transmission in the hippocampus has been investigated in great detail over the past 40 years. Where and how LTP is actually expressed, however, remain controversial issues. Considerable evidence has been offered to support both pre- and postsynaptic contributions to LTP expression. Though it is widely held that postsynaptic expression mechanisms are the primary contributors to LTP expression, evidence for that conclusion is amenable to alternative explanations. Here, we briefly review some key contributions to the 'locus' debate and describe data that support a dominant role for presynaptic mechanisms. Recognition of the state-dependency of expression mechanisms, and consideration of the consequences of the spatial relationship between postsynaptic glutamate receptors and presynaptic vesicular release sites, lead to a model that may reconcile views from both sides of the synapse.

  14. Increased Learning and Brain Long-Term Potentiation in Aged Mice Lacking DNA Polymerase μ

    PubMed Central

    Lucas, Daniel; Delgado-García, José M.; Escudero, Beatriz; Albo, Carmen; Aza, Ana; Acín-Pérez, Rebeca; Torres, Yaima; Moreno, Paz; Enríquez, José Antonio; Samper, Enrique; Blanco, Luis; Fairén, Alfonso

    2013-01-01

    A definitive consequence of the aging process is the progressive deterioration of higher cognitive functions. Defects in DNA repair mechanisms mostly result in accelerated aging and reduced brain function. DNA polymerase µ is a novel accessory partner for the non-homologous end-joining DNA repair pathway for double-strand breaks, and its deficiency causes reduced DNA repair. Using associative learning and long-term potentiation experiments, we demonstrate that Polµ−/− mice, however, maintain the ability to learn at ages when wild-type mice do not. Expression and biochemical analyses suggest that brain aging is delayed in Polµ−/− mice, being associated with a reduced error-prone DNA oxidative repair activity and a more efficient mitochondrial function. This is the first example in which the genetic ablation of a DNA-repair function results in a substantially better maintenance of learning abilities, together with fewer signs of brain aging, in old mice. PMID:23301049

  15. Induction of long-term immunity against respiratory syncytial virus glycoprotein by an osmotic polymeric nanocarrier.

    PubMed

    Firdous, Jannatul; Islam, Mohammad Ariful; Park, Sung-Moo; Cheon, In-Su; Shim, Byoung-Shik; Yoon, Hyo-Shin; Song, Manki; Chang, Jun; Choi, Yun-Jaie; Park, Yeong-Min; Boraschi, Diana; Han, Seung-Hyun; Cho, Chong-Su; Yun, Cheol-Heui

    2014-11-01

    Respiratory syncytial virus (RSV) is one of the most common causes of viral deaths in infants worldwide, yet no effective vaccines are available. Here, we report an osmotically active polysaccharide-based polysorbitol transporter (PST) prepared from sorbitol diacrylate and low-molecular-weight polyethylenimine (PEI) showing a potent, yet safe, adjuvant activity and acting as an effective delivery tool for RSV glycoprotein (RGp) antigen. PST showed no toxicity in vitro or in vivo, unlike PEI and the well-known experimental mucosal adjuvant cholera toxin (CT). PST formed nano-sized complexes with RGp by simple mixing, without affecting antigenic stability. The complexes exhibited negative surface charges that made them highly efficient in the selective activation of phagocytic cells and enhancement of phagocytic uptake. This resulted in an improved cytokine production and in the significant augmentation of RGp-specific antibody production, which persisted for over 200 days. Interestingly, PST/RGp enhanced phagocytic uptake owing to the osmotic property of PST and its negative zeta potential, suggesting that PST could selectively stimulate phagocytic cells, thereby facilitating a long-lived antigen-specific immune response, which was presumably further enhanced by the polysaccharide properties of PST. PMID:25110285

  16. Involvement of Microglia Activation in the Lead Induced Long-Term Potentiation Impairment

    PubMed Central

    Wang, Wen; Shen, Xue-Feng; Che, Hong-Lei; Guo, Yan-Yan; Zhao, Ming-Gao; Chen, Jing-Yuan; Luo, Wen-Jing

    2012-01-01

    Exposure of Lead (Pb), a known neurotoxicant, can impair spatial learning and memory probably via impairing the hippocampal long-term potentiation (LTP) as well as hippocampal neuronal injury. Activation of hippocampal microglia also impairs spatial learning and memory. Thus, we raised the hypothesis that activation of microglia is involved in the Pb exposure induced hippocampal LTP impairment and neuronal injury. To test this hypothesis and clarify its underlying mechanisms, we investigated the Pb-exposure on the microglia activation, cytokine release, hippocampal LTP level as well as neuronal injury in in vivo or in vitro model. The changes of these parameters were also observed after pretreatment with minocycline, a microglia activation inhibitor. Long-term low dose Pb exposure (100 ppm for 8 weeks) caused significant reduction of LTP in acute slice preparations, meanwhile, such treatment also significantly increased hippocampal microglia activation as well as neuronal injury. In vitro Pb-exposure also induced significantly increase of microglia activation, up-regulate the release of cytokines including tumor necrosis factor-alpha (TNF-α), interleukin-1β (IL-1β) and inducible nitric oxide synthase (iNOS) in microglia culture alone as well as neuronal injury in the co-culture with hippocampal neurons. Inhibiting the microglia activation with minocycline significantly reversed the above-mentioned Pb-exposure induced changes. Our results showed that Pb can cause microglia activation, which can up-regulate the level of IL-1β, TNF-α and iNOS, these proinflammatory factors may cause hippocampal neuronal injury as well as LTP deficits. PMID:22952811

  17. Steatohepatitis secondary to long-term glucocorticoid treatment for congenital adrenal hyperplasia: a potential diagnostic pitfall.

    PubMed

    Ding, Xianzhong; Thung, Swan N; Grewal, Priya

    2013-11-01

    A 24-year-old woman with congenital adrenal hyperplasia (CAH) was referred for evaluation of elevated liver enzyme activities over the preceding 6 months. The patient was diagnosed with CAH at the age 12 when she presented with irregular menses and hirsutism. Since then, she had been on dexamethasone to maintain a normal menstrual cycle and prevent hirsutism and acne. She had no history of chronic liver disease and drank alcohol socially. An extensive workup for other treatable causes of liver disease was unrevealing. Therefore, a liver biopsy was performed, which revealed extensive ballooned degenerative hepatocytes containing Mallory-Denk hyalines. The ballooned hepatocytes were located predominantly in centrilobular areas and without any accompanying steatosis. Even though the histopathologic features are most compatible with alcoholic and/or nonalcoholic steatohepatitis, it was not supported by the patient's medical history and clinical presentation. The patient had a normal body mass index and only occasional alcohol use. Based on the biopsy finding and clinical presentation, we postulated that the abnormal liver enzyme and pathological features seen on the liver biopsy were secondary to CAH and long-term use of glucocorticoid. A few studies have shown that patients with CAH often develop metabolic abnormalities and insulin resistance, particularly women treated with glucocorticoid for several years. To our knowledge, this is the first report describing steatohepatitis secondary to CAH and prolonged glucocorticoid treatment. It is important to be aware that steatohepatitis can develop in these patients due to long-term glucocorticoid use and potentially lead to progressive liver damage. Furthermore, in patients with CAH who develop abnormal liver enzyme activities a liver biopsy is warranted to assess for steatohepatitis and any associated fibrosis. If indeed fibrosis is already present, a consultation with the endocrinologist should be undertaken in an effort

  18. Activation of Muscarinic M1 Acetylcholine Receptors Induces Long-Term Potentiation in the Hippocampus.

    PubMed

    Dennis, Siobhan H; Pasqui, Francesca; Colvin, Ellen M; Sanger, Helen; Mogg, Adrian J; Felder, Christian C; Broad, Lisa M; Fitzjohn, Steve M; Isaac, John T R; Mellor, Jack R

    2016-01-01

    Muscarinic M1 acetylcholine receptors (M1Rs) are highly expressed in the hippocampus, and their inhibition or ablation disrupts the encoding of spatial memory. It has been hypothesized that the principal mechanism by which M1Rs influence spatial memory is by the regulation of hippocampal synaptic plasticity. Here, we use a combination of recently developed, well characterized, selective M1R agonists and M1R knock-out mice to define the roles of M1Rs in the regulation of hippocampal neuronal and synaptic function. We confirm that M1R activation increases input resistance and depolarizes hippocampal CA1 pyramidal neurons and show that this profoundly increases excitatory postsynaptic potential-spike coupling. Consistent with a critical role for M1Rs in synaptic plasticity, we now show that M1R activation produces a robust potentiation of glutamatergic synaptic transmission onto CA1 pyramidal neurons that has all the hallmarks of long-term potentiation (LTP): The potentiation requires NMDA receptor activity and bi-directionally occludes with synaptically induced LTP. Thus, we describe synergistic mechanisms by which acetylcholine acting through M1Rs excites CA1 pyramidal neurons and induces LTP, to profoundly increase activation of CA1 pyramidal neurons. These features are predicted to make a major contribution to the pro-cognitive effects of cholinergic transmission in rodents and humans. PMID:26472558

  19. Long-term variability of the thunderstorm and hail potential in Europe

    NASA Astrophysics Data System (ADS)

    Mohr, Susanna; Kunz, Michael; Speidel, Johannes; Piper, David

    2016-04-01

    Severe thunderstorms and associated hazardous weather events such as hail frequently cause considerable damage to buildings, crops, and automobiles, resulting in large monetary costs in many parts of Europe and the world. To relate single extreme hail events to the historic context and to estimate their return periods and possible trends related to climate change, long-term statistics of hail events are required. Due to the local-scale nature of hail and a lack of suitable observation systems, however, hailstorms are not captured reliably and comprehensively for a long period of time. In view of this fact, different proxies (indirect climate data) obtained from sounding stations and regional climate models can be used to infer the probability and intensity of thunderstorms or hailstorms. In contrast to direct observational data, such proxies are available homogeneously over a long time period. The aim of the study is to investigate the potential for severe thunderstorms and their changes over past decades. Statistical analyses of sounding data show that the convective potential over the past 20 - 30 years has significantly increased over large parts of Central Europe, making severe thunderstorms more likely. A similar picture results from analyses of weather types that are most likely associated with damaging hailstorms. These weather patterns have increased, even if only slightly but nevertheless statistically significantly, in the time period from 1971 to 2000. To improve the diagnostics of hail events in regional climate models, a logistic hail model has been developed by means of a multivariate analysis method. The model is based on a combination of appropriate hail-relevant meteorological parameters. The output of the model is a new index that estimates the potential of the atmosphere for hailstorm development, referred to as potential hail index (PHI). Applied to a high-resolved reanalysis run for Europe driven by NCEP/NCAR1, long-term changes of the PHI for

  20. The Association between Long-Term Care Setting and Potentially Preventable Hospitalizations among Older Dual Eligibles

    PubMed Central

    Wysocki, Andrea; Kane, Robert L; Golberstein, Ezra; Dowd, Bryan; Lum, Terry; Shippee, Tetyana

    2014-01-01

    Objective To compare the probability of experiencing a potentially preventable hospitalization (PPH) between older dual eligible Medicaid home and community-based service (HCBS) users and nursing home residents. Data Sources Three years of Medicaid and Medicare claims data (2003–2005) from seven states, linked to area characteristics from the Area Resource File. Study Design A primary diagnosis of an ambulatory care sensitive condition on the inpatient hospital claim was used to identify PPHs. We used inverse probability of treatment weighting to mitigate the potential selection of HCBS versus nursing home use. Principal Findings The most frequent conditions accounting for PPHs were the same among the HCBS users and nursing home residents and included congestive heart failure, pneumonia, chronic obstructive pulmonary disease, urinary tract infection, and dehydration. Compared to nursing home residents, elderly HCBS users had an increased probability of experiencing both a PPH and a non-PPH. Conclusions HCBS users’ increased probability for potentially and non-PPHs suggests a need for more proactive integration of medical and long-term care. PMID:24628471

  1. Long-term climate change mitigation potential with organic matter management on grasslands.

    PubMed

    Ryals, Rebecca; Hartman, Melannie D; Parton, William J; DeLonge, Marcia S; Silver, Whendee L

    2015-03-01

    Compost amendments to grasslands have been proposed as a strategy to mitigate climate change through carbon (C) sequestration, yet little research exists exploring the net mitigation potential or the long-term impacts of this strategy. We used field data and the DAYCENT biogeochemical model to investigate the climate change mitigation potential of compost amendments to grasslands in California, USA. The model was used to test ecosystem C and greenhouse gas responses to a range of compost qualities (carbon to nitrogen [C:N] ratios of 11.1, 20, or 30) and application rates (single addition of 14 Mg C/ha or 10 annual additions of 1.4 Mg C · ha(-1) · yr(-1)). The model was parameterized using site-specific weather, vegetation, and edaphic characteristics and was validated by comparing simulated soil C, nitrous oxide (N2O), methane (CH4), and carbon dioxide (CO2) fluxes, and net primary production (NPP) with three years of field data. All compost amendment scenarios led to net greenhouse gas sinks that persisted for several decades. Rates of climate change mitigation potential ranged from 130 ± 3 g to 158 ± 8 g CO2-eq · m(-2) ·yr(-1) (where "eq" stands for "equivalents") when assessed over a 10-year time period and 63 ± 2 g to 84 ± 10 g CO2- eq · m(-2) · yr(-1) over a 30-year time period. Both C storage and greenhouse gas emissions increased rapidly following amendments. Compost amendments with lower C:N led to higher C sequestration rates over time. However, these soils also experienced greater N20 fluxes. Multiple smaller compost additions resulted in similar cumulative C sequestration rates, albeit with a time lag, and lower cumulative N2O emissions. These results identify a trade-off between maximizing C sequestration and minimizing N2O emissions following amendments, and suggest that compost additions to grassland soils can have a long-term impact on C and greenhouse gas dynamics that contributes to climate change mitigation. PMID:26263673

  2. Glycine blocks long-term potentiation of GABAergic synapses in the ventral tegmental area.

    PubMed

    Guan, Y-Z; Ye, J-H

    2016-03-24

    The mesocorticolimbic dopamine system, originating in the ventral tegmental area (VTA) is normally constrained by GABA-mediated synaptic inhibition. Accumulating evidence indicates that long-term potentiation of GABAergic synapses (LTPGABA) in VTA dopamine neurons plays an important role in the actions of drugs of abuse, including ethanol. We previously showed that a single infusion of glycine into the VTA of rats strongly reduces ethanol intake for 24h. In the current study, we examined the effect of glycine on the electrophysiological activities of putative dopamine VTA neurons in midbrain slices from ethanol-naïve rats. We report here that a 15-min exposure to 10 μM glycine prevented trains of high-frequency stimulation (HFS) from producing LTPGABA, which was rescued by the glycine receptor (GlyR) antagonist strychnine. Glycine also concentration-dependently decreased the frequency of spontaneous excitatory postsynaptic currents (sEPSCs). By contrast, glycine pretreatment did not prevent potentiation of inhibitory postsynaptic currents (IPSCs) during a continuous exposure to the nitric oxide (NO) donor, SNAP (S-nitroso-N-acetylpenicillamine), or a brief exposure to 10 μM glycine and 10 μM NMDA (N-methyl-D-aspartate), an agonist of NMDA-type glutamate receptors. Thus, the blockade of LTPGABA by glycine is probably resulted from suppressing glutamate release by activating the GlyRs on the glutamatergic terminals. This effect of glycine may contribute to the reduction in ethanol intake induced by intra-VTA glycine observed in vivo.

  3. Circadian rhythm modulates long-term potentiation induced at CA1 in rat hippocampal slices.

    PubMed

    Nakatsuka, Hiroki; Natsume, Kiyohisa

    2014-03-01

    Circadian rhythm affects neuronal plasticity. Consistent with this, some forms of synaptic long-term potentiation (LTP) are modulated by the light/dark cycle (LD cycle). For example, this type of modulation is observed in hippocampal slices. In rodents, which are nocturnal, LTP is usually facilitated in the dark phase, but the rat hippocampal CA1 is an exception. The reason why LTP in the dark phase is suppressed in CA1 remains unknown. Previously, LTP was induced with high-frequency stimulation. In this study, we found that in the dark phase, theta-burst stimulation-induced LTP is indeed facilitated in CA1, similar to other regions in the rodent brain. Population excitatory postsynaptic potentials (pEPSP)-LTP and population spikes (PS)-LTP were recorded at CA1. The magnitude of PS-LTP in dark-phase slices was significantly larger than in light-phase slices, while that of pEPSP-LTP was unchanged. Using antidromic-orthodromic stimulation, we found that recurrent inhibition is suppressed in the dark phase. Local gabazine-application to stratum pyramidale in light-phase slices mimicked this disinhibition and facilitated LTP in dark-phase slices. These results suggest that the disinhibition of a GABAA recurrent inhibitory network can be induced in the dark phase, thereby facilitating LTP.

  4. Possible involvement of plasmin in long-term potentiation of rat hippocampal slices.

    PubMed

    Mizutani, A; Saito, H; Matsuki, N

    1996-11-11

    Effects of proteases and protease inhibitors on generation of long-term potentiation (LTP) were investigated in the CA1 and dentate regions of rat hippocampus. Plasmin, a serine protease, and its precursor plasminogen significantly enhanced short-term potentiation (STP) induced by a weak tetanic stimulation, without affecting basal responses. The STP-enhancing effect of plasmin disappeared by concomitant perfusion of alpha 2-antiplasmin, an endogenous plasmin inhibitor. Other proteases, such as thrombin, trypsin and cathepsin B, did not affect STP. On the other hand, alpha 2-antiplasmin and leupeptin significantly attenuated LTP induced by a strong tetanus though plasminogen or plasmin itself did not influence LTP. Furthermore, plasminogen and plasmin did not affect NMDA receptor-mediated synaptic responses in the absence of extracellular Mg2+. These results suggest that endogenous plasmin is involved in the mechanism of LTP in CA1 and dentate regions of rat hippocampus and that the STP-enhancing effect of plasmin is independent of NMDA receptors.

  5. Overexpression of Protein Kinase Mζ in the Hippocampus Enhances Long-Term Potentiation and Long-Term Contextual But Not Cued Fear Memory in Rats

    PubMed Central

    Fernández-Fernández, Diego; Lamla, Thorsten; Rosenbrock, Holger

    2016-01-01

    The persistently active protein kinase Mζ (PKMζ) has been found to be involved in the formation and maintenance of long-term memory. Most of the studies investigating PKMζ, however, have used either putatively unselective inhibitors or conventional knock-out animal models in which compensatory mechanisms may occur. Here, we overexpressed an active form of PKMζ in rat hippocampus, a structure highly involved in memory formation, and embedded in several neural networks. We investigated PKMζ's influence on synaptic plasticity using electrophysiological recordings of basal transmission, paired pulse facilitation, and LTP and combined this with behavioral cognitive experiments addressing formation and retention of both contextual memory during aversive conditioning and spatial memory during spontaneous exploration. We demonstrate that hippocampal slices overexpressing PKMζ show enhanced basal transmission, suggesting a potential role of PKMζ in postsynaptic AMPAR trafficking. Moreover, the PKMζ-overexpressing slices augmented LTP and this effect was not abolished by protein-synthesis blockers, indicating that PKMζ induces enhanced LTP formation in a protein-synthesis-independent manner. In addition, we found selectively enhanced long-term memory for contextual but not cued fear memory, underlining the theory of the hippocampus' involvement in the contextual aspect of aversive reinforced tasks. Memory for spatial orientation during spontaneous exploration remained unaltered, suggesting that PKMζ may not affect the neural circuits underlying spontaneous tasks that are different from aversive tasks. In this study, using an overexpression strategy as opposed to an inhibitor-based approach, we demonstrate an important modulatory role of PKMζ in synaptic plasticity and selective memory processing. SIGNIFICANCE STATEMENT Most of the literature investigating protein kinase Mζ (PKMζ) used inhibitors with selectivity that has been called into question or conventional

  6. Both NR2A and NR2B Subunits of the NMDA Receptor Are Critical for Long-Term Potentiation and Long-Term Depression in the Lateral Amygdala of Horizontal Slices of Adult Mice

    ERIC Educational Resources Information Center

    Muller, Tobias; Albrecht, Doris; Gebhardt, Christine

    2009-01-01

    The lateral nucleus of the amygdala (LA) is implicated in emotional and social behaviors. We recently showed that in horizontal brain slices, activation of NMDA receptors (NMDARs) is a requirement for persistent synaptic alterations in the LA, such as long-term potentiation (LTP) and long-term depression (LTD). In the LA, NR2A- and NR2B-type NMDRs…

  7. Long-term potentiation in the neonatal rat barrel cortex in vivo.

    PubMed

    An, Shuming; Yang, Jenq-Wei; Sun, Haiyan; Kilb, Werner; Luhmann, Heiko J

    2012-07-11

    Long-term potentiation (LTP) is important for the activity-dependent formation of early cortical circuits. In the neonatal rodent barrel cortex, LTP has been studied only in vitro. We combined voltage-sensitive dye imaging with extracellular multielectrode recordings to study whisker stimulation-induced LTP in the whisker-to-barrel cortex pathway of the neonatal rat barrel cortex in vivo. Single whisker stimulation at 2 Hz for 10 min induced an age-dependent expression of LTP in postnatal day (P) 0 to P14 rats, with the strongest expression of LTP at P3-P5. The magnitude of LTP was largest in the activated barrel-related column, smaller in the surrounding septal region, and no LTP could be observed in the neighboring barrel. Current source density analyses revealed an LTP-associated increase of synaptic current sinks in layer IV/lower layer II/III at P3-P5 and in the cortical plate/upper layer V at P0-P1. Our study demonstrates for the first time an age-dependent and spatially confined LTP in the barrel cortex of the newborn rat in vivo.

  8. Isolated Primary Blast Inhibits Long-Term Potentiation in Organotypic Hippocampal Slice Cultures.

    PubMed

    Vogel, Edward W; Effgen, Gwen B; Patel, Tapan P; Meaney, David F; Bass, Cameron R Dale; Morrison, Barclay

    2016-04-01

    Over the last 13 years, traumatic brain injury (TBI) has affected over 230,000 U.S. service members through the conflicts in Iraq and Afghanistan, mostly as a result of exposure to blast events. Blast-induced TBI (bTBI) is multi-phasic, with the penetrating and inertia-driven phases having been extensively studied. The effects of primary blast injury, caused by the shockwave interacting with the brain, remain unclear. Earlier in vivo studies in mice and rats have reported mixed results for primary blast effects on behavior and memory. Using a previously developed shock tube and in vitro sample receiver, we investigated the effect of isolated primary blast on the electrophysiological function of rat organotypic hippocampal slice cultures (OHSC). We found that pure primary blast exposure inhibited long-term potentiation (LTP), the electrophysiological correlate of memory, with a threshold between 9 and 39 kPa·ms impulse. This deficit occurred well below a previously identified threshold for cell death (184 kPa·ms), supporting our previously published finding that primary blast can cause changes in brain function in the absence of cell death. Other functional measures such as spontaneous activity, network synchronization, stimulus-response curves, and paired-pulse ratios (PPRs) were less affected by primary blast exposure, as compared with LTP. This is the first study to identify a tissue-level tolerance threshold for electrophysiological changes in neuronal function to isolated primary blast.

  9. The reemergence of long-term potentiation in aged Alzheimer’s disease mouse model

    PubMed Central

    Huh, Seonghoo; Baek, Soo-Ji; Lee, Kyung-Hwa; Whitcomb, Daniel J.; Jo, Jihoon; Choi, Seong-Min; Kim, Dong Hyun; Park, Man-Seok; Lee, Kun Ho; Kim, Byeong C.

    2016-01-01

    Mouse models of Alzheimer’s disease (AD) have been developed to study the pathophysiology of amyloid β protein (Aβ) toxicity, which is thought to cause severe clinical symptoms such as memory impairment in AD patients. However, inconsistencies exist between studies using these animal models, specifically in terms of the effects on synaptic plasticity, a major cellular model of learning and memory. Whereas some studies find impairments in plasticity in these models, others do not. We show that long-term potentiation (LTP), in the CA1 region of hippocampal slices from this mouse, is impared at Tg2576 adult 6–7 months old. However, LTP is inducible again in slices taken from Tg2576 aged 14–19 months old. In the aged Tg2576, we found that the percentage of parvalbumin (PV)-expressing interneurons in hippocampal CA1-3 region is significantly decreased, and LTP inhibition or reversal mediated by NRG1/ErbB signaling, which requires ErbB4 receptors in PV interneurons, is impaired. Inhibition of ErbB receptor kinase in adult Tg2576 restores LTP but impairs depotentiation as shown in aged Tg2576. Our study suggests that hippocampal LTP reemerges in aged Tg2576. However, this reemerged LTP is an insuppressible form due to impaired NRG1/ErbB signaling, possibly through the loss of PV interneurons. PMID:27377368

  10. Pharmacological activation of CB1 receptor modulates long term potentiation by interfering with protein synthesis.

    PubMed

    Navakkode, Sheeja; Korte, Martin

    2014-04-01

    Cognitive impairment is one of the most important side effects associated with cannabis drug abuse, as well as the serious issue concerning the therapeutic use of cannabinoids. Cognitive impairments and neuropsychiatric symptoms are caused by early synaptic dysfunctions, such as loss of synaptic connections in different brain structures including the hippocampus, a region that is believed to play an important role in certain forms of learning and memory. We report here that metaplastic priming of synapses with a cannabinoid type 1 receptor (CB1 receptor) agonist, WIN55,212-2 (WIN55), significantly impaired long-term potentiation in the apical dendrites of CA1 pyramidal neurons. Interestingly, the CB1 receptor exerts its effect by altering the balance of protein synthesis machinery towards higher protein production. Therefore the activation of CB1 receptor, prior to strong tetanization, increased the propensity to produce new proteins. In addition, WIN55 priming resulted in the expression of late-LTP in a synaptic input that would have normally expressed early-LTP, thus confirming that WIN55 priming of LTP induces new synthesis of plasticity-related proteins. Furthermore, in addition to the effects on protein translation, WIN55 also induced synaptic deficits due to the ability of CB1 receptors to inhibit the release of acetylcholine, mediated by both muscarinic and nicotinic acetylcholine receptors. Taken together this supports the notion that the modulation of cholinergic activity by CB1 receptor activation is one mechanism that regulates the synthesis of plasticity-related proteins.

  11. Long-term potentiation decay and memory loss are mediated by AMPAR endocytosis.

    PubMed

    Dong, Zhifang; Han, Huili; Li, Hongjie; Bai, Yanrui; Wang, Wei; Tu, Man; Peng, Yan; Zhou, Limin; He, Wenting; Wu, Xiaobin; Tan, Tao; Liu, Mingjing; Wu, Xiaoyan; Zhou, Weihui; Jin, Wuyang; Zhang, Shu; Sacktor, Todd Charlton; Li, Tingyu; Song, Weihong; Wang, Yu Tian

    2015-01-01

    Long-term potentiation (LTP) of synaptic strength between hippocampal neurons is associated with learning and memory, and LTP dysfunction is thought to underlie memory loss. LTP can be temporally and mechanistically classified into decaying (early-phase) LTP and nondecaying (late-phase) LTP. While the nondecaying nature of LTP is thought to depend on protein synthesis and contribute to memory maintenance, little is known about the mechanisms and roles of decaying LTP. Here, we demonstrated that inhibiting endocytosis of postsynaptic α-amino-3-hydroxy-5-methyl-isoxazole-4-propionic acid receptors (AMPARs) prevents LTP decay, thereby converting it into nondecaying LTP. Conversely, restoration of AMPAR endocytosis by inhibiting protein kinase Mζ (PKMζ) converted nondecaying LTP into decaying LTP. Similarly, inhibition of AMPAR endocytosis prolonged memory retention in normal animals and reduced memory loss in a murine model of Alzheimer's disease. These results strongly suggest that an active process that involves AMPAR endocytosis mediates the decay of LTP and that inhibition of this process can prolong the longevity of LTP as well as memory under both physiological and pathological conditions.

  12. Effect of intermittent hypoxia on long-term potentiation in rat hippocampal slices.

    PubMed

    Payne, Ralphiel S; Goldbart, Aviv; Gozal, David; Schurr, Avital

    2004-12-17

    Intermittent hypoxia (IH) during sleep has been shown to induce apoptosis in a time-dependent manner and spatial learning deficits in adult rats. Recently, we have demonstrated that IH induced significant decreases in Ser-133-phosphorylated cAMP-response element-binding protein (pCREB) without changes in total CREB. The expression of cleaved caspase 3 in the hippocampal CA1, a marker of apoptosis, peaked at 3 days of IH and returned to normoxic values at 14 days of IH. In addition, biphasic changes in spatial task learning were correlated with the CREB phosphorylation time course. In the present study, the rat hippocampal slice preparation was used to evaluate the ability to induce and maintain a CA1 population spike long-term potentiation (PS-LTP) in room air (RA)-maintained and IH-exposed rats. A significant decrease in the ability to sustain PS-LTP for 15 min in slices prepared from IH-exposed rats for either 3 days (34% of total) or 7 days (51% of total) as compared to slices prepared from RA-maintained rats (76% of total) was observed. These results suggest that the diminishment in the ability of neuronal tissue to express and sustain PS-LTP is correlated with previously reported biphasic changes in CREB phosphorylation and programmed cell death. PMID:15542074

  13. The role of endosomal-recycling in long-term potentiation.

    PubMed

    Kelly, Eoin E; Horgan, Conor P; McCaffrey, Mary W; Young, Paul

    2011-01-01

    Long-term potentiation (LTP) defines persistent increases in neurotransmission strength at synapses that are triggered by specific patterns of neuronal activity. LTP, the most widely accepted molecular model for learning, is best characterised at glutamatergic synapses on dendritic spines. In this context, LTP involves increases in dendritic spine size and the insertion of glutamate receptors into the post-synaptic spine membrane, which together boost post-synaptic responsiveness to neurotransmitters. In dendrites, the material required for LTP is sourced from an organelle termed the endosomal-recycling compartment (ERC), which is localised to the base of dendritic spines. When LTP is induced, material derived from the recycling compartment, which contains α-amino-3-hydroxy-5-methyl-4-isoxazole propionate-type glutamate receptors (AMPARs), is mobilised into dendritic spines feeding the increased need for receptors and membrane at the spine neck and head. In this review, we discuss the importance of endosomal-recycling and the role of key proteins which control these processes in the context of LTP. PMID:20820847

  14. Short-term plasticity and long-term potentiation mimicked in single inorganic synapses

    NASA Astrophysics Data System (ADS)

    Ohno, Takeo; Hasegawa, Tsuyoshi; Tsuruoka, Tohru; Terabe, Kazuya; Gimzewski, James K.; Aono, Masakazu

    2011-08-01

    Memory is believed to occur in the human brain as a result of two types of synaptic plasticity: short-term plasticity (STP) and long-term potentiation (LTP; refs , , , ). In neuromorphic engineering, emulation of known neural behaviour has proven to be difficult to implement in software because of the highly complex interconnected nature of thought processes. Here we report the discovery of a Ag2S inorganic synapse, which emulates the synaptic functions of both STP and LTP characteristics through the use of input pulse repetition time. The structure known as an atomic switch, operating at critical voltages, stores information as STP with a spontaneous decay of conductance level in response to intermittent input stimuli, whereas frequent stimulation results in a transition to LTP. The Ag2S inorganic synapse has interesting characteristics with analogies to an individual biological synapse, and achieves dynamic memorization in a single device without the need of external preprogramming. A psychological model related to the process of memorizing and forgetting is also demonstrated using the inorganic synapses. Our Ag2S element indicates a breakthrough in mimicking synaptic behaviour essential for the further creation of artificial neural systems that emulate characteristics of human memory.

  15. Exposure of mouse to high gravitation forces induces long-term potentiation in the hippocampus.

    PubMed

    Ishii, Masamitsu; Tomizawa, Kazuhito; Matsushita, Masayuki; Matsui, Hideki

    2004-06-01

    The central nervous system is highly plastic and has been shown to undergo both transient and chronic adaptive changes in response to environmental influences. The purpose of this study was to investigate the effect of hypergravic field on long-term potentiation (LTP) in the mouse hippocampus. Exposure of mice to 4G fields for 48 h had no effect on input-output coupling during extracellular stimulation of Schaffer collaterals and paired pulse facilitation, suggesting that the hypergravic exposure had no detrimental effect on basal neurotransmission in the hippocampus. However, the exposure to 4G fields for 48 h significantly induced LTP compared with the control mouse hippocampus. In contrast, no significant changes of late-phase LTP (L-LTP) were found in the hippocampi of mice exposed to the hypergravic field. Exposure of mice to 4G fields for 48 h enhanced AMPA receptor phosphorylation but not cyclic AMP-responsive element binding protein (CREB) phosphorylation. These results suggest that exposure to hyperdynamic fields influences the synaptic plasticity in the hippocampus.

  16. Effects of hyperdynamic fields on input-output relationships and long-term potentiation in the rat hippocampus.

    PubMed

    Guinan, M J; Horowitz, J M; Fuller, C A

    1998-10-01

    The effects of a 2G force environment on synaptic plasticity were examined in the rat hippocampus. Field potentials from neurons in the CA1 pyramidal cell layer were evoked by stimulation of the afferent Schaffer collateral/commissural fibers in an in vitro slice preparation. Input-output (I-O) relationships of the circuit were determined before and after tetanizing stimuli given to induce long term potentiation (LTP), a form of neural plasticity. I-O curves from animals exposed to 2G via centrifugation for either 2 or 14 days were not different from those obtained in control (1G) animals. Similarly, induction of LTP was equivalent in all groups, showing increases in maximum amplitude, slope and midpoint response of the fitted Boltzmann functions compared to un-tetanized controls. Comparison of slices from dorsal and ventral hippocampus showed the location of the slice had no effect of LTP expression. We conclude that, in contrast to other reports of functional changes in the central nervous system under altered force environments, cellular mechanisms of synaptic plasticity, which may underlie learning and memory, are preserved in the hippocampus. PMID:11541900

  17. Effects of high power microwave pulses on synaptic transmission and long term potentiation in hippocampus.

    PubMed

    Pakhomov, Andrei G; Doyle, Joanne; Stuck, Bruce E; Murphy, Michael R

    2003-04-01

    Effects of short, extremely high power microwave pulses (EHPP) on neuronal network function were explored by electrophysiological techniques in the isolated rat hippocampal slice model. Population spikes (PS) in the CA1 area were evoked by repeated stimulation (1 per 30 s) of the Schaffer collateral pathway. A brief tetanus (2 s at 50 Hz) was used to induce long term potentiation (LTP) of synaptic transmission. In three different series of experiments with a total of 160 brain slices, the EHPP irradiation was performed before, during, or after the tetanus. The EHPP carrier frequency was 9.3 GHz, the pulse width and repetition rate were from 0.5 to 2 micros and from 0.5 to 10 Hz, respectively, and the peak specific absorption rate (SAR) in brain slices reached up to 500 MW/kg. Microwave heating of the preparation ranged from 0.5 degrees C (at 0.3 kW/kg time average SAR) to 6 degrees C (at 3.6 kW/kg). The experiments established that the only effect caused by EHPP exposure within the studied range of parameters was a transient and fully reversible decrease in the PS amplitude. Recovery took no more than a few minutes after the cessation of exposure and return to the initial temperature. This effect's features were characteristic of an ordinary thermal response: it was proportional to the temperature rise but not to any specific parameter of EHPP, and it could also be induced by a continuous wave (CW) irradiation or conventional heating. Irradiation did not affect the ability of neurons to develop LTP in response to tetanus or to retain the potentiated state that was induced before irradiation. No lasting or delayed effects of EHPP were observed. The results are consistent with the thermal mechanism of EHPP action and thus far provided no indication of EHPP-specific effects on neuronal function.

  18. Long-term Cognitive and Functional Effects of Potentially Inappropriate Medications in Older Women

    PubMed Central

    2014-01-01

    Background. The use of potentially inappropriate medications in older adults can lead to known adverse drug events, but long-term effects are less clear. We therefore conducted a prospective cohort study of older women to determine whether PIM use is associated with risk of functional impairment or low cognitive performance. Methods. We followed up 1,429 community-dwelling women (≥75 years) for a period of 5 years at four clinical sites in the United States. The primary predictor at baseline was PIM use based on 2003 Beers Criteria. We also assessed anticholinergic load using the Anticholinergic Cognitive Burden scale. Outcomes included scores on a battery of six cognitive tests at follow-up and having one or more incident impairments in instrumental activities of daily living. Regression models were adjusted for baseline age, race, education, smoking, physical activity, a modified Charlson Comorbidity Index, and cognitive score. Results. The mean ± SD age of women at baseline was 83.2 ± 3.3. In multivariate models, baseline PIM use and higher ACB scores were significantly associated with poorer performance in category fluency (PIM: p = .01; ACB: p = .02) and immediate (PIM: p = .04; ACB: p = .03) and delayed recall (PIM: p = .04). Both PIM use (odds ratio [OR]: 1.36 [1.05–1.75]) and higher ACB scores (OR: 1.11 [1.04–1.19]) were also strongly associated with incident functional impairment. Conclusions. The results provide suggestive evidence that PIM use and increased anticholinergic load may be associated with risk of functional impairment and low cognitive performance. More cautious selection of medications in older adults may reduce these potential risks. PMID:24293516

  19. Antidepressants that inhibit both serotonin and norepinephrine reuptake impair long-term potentiation in hippocampus

    PubMed Central

    Cooke, Jennifer D.; Cavender, Hannah M.; Lima, Hope K.; Grover, Lawrence M.

    2014-01-01

    Rationale Monoamine reuptake inhibitors can stimulate expression of brain-derived neurotrophic factor (BDNF) and alter long-term potentiation (LTP), a widely used model for the synaptic mechanisms that underlie memory formation. BDNF expression is up-regulated during LTP, and BDNF in turn positively modulates LTP. Previously, we found that treatment with venlafaxine, a serotonin and norepinephrine reuptake inhibitor (SNRI), but not citalopram, a selective serotonin reuptake inhibitor (SSRI) reduced LTP in hippocampal area CA1 without changing hippocampal BDNF protein expression. Objectives We tested the hypothesis that combined serotonin and norepinephrine reuptake inhibition is necessary for LTP impairment, and we reexamined the potential role of BNDF by testing for region-specific changes in areas CA1, CA3 and dentate gyrus. We also tested whether early events in the LTP signaling pathway were altered to impair LTP. Methods Animals were treated for 21 days with venlafaxine, imipramine, fluoxetine, or maprotiline. In vitro hippocampal slices were used for electrophysiological measurements. Protein expression was measured by enzyme-linked immunosorbent assay (ELISA) and western blotting. Results LTP was impaired only following treatment with combined serotonin and norepinephrine reuptake inhibitors (venlafaxine, imipramine) but not with selective serotonin (fluoxetine) or norepinephrine (maprotiline) reuptake inhibitors. BDNF protein expression was not altered by venlafaxine or imipramine treatment, nor were postsynaptic depolarization during LTP inducing stimulation or synaptic membrane NMDA receptor subunit expression affected. Conclusions LTP is impaired by chronic treatment with antidepressant that inhibit both serotonin and norepinephrine reuptake; this impairment results from changes that are downstream of postsynaptic depolarization and calcium-influx. PMID:24781518

  20. Transgenerational rescue of a genetic defect in long-term potentiation and memory formation by juvenile enrichment.

    PubMed

    Arai, Junko A; Li, Shaomin; Hartley, Dean M; Feig, Larry A

    2009-02-01

    The idea that qualities acquired from experience can be transmitted to future offspring has long been considered incompatible with current understanding of genetics. However, the recent documentation of non-Mendelian transgenerational inheritance makes such a "Lamarckian"-like phenomenon more plausible. Here, we demonstrate that exposure of 15-d-old mice to 2 weeks of an enriched environment (EE), that includes exposure to novel objects, elevated social interactions and voluntary exercise, enhances long-term potentiation (LTP) not only in these enriched mice but also in their future offspring through early adolescence, even if the offspring never experience EE. In both generations, LTP induction is augmented by a newly appearing cAMP/p38 MAP kinase-dependent signaling cascade. Strikingly, defective LTP and contextual fear conditioning memory normally associated with ras-grf knock-out mice are both masked in the offspring of enriched mutant parents. The transgenerational transmission of this effect occurs from the enriched mother to her offspring during embryogenesis. If a similar phenomenon occurs in humans, the effectiveness of one's memory during adolescence, particularly in those with defective cell signaling mechanisms that control memory, can be influenced by environmental stimulation experienced by one's mother during her youth.

  1. Testing the NMDA, long-term potentiation, and cholinergic hypotheses of spatial learning.

    PubMed

    Cain, D P

    1998-03-01

    The problems and issues associated with the use of pharmacological antagonists in studies on learning and memory are considered in a review of the role of N-methyl-D-aspartate (NMDA) receptors, NMDA receptor-mediated long-term potentiation (LTP), and muscarinic receptors in spatial learning in the water maze. The evidence indicates that neither NMDA nor muscarinic receptors, nor NMDA receptor-mediated LTP, are required for spatial learning, although they might normally contribute to it. Detailed behavioral analyses have indicated that the water maze task is more complex than generally has been appreciated, and has a number of dissociable components. Naive rats trained under NMDA or muscarinic antagonism display sensorimotor disturbances that interfere with their ability to acquire the task. Rats made familiar with the general requirements of the task can learn the location of a hidden platform readily under NMDA or muscarinic antagonism. The ability of a rat to acquire the water maze task depends on its ability to apply instinctive behaviors to performance of the task in an adaptive manner. The instinctive behaviors undergo modification as the rat learns the general strategies required in the task. The evidence suggests that at least some of the plastic changes involved in acquiring the task occur in existing neural circuits situated in widespread areas of the brain, including sensory and motor structures in the cortex and elsewhere, and are therefore difficult to distinguish from existing sensorimotor mechanisms. More generally, the findings indicate the difficulty of inferring the occurrence or nonoccurrence of learning from behavior, and the difficulty of causally linking the action of particular receptor populations with the formation of specific memories.

  2. The potential of Lake Karakul in the eastern Pamirs as a long-term climate archive

    NASA Astrophysics Data System (ADS)

    Mischke, S.; Rajabov, I.; Mustaeva, N.; Zhang, C.; Boomer, I.; Sherlock, S. C.; Myrbo, A.; Noren, A.; Brady, K.; Herzschuh, U.; Schudack, M. E.; Ito, E.

    2008-12-01

    Lake Karakul is a large closed-basin lake in the eastern Pamirs (NE Tajikistan) at an altitude of 3930 m. The lake fills a large basin about 45 km in diameter which may originate from a meteorite impact in the late Neogene. Exposed lake sediments at the northwestern shore 20 m above the lake display a bizarre Yardang relief indicating higher water levels in the past. Eroded remnants of lake, playa and fluvial sediments can be found on the northeastern slopes of the basin 200 m above the lake but their depositional age remains unknown. A field survey of the Lake Karakul region was conducted in July 2008 as a first attempt to evaluate the potential of the lake as a long-term climate archive in Central Asia. Sediment samples from the lake's bottom, water samples from the lake and inflowing streams, aquatic and terrestrial plant samples, and rock samples were collected to enable an interdisciplinary investigation of the lake and its catchment. A 1.04 m sediment core was obtained near the centre of the more shallow and flat eastern sub-basin of the lake at 19 m water depth. Corresponding to the lack of outlet and the resulting high pH (9.1) and electrical conductivity of the lake (10.3 mS/cm), fine aragonite needles constitute most of the sediments. Additionally, ostracod shells, aquatic plant fragments, detrital grains and Radix (Gastropoda) shells were recorded. First results of AMS 14C dating and ostracod analysis will be used to infer the environmental and climatic evolution of Lake Karakul in the Late Holocene.

  3. Effects of exposure to an extremely low frequency electromagnetic field on hippocampal long-term potentiation in rat.

    PubMed

    Komaki, Alireza; Khalili, Afshin; Salehi, Iraj; Shahidi, Siamak; Sarihi, Abdolrahman

    2014-05-20

    Modern lifestyle exposes nearly all humans to electromagnetic fields, particularly to extremely low frequency electromagnetic fields (ELF-EMFs). Prolonged exposure to ELF-EMFs induces persistent changes in neuronal activity. However, the modulation of synaptic efficiency by ELF-EMFs in vivo is still unclear. In the present study, we investigated whether ELF-EMFs can change induction of long-term potentiation (LTP) and paired-pulse ratio (PPR) in the rat hippocampal area. Twenty-nine adult male Wistar rats were divided into 3 groups (ELF-EMF exposed, sham and control groups). The ELF-EMF group was exposed to a magnetic field for 90 consecutive days (2h/day). ELF-EMFs were produced by a circular coil (50Hz, 100 micro Tesla). The sham-exposed controls were placed in an identical chamber with no electromagnetic field. After this period, rats were deeply anesthetized with urethane (2.0mg/kg) and then a bipolar stimulating and recording electrode was implanted into the perforant pathway (PP) and dentate gyrus (DG), respectively. LTP in hippocampal area was induced by high-frequency stimulation (HFS). Prolonged exposure to ELF-EMFs increased LTP induction. There was a significant difference in the slope of EPSP and amplitude of PS between the ELF-EMF group and other groups. In conclusion, our data suggest that exposure to ELF-EMFs produces a marked change in the synaptic plasticity generated in synapses of the PP-DG. No significant difference in PPR of ELF-EMF group before and after HFS suggests a postsynaptic expression site of LTP.

  4. Input- and subunit-specific AMPA receptor trafficking underlying long-term potentiation at hippocampal CA3 synapses.

    PubMed

    Kakegawa, Wataru; Tsuzuki, Keisuke; Yoshida, Yukari; Kameyama, Kimihiko; Ozawa, Seiji

    2004-07-01

    Hippocampal CA3 pyramidal neurons receive synaptic inputs from both mossy fibres (MFs) and associational fibres (AFs). Long-term potentiation (LTP) at these synapses differs in its induction sites and N-methyl-D-aspartate receptor (NMDAR) dependence. Most evidence favours the presynaptic and postsynaptic mechanisms for induction of MF LTP and AF LTP, respectively. This implies that molecular and functional properties differ between MF and AF synapses at both presynaptic and postsynaptic sites. In this study, we focused on the difference in the postsynaptic trafficking of alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors (AMPARs) between these synapses. To trace the subunit-specific trafficking of AMPARs at each synapse, GluR1 and GluR2 subunits were introduced into CA3 pyramidal neurons in hippocampal organotypic cultures using the Sindbis viral expression system. The electrophysiologically-tagged GluR2 AMPARs, produced by the viral-mediated transfer of the unedited form of GluR2 (GluR2Q), were inserted into both MF and AF postsynaptic sites in a neuronal activity-independent manner. Endogenous Ca(2+)-impermeable AMPARs at these synapses were replaced with exogenous Ca(2+)-permeable receptors, and Ca(2+) influx via the newly expressed postsynaptic AMPARs induced NMDAR-independent LTP at AF synapses. In contrast, no GluR1 AMPAR produced by the gene transfer was constitutively incorporated into AF postsynaptic sites, and only a small amount into MF postsynaptic sites. The synaptic trafficking of GluR1 AMPARs was triggered by the activity of Ca(2+)/calmodulin-dependent kinase II or high-frequency stimulation to induce LTP at AF synapses, but not at MF synapses. These results indicate that MF and AF postsynaptic sites possess distinct properties for AMPAR trafficking in CA3 pyramidal neurons.

  5. Opposing Actions of Chronic[Deta][superscript 9] Tetrahydrocannabinol and Cannabinoid Antagonists on Hippocampal Long-Term Potentiation

    ERIC Educational Resources Information Center

    Hoffman, Alexander F.; Oz, Murat; Yang, Ruiqin; Lichtman, Aron H.; Lupica, Carl R.

    2007-01-01

    Memory deficits produced by marijuana arise partly via interaction of the psychoactive component, [Deta][superscript 9]-tetrahydrocannabinol ([Deta][superscript 9]-THC), with cannabinoid receptors in the hippocampus. Although cannabinoids acutely reduce glutamate release and block hippocampal long-term potentiation (LTP), a potential substrate for…

  6. Hormonal and Monoamine Signaling during Reinforcement of Hippocampal Long-Term Potentiation and Memory Retrieval

    ERIC Educational Resources Information Center

    Korz, Volker; Frey, Julietta U.

    2007-01-01

    Recently it was shown that holeboard training can reinforce, i.e., transform early-LTP into late-LTP in the dentate gyrus during the initial formation of a long-term spatial reference memory in rats. The consolidation of LTP as well as of the reference memory was dependent on protein synthesis. We have now investigated the transmitter systems…

  7. Long-Term Exercise Is a Potent Trigger for ΔFosB Induction in the Hippocampus along the dorso–ventral Axis

    PubMed Central

    Nishijima, Takeshi; Kawakami, Masashi; Kita, Ichiro

    2013-01-01

    Physical exercise improves multiple aspects of hippocampal function. In line with the notion that neuronal activity is key to promoting neuronal functions, previous literature has consistently demonstrated that acute bouts of exercise evoke neuronal activation in the hippocampus. Repeated activating stimuli lead to an accumulation of the transcription factor ΔFosB, which mediates long-term neural plasticity. In this study, we tested the hypothesis that long-term voluntary wheel running induces ΔFosB expression in the hippocampus, and examined any potential region-specific effects within the hippocampal subfields along the dorso–ventral axis. Male C57BL/6 mice were housed with or without a running wheel for 4 weeks. Long-term wheel running significantly increased FosB/ΔFosB immunoreactivity in all hippocampal regions measured (i.e., in the DG, CA1, and CA3 subfields of both the dorsal and ventral hippocampus). Results confirmed that wheel running induced region-specific expression of FosB/ΔFosB immunoreactivity in the cortex, suggesting that the uniform increase in FosB/ΔFosB within the hippocampus is not a non-specific consequence of running. Western blot data indicated that the increased hippocampal FosB/ΔFosB immunoreactivity was primarily due to increased ΔFosB. These results suggest that long-term physical exercise is a potent trigger for ΔFosB induction throughout the entire hippocampus, which would explain why exercise can improve both dorsal and ventral hippocampus-dependent functions. Interestingly, we found that FosB/ΔFosB expression in the DG was positively correlated with the number of doublecortin-immunoreactive (i.e., immature) neurons. Although the mechanisms by which ΔFosB mediates exercise-induced neurogenesis are still uncertain, these data imply that exercise-induced neurogenesis is at least activity dependent. Taken together, our current results suggest that ΔFosB is a new molecular target involved in regulating exercise

  8. Free radicals accelerate the decay of long-term potentiation in field CA1 of guinea-pig hippocampus.

    PubMed

    Pellmar, T C; Hollinden, G E; Sarvey, J M

    1991-01-01

    Free radicals have been implicated in a number of pathological conditions. To evaluate the neurophysiological consequences of free radical exposure, slices of hippocampus isolated from guinea-pigs were exposed to hydrogen peroxide which reacts with tissue iron to generate hydroxyl free radicals. Long-term potentiation, a sustained increase in synaptic responses, was elicited in field CA1 by high frequency stimulation of an afferent pathway. We found that 0.002% peroxide did not directly affect the responses evoked by stimulation of the afferent pathway but did prevent maintenance of long-term potentiation. Short-term potentiation and paired-pulse facilitation were not affected by peroxide treatment. Peroxide was less effective if removed following high frequency stimulation and was ineffective if applied only after high frequency stimulation. Input/output analysis showed that the increase in synaptic efficacy was reduced with peroxide treatment. Changes in the enhanced ability of the synaptic potential to generate a spike were less apparent. These data show that the interference of free radicals with long-term potentiation may contribute to pathological deficits. It is possible that intracellular calcium regulation is disrupted by peroxide treatment. A number of second messenger systems involved with long-term potentiation are potential targets for free radical attack.

  9. Alpha5GABAA receptor activity sets the threshold for long-term potentiation and constrains hippocampus-dependent memory.

    PubMed

    Martin, Loren J; Zurek, Agnieszka A; MacDonald, John F; Roder, John C; Jackson, Michael F; Orser, Beverley A

    2010-04-14

    Synaptic plasticity, which is the neuronal substrate for many forms of hippocampus-dependent learning, is attenuated by GABA type A receptor (GABA(A)R)-mediated inhibition. The prevailing notion is that a synaptic or phasic form of GABAergic inhibition regulates synaptic plasticity; however, little is known about the role of GABA(A)R subtypes that generate a tonic or persistent inhibitory conductance. We studied the regulation of synaptic plasticity by alpha5 subunit-containing GABA(A)Rs (alpha5GABA(A)Rs), which generate a tonic inhibitory conductance in CA1 pyramidal neurons using electrophysiological recordings of field and whole-cell potentials in hippocampal slices from both wild-type and null mutant mice for the alpha5 subunit of the GABA(A)R (Gabra5(-/-) mice). In addition, the strength of fear-associated memory was studied. The results showed that alpha5GABA(A)R activity raises the threshold for induction of long-term potentiation in a highly specific band of stimulation frequencies (10-20 Hz) through mechanisms that are predominantly independent of inhibitory synaptic transmission. The deletion or pharmacological inhibition of alpha5GABA(A)Rs caused no change in baseline membrane potential or input resistance but increased depolarization during 10 Hz stimulation. The encoding of hippocampus-dependent memory was regulated by alpha5GABA(A)Rs but only under specific conditions that generate moderate but not robust forms of fear-associated learning. Thus, under specific conditions, alpha5GABA(A)R activity predominates over synaptic inhibition in modifying the strength of both synaptic plasticity in vitro and certain forms of memory in vivo. PMID:20392949

  10. Worldwide impact of aerosol's time scale on the predicted long-term concentrating solar power potential.

    PubMed

    Ruiz-Arias, Jose A; Gueymard, Christian A; Santos-Alamillos, Francisco J; Pozo-Vázquez, David

    2016-08-10

    Concentrating solar technologies, which are fuelled by the direct normal component of solar irradiance (DNI), are among the most promising solar technologies. Currently, the state-of the-art methods for DNI evaluation use datasets of aerosol optical depth (AOD) with only coarse (typically monthly) temporal resolution. Using daily AOD data from both site-specific observations at ground stations as well as gridded model estimates, a methodology is developed to evaluate how the calculated long-term DNI resource is affected by using AOD data averaged over periods from 1 to 30 days. It is demonstrated here that the use of monthly representations of AOD leads to systematic underestimations of the predicted long-term DNI up to 10% in some areas with high solar resource, which may result in detrimental consequences for the bankability of concentrating solar power projects. Recommendations for the use of either daily or monthly AOD data are provided on a geographical basis.

  11. Worldwide impact of aerosol's time scale on the predicted long-term concentrating solar power potential.

    PubMed

    Ruiz-Arias, Jose A; Gueymard, Christian A; Santos-Alamillos, Francisco J; Pozo-Vázquez, David

    2016-01-01

    Concentrating solar technologies, which are fuelled by the direct normal component of solar irradiance (DNI), are among the most promising solar technologies. Currently, the state-of the-art methods for DNI evaluation use datasets of aerosol optical depth (AOD) with only coarse (typically monthly) temporal resolution. Using daily AOD data from both site-specific observations at ground stations as well as gridded model estimates, a methodology is developed to evaluate how the calculated long-term DNI resource is affected by using AOD data averaged over periods from 1 to 30 days. It is demonstrated here that the use of monthly representations of AOD leads to systematic underestimations of the predicted long-term DNI up to 10% in some areas with high solar resource, which may result in detrimental consequences for the bankability of concentrating solar power projects. Recommendations for the use of either daily or monthly AOD data are provided on a geographical basis. PMID:27507711

  12. The APP-Interacting Protein FE65 is Required for Hippocampus-Dependent Learning and Long-Term Potentiation

    ERIC Educational Resources Information Center

    Wang, Yan; Zhang, Ming; Moon, Changjong; Hu, Qubai; Wang, Baiping; Martin, George; Sun, Zhongsheng; Wang, Hongbing

    2009-01-01

    FE65 is expressed predominantly in the brain and interacts with the C-terminal domain of [beta]-amyloid precursor protein (APP). We examined hippocampus-dependent memory and in vivo long-term potentiation (LTP) at the CA1 synapses with isoform-specific FE65 knockout (p97FE65[superscript -/-]) mice. When examined using the Morris water maze,…

  13. Corticosterone Time-Dependently Modulates [beta]-Adrenergic Effects on Long-Term Potentiation in the Hippocampal Dentate Gyrus

    ERIC Educational Resources Information Center

    Pu, Zhenwei; Krugers, Harm J.; Joels, Marian

    2007-01-01

    Previous experiments in the hippocampal CA1 area have shown that corticosterone can facilitate long-term potentiation (LTP) in a rapid non-genomic fashion, while the same hormone suppresses LTP that is induced several hours after hormone application. Here, we elaborated on this finding by examining whether corticosterone exerts opposite effects on…

  14. Long-term concentrations of airborne cadmium in metropolitan cities in Korea and potential health risks

    NASA Astrophysics Data System (ADS)

    Mutlu, Atilla; Lee, Byeong-Kyu; Park, Gee-Hyeong; Yu, Bong-Gwan; Lee, Chi-Hyeon

    2012-02-01

    The long-term concentrations of cadmium (Cd) in total suspended particulate (TSP) were calculated from data obtained from 30 ambient air-monitoring stations (AAMSs) located in seven metropolitan cities throughout Korea. The annual mean levels of Cd in TSP in port cities, industrial cities, and an inland city showed a decreasing trend over the 7-year study period. The overall highest average concentration was observed in Incheon with an annual mean of 3.92 ± 1.62 ng m -3, followed by Ulsan and Busan. The long-term Cd mean levels from international port and/or industrial cities (Incheon, Ulsan, Busan) were much higher than those from inland cities (Seoul, Daegu, Daejeon, and Gwangju). Temporal analysis indicated that there were no significant differences among Cd levels in different seasons. However, in Incheon, the seasonal average concentrations of Cd in spring, winter, and fall were 5.20 (±3.27) ng m -3, 4.01 (±0.93) ng m -3, and 3.5 (±0.77) ng m -3, respectively, which were significantly higher levels than those measured in the other cities for the corresponding seasons. These high concentrations in Incheon are likely due to the combined effects of local industries, traffic, ship emissions, and long-range transported PM from the northeastern industrial regions of China. The long-term summer average concentration in Ulsan, the largest industrial city, was 4.58 ± 1.15 ng m -3, which was significantly higher than the other seasonal values and also the summer averages of the other cities. This can be explained by downwind location effects of prevailing winds that pass through the industrial and port sectors of Ulsan. Excess cancer risk (ECR) estimates indicated that the carcinogenic risk due to inhaled Cd is 7, 6, and 4 persons per million of population in Incheon, Ulsan, and Busan, respectively.

  15. Long-term potentiation of inhibitory synaptic transmission onto cerebellar Purkinje neurons contributes to adaptation of vestibulo-ocular reflex.

    PubMed

    Tanaka, Shinsuke; Kawaguchi, Shin-Ya; Shioi, Go; Hirano, Tomoo

    2013-10-23

    Synaptic plasticity in the cerebellum is thought to contribute to motor learning. In particular, long-term depression (LTD) at parallel fiber (PF) to Purkinje neuron (PN) excitatory synapses has attracted much attention of neuroscientists as a primary cellular mechanism for motor learning. In contrast, roles of plasticity at cerebellar inhibitory synapses in vivo remain unknown. Here, we have investigated the roles of long-lasting enhancement of transmission at GABAergic synapses on a PN that is known as rebound potentiation (RP). Previous studies demonstrated that binding of GABAA receptor with GABAA receptor-associated protein (GABARAP) is required for RP, and that a peptide that blocks this binding suppresses RP induction. To address the functional roles of RP, we generated transgenic mice that express this peptide fused to a fluorescent protein selectively in PNs using the PN-specific L7 promoter. These mice failed to show RP, although they showed no changes in the basal amplitude or frequency of miniature IPSCs. The transgenic mice also showed no abnormality in gross cerebellar morphology, LTD, or other excitatory synaptic properties, or intrinsic excitability of PNs. Next, we attempted to evaluate their motor control and learning ability by examining reflex eye movements. The basal dynamic properties of the vestibulo-ocular reflex and optokinetic response, and adaptation of the latter, were normal in the transgenic mice. In contrast, the transgenic mice showed defects in the adaptation of vestibulo-ocular reflex, a model paradigm of cerebellum-dependent motor learning. These results together suggest that RP contributes to a certain type of motor learning.

  16. Effects of repeated prenatal glucocorticoid exposure on long-term potentiation in the juvenile guinea-pig hippocampus.

    PubMed

    Setiawan, Elaine; Jackson, Michael F; MacDonald, John F; Matthews, Stephen G

    2007-06-15

    Synthetic glucocorticoids (sGCs) are routinely used to treat women at risk of preterm labour to promote fetal lung maturation. There is now strong evidence that exposure to excess glucocorticoid during periods of rapid brain development has permanent consequences for endocrine function and behaviour in the offspring. Prenatal exposure to sGC alters the expression of N-methyl-D-aspartate receptor (NMDA-R) subunits in the fetal and neonatal hippocampus. Given the integral role of the NMDA-R in synaptic plasticity, we hypothesized that prenatal sGC exposure will have effects on hippocampal long-term potentiation (LTP) after birth. Further, this may occur in either the presence or absence of elevated cortisol concentrations, in vitro. Pregnant guinea-pigs were injected with betamethasone (Beta, 1 mg kg(-1)) or vehicle on gestational days (gd) 40, 41, 50, 51, 60 and 61 (term approximately 70 days), a regimen comparable to that given to pregnant women. On postnatal day 21, LTP was examined at Schaffer collateral synapses in the CA1 region of hippocampal slices prepared from juvenile animals exposed to betamethasone or vehicle, in utero. Subsequently, the acute glucocorticoid receptor (GR)- and mineralocorticoid receptor (MR)-dependent effects of cortisol (0.1-10 microM; bath applied 30 min before LTP induction) were examined. There was no effect of prenatal sGC treatment on LTP under basal conditions. The application of 10 microM cortisol depressed excitatory synaptic transmission in all treatment groups regardless of sex. Similarly, LTP was depressed by 10 microM cortisol in all groups, with the exception of Beta-exposed females, in which LTP was unaltered. Hippocampal MR and GR protein levels were increased in Beta-exposed females, but not in any other prenatal treatment group. This study reveals sex-specific effects of prenatal exposure to sGC on LTP in the presence of elevated cortisol, a situation that would occur in vivo during stress.

  17. Oxaloacetate restores the long-term potentiation impaired in rat hippocampus CA1 region by 2-vessel occlusion.

    PubMed

    Marosi, Máté; Fuzik, János; Nagy, Dávid; Rákos, Gabriella; Kis, Zsolt; Vécsei, László; Toldi, József; Ruban-Matuzani, Angela; Teichberg, Vivian I; Farkas, Tamás

    2009-02-14

    Various acute brain pathological conditions are characterized by the presence of elevated glutamate concentrations in the brain interstitial fluids. It has been established that a decrease in the blood glutamate level enhances the brain-to-blood efflux of glutamate, removal of which from the brain may prevent glutamate excitotoxicity and its contribution to the long-lasting neurological deficits seen in stroke. A decrease in blood glutamate level can be achieved by exploiting the glutamate-scavenging properties of the blood-resident enzyme glutamate-oxaloacetate transaminase, which transforms glutamate into 2-ketoglutarate in the presence of the glutamate co-substrate oxaloacetate. The present study had the aim of an evaluation of the effects of the blood glutamate scavenger oxaloacetate on the impaired long-term potentiation (LTP) induced in the 2-vessel occlusion ischaemic model in rat. Transient (30-min) incomplete forebrain ischaemia was produced 72 h before LTP induction. Although the short transient brain hypoperfusion did not induce histologically identifiable injuries in the CA1 region (Fluoro-Jade B, S-100 and cresyl violet), it resulted in an impaired LTP function in the hippocampal CA1 region without damaging the basal synaptic transmission between the Schaffer collaterals and the pyramidal neurons. This impairment could be fended off in a dose-dependent manner by the intravenous administration of oxaloacetate in saline (at doses between 1.5 mmol and 0.1 mumol) immediately after the transient hypoperfusion. Our results suggest that oxaloacetate-mediated blood and brain glutamate scavenging contributes to the restoration of the LTP after its impairment by brain ischaemia.

  18. Pairing-specific long-term depression of Purkinje cell excitatory postsynaptic potentials results from a classical conditioning procedure in the rabbit cerebellar slice.

    PubMed

    Schreurs, B G; Oh, M M; Alkon, D L

    1996-03-01

    blocked PSD and that, in turn, PSD involved protein kinases. 6. The means of induction and the specificity of those means suggest that the phenomenology of PSD is fundamentally different from that of long-term depression. PSD only occurs with pairings of trains of parallel fiber and climbing fiber stimulation; it occurs without the need for bicuculline; and it can overcome the blocking effects of aniracetam. 7. Nevertheless, the involvement of protein kinases and the potential role of calcium suggest that the mechanisms involved in the induction of PSD and long-term depression have a number of features in common. 8. Because of the pairing-specific nature of the long-term synaptic depression observed in these experiments, PSD provides a mechanism that may contribute to the role of the cerebellar cortex in classical conditioning.

  19. Effects of antipsychotic D2 antagonists on long-term potentiation in animals and implications for human studies.

    PubMed

    Price, Rae; Salavati, Bahar; Graff-Guerrero, Ariel; Blumberger, Daniel M; Mulsant, Benoit H; Daskalakis, Zafiris J; Rajji, Tarek K

    2014-10-01

    In people with schizophrenia, cognitive abilities - including memory - are strongly associated with functional outcome. Long-term potentiation (LTP) is a form of neuroplasticity that is believed to be the physiological basis for memory. It has been postulated that antipsychotic medication can impair long-term potentiation and cognition by altering dopaminergic transmission. Thus, a systematic review was performed in order to assess the relationship between antipsychotics and D2 antagonists on long-term potentiation. The majority of studies on LTP and antipsychotics have found that acute administration of antipsychotics was associated with impairments in LTP in wild-type animals. In contrast, chronic administration and acute antipsychotics in animal models of schizophrenia were not. Typical and atypical antipsychotics and other D2 antagonists behaved similarly, with the exception of clozapine and olanzapine. Clozapine caused potentiation independent of tetanization, while olanzapine facilitated tetanus-induced potentiation. These studies are limited in their ability to model the effects of antipsychotics in patients with schizophrenia as they were largely performed in wild-type animals as opposed to humans with schizophrenia, and assessed after acute rather than chronic treatment. Further studies using patients with schizophrenia receiving chronic antipsychotic treatment are needed to better understand the effects of these medications in this population.

  20. The postsynaptic induction of nonassociative long-term depression of excitatory synaptic transmission in rat hippocampal slices.

    PubMed

    Christofi, G; Nowicky, A V; Bolsover, S R; Bindman, L J

    1993-01-01

    1. Long-term depression (LTD) is an activity-dependent reduction in the strength of synaptic transmission that can persist for hours. It is a neural model for processes underlying learning and memory, such as extinction and forgetting. LTD of excitatory postsynaptic potentials (EPSPs) in cells of the CA1 region of hippocampal slices can be induced in an anti-Hebbian paradigm, i.e., by conditioning stimuli that activate the postsynaptic neuron in the absence of evoked synaptic transmission in the test pathway. Past work showed that LTD was not produced consistently in a pharmacologically untreated slice, but it could be induced more reliably when the conditioning stimuli were applied during block of evoked transmitter release. We have now defined further the conditions in which LTD can be obtained using postsynaptic conditioning by investigating 1) whether intracellular conditioning is effective, 2) the requirement for extracellular Ca2+, and 3) the consequences of selective block of glutamate ionotropic receptor subtypes during the conditioning procedure. 2. Intracellular recordings were made from CA1 pyramidal neurons. Test shocks were applied to the stratum radiatum except during conditioning, and the depolarizing slopes and amplitudes of evoked EPSPs were measured. The conditioning procedure activated the postsynaptic neuron either antidromically (via trains of shocks at 100 Hz applied to the axons in the alveus) or intracellularly (via depolarizing pulses of 1.5-3.5 nA). During conditioning, postsynaptic potentials (PSPs) evoked by the conditioning stimuli either were transiently blocked by bathing slices for 5 min in artificial cerebrospinal fluid (CSF) containing a high [Mg2+] or were reduced by glutamate antagonists. 3. When slices were bathed in CSF containing 25 mM Mg2+ and 2 mM Ca2+, evoked PSPs were transiently abolished; conditioning, either by antidromic or intracellular stimulation, always evoked a significant LTD. During the LTD produced by

  1. Voluntary exercise rescues deficits in spatial memory and long-term potentiation in prenatal ethanol-exposed male rats.

    PubMed

    Christie, Brian R; Swann, Sarah E; Fox, Christopher J; Froc, David; Lieblich, Stephanie E; Redila, Van; Webber, Alina

    2005-03-01

    Prenatal ethanol exposure can lead to long-lasting impairments in the ability to process spatial information in rats, as well as produce long-lasting deficits in the ability of animals to exhibit long-term potentiation, a biological model of learning and memory processing. Conversely, we have recently shown that both spatial memory and long-term potentiation can be enhanced in animals that are given access to a running wheel in their home cage. In the present study, Sprague-Dawley rat dams were given one of three diets throughout gestation: (i) a liquid diet containing ethanol (35.5% ethanol-derived calories); (ii) a liquid diet, isocaloric to the ethanol diet, but with maltose-dextrin substituting for the ethanol derived calories and (iii) an ad libitum diet of standard rat chow. At weaning (28 days) animals were housed individually in either a standard rat cage, or a cage that contained a running wheel. Adult offspring were tested on a two trial version of the Morris water maze beginning at postnatal day 60, for five consecutive days. Following this, the capacity of the perforant path to dentate gyrus pathway to sustain long-term potentiation was examined in these animals using theta-patterned conditioning stimuli. Our results demonstrate that prenatal ethanol exposure can produce pronounced deficits in both spatial memory and long-term potentiation, but that allowing animal's access to voluntary exercise can attenuate these deficits to the point that those exposed to ethanol prenatally can no longer be differentiated from control animals. These findings indicate that voluntary exercise may have therapeutic benefits for individuals that have undergone prenatal ethanol exposure.

  2. Peat as a potential analogue for the long-term evolution in landfills

    NASA Astrophysics Data System (ADS)

    Bozkurt, S.; Lucisano, M.; Moreno, L.; Neretnieks, I.

    2001-03-01

    A survey of the existing studies on peat and its decomposition processes is presented with the aim to characterise the long-term behaviour of peat accumulating systems. The chemical and physical characteristics of peat together with its accumulation and decay processes have been analysed. Peat is an acidic mixture of dead and decomposed, mainly vegetable, matter formed in boggy areas; it is the youngest and least altered component of the combustible rocks and is characterised by the lowest content of fixed carbon and the highest content of volatile constituents. Peat is formed by degeneration processes under exclusion of atmospheric oxygen by the action of water; the speed of formation depends upon the climatic and environmental conditions. In most peatlands two layers can be characterised: the aerobic acrotelm and the anaerobic catotelm, their relative importance being controlled mainly by the position of the water table. In the acrotelm the aerobic processes are responsible for the loss of up to 90% of the original mass. Degeneration in the acidic and anaerobic catotelm is still imperfectly characterised even though the catotelm is the real site of peat accumulation. Most of the recent literature considers peat as composed of easily degradable compounds, e.g. polysaccharides, and recalcitrant matter (lignin and complex aromatics). The long-term destiny of peat has not been sufficiently characterised: although in a large majority of cases it seems probable that peat decomposes completely (even though slowly) provided that it is given a sufficiently long residence time in the catotelm, some cases can still be interpreted as examples of simple accumulation. The rates of influx of oxygen and hence the degradation of organic matter into both saturated and partially saturated peat have been estimated. The depletion rate is about 4500 g m -2 year -1 for partially saturated peat. The average depletion rate of the peat for this case will then be such that it will take on

  3. Long-term scar quality in burns with three distinct healing potentials: A multicenter prospective cohort study.

    PubMed

    Goei, Harold; van der Vlies, Cornelis H; Hop, M Jenda; Tuinebreijer, Wim E; Nieuwenhuis, Marianne K; Middelkoop, Esther; van Baar, Margriet E

    2016-07-01

    The laser Doppler imager is used in cases of indeterminate burn depth to accurately predict wound healing time at an early stage. The laser Doppler imager classifies burns into three estimated healing potentials as follows: high, <14 days; intermediate, 14-21 days; and low, >21 days. At this time, the relationship between these healing potentials and long-term scar quality is unknown. The objective of this study was to determine the long-term scar quality of burns with three distinct healing potentials. The secondary objectives were to compare treatment strategies in intermediate wounds, to study the effect of the timing of surgery on low healing potential wounds and to identify predictors of reduced scar quality. Hence, in a prospective cohort study, scar quality was determined in patients whose burns were assessed with laser Doppler imaging. Scar Quality was assessed with objective and subjective measurement tools, including overall scar quality (Patient and Observer Scar Assessment Scale) as a primary outcome and color and elasticity parameters. A total of 141 patients (>19 months postburn) with 216 scars were included. Wounds with high and intermediate healing potential did not significantly differ regarding scar quality. Wounds with a low healing potential had a significantly lower scar quality. Analysis of 76 surgically treated low healing potential wounds showed no significant differences in the primary outcome regarding the timing of surgery (≤14 days vs. >14). Predictors of reduced long-term scar quality were darker skin type and multiple surgeries. In conclusion, scar quality was strongly related to the healing potential category. Scar quality was very similar in high and intermediate healing potential wounds. No positive effects were found on scar quality or on healing time in surgically treated wounds with intermediate healing potential, advocating a conservative approach. Further studies should focus on the optimal timing of surgery in low healing

  4. Long-term characterization of residential runoff and assessing potential surrogates of fecal indicator organisms.

    PubMed

    Reano, Dane C; Haver, Darren L; Oki, Lorence R; Yates, Marylynn V

    2015-05-01

    Investigations into the microbiological impacts of urban runoff on receiving water bodies, especially during storm conditions, have yielded general paradigms that influence runoff abatement and control management strategies. To determine whether these trends are present in other runoff sources, the physical, chemical, and microbiological components of residential runoff from eight neighborhoods in Northern and Southern California were characterized over the course of five years. Sampling occurred regularly and during storm events, resulting in 833 data sets. Analysis of runoff data assisted in characterizing residential runoff, elucidating differences between dry and storm conditions, and identifying surrogates capable of assessing microbiological quality. Results indicate that although microbial loading increases during storm events similar to urban runoff, annual microbial loading in these study sites principally occurs during dry conditions (24% storm, 76% dry). Generated artificial neural network and multiple linear regression models assessed surrogate performance by accurately predicting Escherichia coli concentrations from validation data sets (R(2) = 0.74 and 0.77, respectively), but required input from other fecal indicator organism (FIO) variables to maintain performance (R(2) = 0.27 and 0.18, respectively, without FIO). This long-term analysis of residential runoff highlights characteristics distinct from urban runoff and establishes necessary variables for determining microbiological quality, thus better informing future management strategies.

  5. Glutamate uptake determines pathway specificity of long-term potentiation in the neural circuitry of fear conditioning.

    PubMed

    Tsvetkov, Evgeny; Shin, Ryong Moon; Bolshakov, Vadim Y

    2004-01-01

    Long-term synaptic modifications in afferent inputs to the amygdala underlie fear conditioning in animals. Fear conditioning to a single sensory modality does not generalize to other cues, implying that synaptic modifications in fear conditioning pathways are input specific. The mechanisms of pathway specificity of long-term potentiation (LTP) are poorly understood. Here we show that inhibition of glutamate transporters leads to the loss of input specificity of LTP in the amygdala slices, as assessed by monitoring synaptic responses at two independent inputs converging on a single postsynaptic neuron. Diffusion of glutamate ("spillover") from stimulated synapses, paired with postsynaptic depolarization, is sufficient to induce LTP in the heterosynaptic pathway, whereas an enzymatic glutamate scavenger abolishes this effect. These results establish active glutamate uptake as a crucial mechanism maintaining the pathway specificity of LTP in the neural circuitry of fear conditioning.

  6. Targeting of ribosomal protein S6 to dendritic spines by in vivo high frequency stimulation to induce long-term potentiation in the dentate gyrus

    PubMed Central

    Nihonmatsu, Itsuko; Ohkawa, Noriaki; Saitoh, Yoshito; Inokuchi, Kaoru

    2015-01-01

    ABSTRACT Late phase long-term potentiation (L-LTP) in the hippocampus is believed to be the cellular basis of long-term memory. Protein synthesis is required for persistent forms of synaptic plasticity, including L-LTP. Neural activity is thought to enhance local protein synthesis in dendrites, and one of the mechanisms required to induce or maintain the long-lasting synaptic plasticity is protein translation in the dendrites. One regulator of translational processes is ribosomal protein S6 (rpS6), a component of the small 40S ribosomal subunit. Although polyribosomes containing rpS6 are observed in dendritic spines, it remains unclear whether L-LTP induction triggers selective targeting of the translational machinery to activated synapses in vivo. Therefore, we investigated synaptic targeting of the translational machinery by observing rpS6 immunoreactivity during high frequency stimulation (HFS) for L-LTP induction in vivo. Immunoelectron microscopic analysis revealed a selective but transient increase in rpS6 immunoreactivity occurring as early as 15 min after the onset of HFS in dendritic spine heads at synaptic sites receiving HFS. Concurrently, levels of the rpS6 protein rapidly declined in somata of granule cells, as determined using immunofluorescence microscopy. These results suggest that the translational machinery is rapidly targeted to activated spines and that this targeting mechanism may contribute to the establishment of L-LTP. PMID:26432888

  7. Potential Role of Plasma Myeloperoxidase Level in Predicting Long-Term Outcome of Acute Myocardial Infarction

    PubMed Central

    Kaya, Mehmet Gungor; Yalcin, Ridvan; Okyay, Kaan; Poyraz, Fatih; Bayraktar, Nilufer; Pasaoglu, Hatice; Boyaci, Bulent; Cengel, Atiye

    2012-01-01

    We investigated the prognostic importance of plasma myeloperoxidase levels in patients with ST-elevation myocardial infarction (STEMI) at long-term follow-up, and we analyzed the correlations between plasma myeloperoxidase levels and other biochemical values. We evaluated 73 consecutive patients (56 men; mean age, 56 ±11 yr) diagnosed with acute STEMI and 46 age- and sex-matched healthy control participants. Patients were divided into 2 groups according to the median myeloperoxidase level (Group 1: plasma myeloperoxidase ≤68 ng/mL; and Group 2: plasma myeloperoxidase >68 ng/mL). Patients were monitored for the occurrence of major adverse cardiovascular events (MACE), which were defined as cardiac death; reinfarction; new hospital admission for angina; heart failure; and revascularization procedures. The mean follow-up period was 25 ± 16 months. Plasma myeloperoxidase levels were higher in STEMI patients than in control participants (82 ± 34 vs 20 ±12 ng/mL; P=0.001). Composite MACE occurred in 12 patients with high myeloperoxidase levels (33%) and in 4 patients with low myeloperoxidase levels (11%) (P=0.02). The incidences of nonfatal recurrent myocardial infarction and verified cardiac death were higher in the high-mye-loperoxidase group. In multivariate analysis, high plasma myeloperoxidase levels were independent predictors of MACE (odds ratio = 3.843; <95% confidence interval, 1.625–6.563; P=0.003). High plasma myeloperoxidase levels identify patients with a worse prognosis after acute STEMI at 2-year follow-up. Evaluation of plasma myeloperoxidase levels might be useful in determining patients at high risk of death and MACE who can benefit from further aggressive treatment and closer follow-up. PMID:22949765

  8. Long-term potentiation increases tyrosine phosphorylation of the N-methyl-D-aspartate receptor subunit 2B in rat dentate gyrus in vivo.

    PubMed Central

    Rosenblum, K; Dudai, Y; Richter-Levin, G

    1996-01-01

    Long-term potentiation (LTP) is a form of synaptic memory that may subserve developmental and behavioral plasticity. An intensively investigated form of LTP is dependent upon N-methyl-D-aspartate (NMDA) receptors and can be elicited in the dentate gyrus and hippocampal CA1. Induction of this type of LTP is triggered by influx of Ca2+ through activated NMDA receptors, but the downstream mechanisms of induction, and even more so of LTP maintenance, remain controversial. It has been reported that the function of NMDA receptor channel can be regulated by protein tyrosine kinases and protein phosphatases and that inhibition of protein tyrosine kinases impairs induction of LTP. Herein we report that LTP in the dentate gyrus is specifically correlated with tyrosine phosphorylation of the NMDA receptor subunit 2B in an NMDA receptor-dependent manner. The effect is observed with a delay of several minutes after LTP induction and persists in vivo for several hours. The potential relevance of this post-translational modification to mechanisms of LTP and circuit plasticity is discussed. Images Fig. 1 Fig. 2 PMID:8816822

  9. Activation of presynaptic and postsynaptic ryanodine-sensitive calcium stores is required for the induction of long-term depression at GABAergic synapses in the neonatal rat hippocampus.

    PubMed

    Caillard, O; Ben-Ari, Y; Gaïarsa, J L

    2000-09-01

    The role of internal calcium stores in the induction of long-term depression at GABAergic synapses was investigated in the neonatal rat hippocampus. Whole-cell recordings of CA3 pyramidal neurons were performed on hippocampal slices from neonatal (2-4 d old) rats. In control conditions, tetanic stimulation (TS) evoked an NMDA-dependent long-term depression of GABA(A) receptor-mediated postsynaptic responses (LTD(GABA-A)). LTD(GABA-A) was prevented when the cells were loaded with ruthenium red, a blocker of Ca2+-induced Ca2+ release (CICR) stores, whereas loading the cells with heparin, a blocker of IP3-induced Ca2+ release stores, had no effect. The effects of ryanodine, another compound that interferes with CICR stores, were also investigated. Intracellular injection of ryanodine prevented the induction of LTD(GABA-A) only when the TS was preceded by depolarizing pulses that increase intracellular Ca2+ concentration. When applied in the bath, ryanodine prevented the induction of LTD(GABA-A). Altogether, these results suggest that ryanodine acts as a Ca2+-dependent blocker of CICR stores and that the induction of LTD(GABA-A) required the activation of both presynaptic and postsynaptic CICR stores.

  10. Thyroid-stimulating hormone (TSH)-directed induction of the CREM gene in the thyroid gland participates in the long-term desensitization of the TSH receptor.

    PubMed Central

    Lalli, E; Sassone-Corsi, P

    1995-01-01

    Thyroid gland function is regulated by the hypothalamic-pituitary axis via the secretion of TSH, according to environmental, developmental, and circadian stimuli. TSH modulates both the secretion of thyroid hormone and gland trophism through interaction with a specific guanine nucleotide-binding protein-coupled receptor (TSH receptor; TSH-R), which elicits the activation of the cAMP-dependent signaling pathway. After TSH stimulation, the levels of TSH-R RNA are known to decrease dramatically within a few hours. This phenomenon ultimately leads to homologous long-term desensitization of the TSH-R. Here we show that TSH drives the induction of the inducible cAMP early repressor (ICER) isoform of the cAMP response element (CRE) modulator gene both in rat thyroid gland and in the differentiated thyroid cell line FRTL-5. The kinetics of ICER protein induction mirrors the down-regulation of TSH-R mRNA. ICER binds to a CRE-like sequence in the TSH-R promoter and represses its expression. Thus, ICER induction by TSH in the thyroid gland represents a paradigm of the molecular mechanism by which pituitary hormones elicit homologous long-term desensitization. Images Fig. 1 Fig. 2 Fig. 3 PMID:7568187

  11. Endocrine therapy of transsexualism and potential complications of long-term treatment.

    PubMed

    Futterweit, W

    1998-04-01

    Physiological principles of the interrelationship of sex hormones and their regulation are the foundation of understanding appropriate treatment of the transsexual patient. While both genetic males and females have estrogens and androgens, the quantitative sex hormone production is genetically predetermined by sex hormone production both in the gonads and via peripheral conversion of hormone precursors to sex steroids. Sex hormones exert a negative feedback on the hypothalamus and pituitary gland whereby gonadotropin-releasing hormone (GnRH), pituitary luteinizing hormone (LH), and follicle-stimulating hormone (FSH) are regulated or suppressed by the endogenous levels of these hormones. Sex hormonal therapy induces attenuated GnRH stimulation of LH and FSH causing a reduction of serum sex hormone levels. It is clear that estrogen as well as androgen therapy have a dual role: (i) induction of feminization or virilization and (ii) suppression of the hypothalamic-pituitary-gonadal axis leading to a reduction of endogenous estradiol or testosterone secretion. Cross-sex hormonal treatment may have substantial medical side effects. The smallest dosage of hormonal therapy compatible with the above clinical aims should be used.

  12. Hyaluronan preserves the proliferation and differentiation potentials of long-term cultured murine adipose-derived stromal cells

    SciTech Connect

    Chen, P.-Y.; Huang, Lynn L.H. . E-mail: lynn@mail.ncku.edu.tw; Hsieh, H.-J. . E-mail: hjhsieh@ntu.edu.tw

    2007-08-17

    For long-term culture, murine adipose-derived stromal cells (mADSCs) at latter passages demonstrated a marked decline in proliferative activity, exhibited senescent morphology and reduced differentiation potentials, particularly osteogenesis. To extend the lifespan of mADSCs, two culture conditions containing hyaluronan (HA) was compared in our study, one as a culture medium supplement (SHA), and the other where HA was pre-coated on culture surface (CHA). mADSCs cultivated with SHA exhibited a prolonged lifespan, reduced cellular senescence, and enhanced osteogenic potential compared to regular culture condition (control). Upon CHA treatment, mADSCs tended to form cell aggregates with gradual growth profiles, while their differentiation activities remained similar to SHA groups. After transferring mADSCs from CHA to control surface, they were shown to have an extended lifespan and an increase of osteogenic potential. Our results suggested that HA can be useful for preserving the proliferation and differentiation potentials of long-term cultured mADSCs.

  13. Potential for long-term LNG supplies to the United States

    SciTech Connect

    Lihn, M.L.

    1992-02-01

    Topics discussed here include: (1) terminal capacity; (2) potential sources for US LNG (liquefied natural gas) imports; (3) LNG liquefaction and transportation capacity; (4) historical US LNG imports; (5) LNG supply costs; (6)delivered cost of future LNG imports.

  14. Assessment of the potential for long-term toxicological effects of the Exxon Valdez oil spill on birds and mammals

    SciTech Connect

    Hartung, R.

    1995-12-31

    This paper assesses the potential for direct long-term toxicological effects of exposures to oils in birds and mammals by tracing exposures and effects form the initial cute phases through the sub-chronic to the eventual long-term exposures. The immediate effects of oil spills are physical, the oil acting on the plumage of birds or the fur of mammals. This causes a loss of entrained air and a concomitant reduction in buoyancy and thermal insulation. Animals that escape the immediate impacts may be isolated from their food supply and often ingest large amounts of oil while attempting to clean themselves. At the comparatively high dose levels involved, these exposures can result in toxicologically significant responses in many organ systems. In the course of an oil pollution incident, the amounts of biologically available oils decrease steadily, and simultaneously the composition of the oils shifts towards those components that have low volatility, and that resist photo- and bio-degradation. As this occurs, the primary pathways of exposure change from direct intakes to indirect routes involving the food supply. Although laboratory studies often report finding some adverse effects, the dose rates employed in many of these studies are extremely high when compared with those that are potentially available to animals in the wild, and very few actually use weathered oils. An assessment of the toxicological literature and of the available empirical data on the Exxon Valdez oil spill leads to the conclusion that long-term sub-lethal toxic effects of crude oils on wildlife in such marine spills appear to be very unlikely. 111 refs., 4 figs., 1 tab.

  15. Potentially mineralizable nitrogen as a soil health indicator in a Long-Term Agroecosystem Research site

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Potentially mineralizable nitrogen (PMN) has demonstrated utility as a valuable soil health indicator. However, the relationship between the total PMN pool and nitrogen mineralization rates has not been well described. A better understanding of PMN dynamics in agroecosystems is essential for optimiz...

  16. Long Term Corrosion Potential and Corrosion Rate of Creviced Alloy 22 in Chloride Plus Nitrate Brines

    SciTech Connect

    Evans, K J; Stuart, M L; Etien, R A; Hust, G A; Estill, J C; Rebak, R B

    2005-11-05

    Alloy 22 is a nickel base alloy highly resistant to all forms of corrosion. In conditions where tight crevices exist in hot chloride containing solutions and at anodic potentials, Alloy 22 may suffer crevice corrosion, a form of localized attack. The occurrence (or not) of crevice corrosion in a given environment (e.g. salt concentration and temperature), is governed by the values of the critical potential (E{sub crit}) for crevice corrosion and the corrosion potential (E{sub corr}) that the alloy may establish in the studied environment. If E{sub corr} is equal or higher than E{sub crit}, crevice corrosion may be expected. In addition, it is generally accepted that as Alloy 22 becomes passive in a certain environment, its E{sub corr} increases and its corrosion rate (CR) decreases. This paper discusses the evolution of E{sub corr} and corrosion rate (CR) of creviced Alloy 22 specimens in six different mixtures of sodium chloride (NaCl) and potassium nitrate (KNO{sub 3}) at 100 C. The effect of immersion time on the value of E{sub crit} was also determined. Two types of specimens were used, polished as-welded (ASW) and as-welded plus solution heat-treated (ASW+SHT). The latter contained the black annealing oxide film on the surface. Results show that, as the immersion time increases, E{sub corr} increased and the CR decreased. Even for highly concentrated brine solutions at 100 C the CR was < 30 nm/year after more than 250 days immersion. Some of the exposed specimens (mainly the SHT specimens) suffered crevice corrosion at the open circuit potential in the naturally aerated brines. Immersion times of over 250 days did not reduce the resistance of Alloy 22 to localized corrosion.

  17. The Long-Term Market Potential of Concentrating Solar Power (CSP) Systems

    SciTech Connect

    Smith, Steven J.

    2012-10-30

    This chapter will examine the conditions under which thermal CSP systems might play a large role in the global energy system. CSP technologies, such as troughs or power towers, have a large advantage over other solar technologies in that they offer the potential for firm power delivery, mitigating intermittency issues. These systems require relatively cloud-free conditions to operate, which limits their geographic applicability.

  18. The carcinogenic potential of twelve refined mineral oils following long-term topical application.

    PubMed Central

    Doak, S. M.; Brown, V. K.; Hunt, P. F.; Smith, J. D.; Roe, F. J.

    1983-01-01

    Twelve mineral oils, originating from naphthenic and paraffinic stocks and variously refined, were evaluated for their potential to induce cutaneous neoplasia in female CF1 mice. The oils were applied to the shorn dorsal skin for up to 78 weeks, using several different treatment regimes. The sole acid/earth refined naphthenic spindle oil was a moderately potent cutaneous carcinogen. By comparison, the 11 oils, processed by other refining routes, were less carcinogenic or non-carcinogenic to murine skin. Two of the 11 oils were weak cutaneous carcinogens viz, a naphthenic spindle oil refined only by mild hydrotreatment and a paraffinic spindle oil refined by mild solvent extraction and 'Ferrofining'. All 9 remaining oils had been solvent-extracted as part of the secondary refining process; none induced malignant tumours, although solitary benign tumours of the treated site were recorded after exposure to 3 oils. The cutaneous carcinogenic potential of the test oils did not correlate well with their potential to induce epidermal hyperplasia at the treated site. Consequently, hyperplasia caused after short term exposure is of little value for distinguishing between carcinogenic and non-carcinogenic oils. PMID:6615701

  19. Mixtures of Uncaria and Tabebuia extracts are potentially chemopreventive in CBA/Ca mice: a long-term experiment.

    PubMed

    Budán, Ferenc; Szabó, István; Varjas, Tímea; Nowrasteh, Ghodratollah; Dávid, Tamás; Gergely, Péter; Varga, Zsuzsa; Molnár, Kornélia; Kádár, Balázs; Orsós, Zsuzsa; Kiss, István; Ember, István

    2011-04-01

    A long-term experimental animal model was developed by our research group for the evaluation of potential chemopreventive effects. The inhibitory effects of agents on carcinogen (7,12-dimethylbenz[a]anthracene (DMBA) induced molecular epidemiological biomarkers, in this case the expression of key onco/suppressor genes were investigated. The expression pattern of c-myc, Ha-ras, Bcl-2, K-ras protooncogene and p53 tumour suppressor gene were studied to elucidate early carcinogenic and potential chemopreventive effects. The consumption of so-called Claw of Dragon tea (CoD™ tea) containing the bark of Uncaria guianensis, Cat's Claw (Uncaria sp. U. tomentosa) and Palmer trumpet-tree (Tabebuia sp. T. avellanedae) was able to decrease the DMBA-induced onco/suppressor gene overexpression in a short-term animal experiment. In a following study CBA/Ca mice were treated with 20 mg/kg bw DMBA intraperitoneally (i.p.) and the expression patterns of onco/suppressor genes were examined at several time intervals. According to the examined gene expression patterns in this long-term experiment the chemopreventive effect of CoD™ tea consumption could be confirmed.

  20. SAMP8 mice have altered hippocampal gene expression in long term potentiation, phosphatidylinositol signaling, and endocytosis pathways.

    PubMed

    Armbrecht, Harvey J; Siddiqui, Akbar M; Green, Michael; Farr, Susan A; Kumar, Vijaya B; Banks, William A; Patrick, Ping; Shah, Gul N; Morley, John E

    2014-01-01

    The senescence-accelerated mouse (SAMP8) strain exhibits decreased learning and memory and increased amyloid beta (Aβ) peptide accumulation at 12 months. To detect differences in gene expression in SAMP8 mice, we used a control mouse that was a 50% cross between SAMP8 and CD-1 mice and which showed no memory deficits (50% SAMs). We then compared gene expression in the hippocampus of 4- and 12-month-old SAMP8 and control mice using Affymetrix gene arrays. At 12 months, but not at 4 months, pathway analysis revealed significant differences in the long term potentiation (6 genes), phosphatidylinositol signaling (6 genes), and endocytosis (10 genes) pathways. The changes in long term potentiation included mitogen-activated protein kinase (MAPK) signaling (N-ras, cAMP responsive element binding protein [CREB], protein phosphatase inhibitor 1) and Ca-dependent signaling (inositol triphosphate [ITP] receptors 1 and 2 and phospholipase C). Changes in phosphatidylinositol signaling genes suggested altered signaling through phosphatidylinositol-3-kinase, and Western blotting revealed phosphorylation changes in serine/threonine protein kinase AKT and 70S6K. Changes in the endocytosis pathway involved genes related to clathrin-mediated endocytosis (dynamin and clathrin). Endocytosis is required for receptor recycling, is involved in Aβ metabolism, and is regulated by phosphatidylinositol signaling. In summary, these studies demonstrate altered gene expression in 3 SAMP8 hippocampal pathways associated with memory formation and consolidation. These pathways might provide new therapeutic targets in addition to targeting Aβ metabolism itself.

  1. Long-term effects of early-life environmental manipulations in rodents and primates: Potential animal models in depression research.

    PubMed

    Pryce, Christopher R; Rüedi-Bettschen, Daniela; Dettling, Andrea C; Weston, Anna; Russig, Holger; Ferger, Boris; Feldon, Joram

    2005-01-01

    Depression is one of the most common human illnesses and is of immense clinical and economic significance. Knowledge of the neuro-psychology, -biology and -pharmacology of depression is limited, as is the efficacy of antidepressant treatment. In terms of depression aetiology, whilst the evidence for causal mechanisms is sparse, some genomic and environmental factors associated with increased vulnerability have been identified. With regards to the latter, the environments in which human infants and children develop are fundamental to how they develop, and parental loss, emotional and physical neglect, and abuse have been shown to be associated with: traits of depression, traits of predisposition to depression triggered by subsequent life events, and associated physiological abnormalities, across the life span. Studies of postnatal environmental manipulations in rodents and primates can potentially yield evidence that abnormal early-life experience leading to dysfunction of the neurobiology, physiology and behaviour of emotion is a general mammalian characteristic, and therefore, that this approach can be used to develop animal models for depression research, with aetiological, face, construct and predictive validity. The establishment of models with such validity, if at all achievable, will require a sophisticated combination of (1) appropriate postnatal manipulations that induce acute stress responses in the infant brain which in turn lead to long-term neurobiological consequences, and (2) appropriate behavioural and physiological assays to identify and quantify any depression-like phenotypes resulting from these long-term neurobiological phenotypes. Here, we review some of the evidence-positive and negative-that neglect-like environments in rat pups and monkey infants lead to long-term, depression-like behavioural traits of reduced motivation for reward and impaired coping with adversity, and to altered activity in relevant physiological homeostatic systems. PMID

  2. Ampakines promote spine actin polymerization, long-term potentiation, and learning in a mouse model of Angelman Syndrome

    PubMed Central

    Baudry, Michel; Kramar, Eniko; Xu, Xiaobo; Zadran, Homera; Moreno, Stephanie; Lynch, Gary; Gall, Christine; Bi, Xiaoning

    2012-01-01

    Angelman syndrome (AS) is a neurodevelopmental disorder largely due to abnormal maternal expression of the UBE3A gene leading to the deletion of E6-associated protein. AS subjects have severe cognitive impairments for which there are no therapeutic interventions. Mouse models (knockouts of the maternal Ube3a gene: ‘AS mice’) of the disorder have substantial deficits in long-term potentiation (LTP) and learning. Here we report a clinically plausible pharmacological treatment that ameliorates both deficits. AS mice were injected ip twice daily for 5 days with vehicle or the ampakine CX929; drugs of this type enhance fast EPSCs by positively modulating AMPA receptors. Theta burst stimulation (TBS) produced a normal enhancement of field EPSPs in hippocampal slices prepared from vehicle-treated AS mice but LTP decreased steadily to baseline; however, LTP in slices from ampakine-treated AS mice stabilized at levels found in wild-type controls. TBS-induced actin polymerization within dendritic spines, an essential event for stabilizing LTP, was severely impaired in slices from vehicle-treated AS mice but not in those from ampakine-treated AS mice. Long-term memory scores in a fear conditioning paradigm were reduced by 50% in vehicle-treated AS mice but were comparable to values for littermate controls in the ampakine-treated AS mice. We propose that AS is associated with a profound defect in activity-driven spine cytoskeletal reorganization, resulting in a loss of the synaptic plasticity required for the encoding of long-term memory. Notably, the spine abnormality along with the LTP and learning impairments can be reduced by a minimally invasive drug treatment. PMID:22525571

  3. Role of constitutive calcium-independent phospholipase A2 beta in hippocampo-prefrontal cortical long term potentiation and spatial working memory.

    PubMed

    Shalini, Suku-Maran; Chew, Wee-Siong; Rajkumar, Ramamoorthy; Dawe, Gavin S; Ong, Wei-Yi

    2014-12-01

    Calcium independent phospholipase A2 (iPLA2) is an 85 kDa protein that catalyzes the hydrolysis of the sn-2 acyl ester bond of glycerophospholipids to liberate free fatty acids and lysophospholipids. In this study, we determined the role of constitutive iPLA2β in long term potentiation (LTP) of the hippocampo-prefrontal cortical pathway in vivo. We also examined the effect of iPLA2β knockdown using the rewarded alternation in T-maze task, a test of spatial working memory which is dependent on this pathway. Intracortical injection of an inhibitor to iPLA2, bromoenol lactone (BEL) or antisense oligonucleotide to iPLA2β in the prefrontal cortex abolished induction of hippocampo-prefrontal cortical LTP. Moreover, iPLA2 inhibition and antisense knockdown resulted in increased errors in the rewarded alternation in T-maze task, indicating negative effects on spatial working memory. BEL or antisense injection did not produce DNA fragmentation in the cortex as demonstrated by TUNEL assay. Results confirm a role of constitutive iPLA2β in hippocampo-prefrontal cortical synaptic plasticity in vivo, and add to previous observations of a role of iPLA2 in hippocampal LTP in vitro, and long-term memory retrieval. They may be relevant in Alzheimer's disease, and other neurodegenerative conditions that are associated with changes in iPLA2.

  4. The E3 ligase APC/C-Cdh1 is required for associative fear memory and long-term potentiation in the amygdala of adult mice.

    PubMed

    Pick, Joseph E; Malumbres, Marcos; Klann, Eric

    2012-12-14

    The anaphase promoting complex/cyclosome (APC/C) is an E3 ligase regulated by Cdh1. Beyond its role in controlling cell cycle progression, APC/C-Cdh1 has been detected in neurons and plays a role in long-lasting synaptic plasticity and long-term memory. Herein, we further examined the role of Cdh1 in synaptic plasticity and memory by generating knockout mice where Cdh1 was conditionally eliminated from the forebrain post-developmentally. Although spatial learning and memory in the Morris water maze (MWM) was normal, the Cdh1 conditional knockout (cKO) mice displayed enhanced reversal learning in the MWM and in a water-based Y maze. In addition, we found that the Cdh1 cKO mice had impaired associative fear memory and exhibited impaired long-term potentiation (LTP) in amygdala slices. Finally, we observed increased expression of Shank1 and NR2A expression in amygdalar slices from the Cdh1 cKO mice following the induction of LTP, suggesting a possible molecular mechanism underlying the behavioral and synaptic plasticity impairments displayed in these mice. Our findings are consistent with a role for the APC/C-Cdh1 in fear memory and synaptic plasticity in the amygdala.

  5. Long term in-line sludge storage in wastewater treatment plants: the potential for phosphorus release.

    PubMed

    Johannessen, Erik; Eikum, Arild Schanke; Krogstad, Tore

    2012-12-01

    Phosphorus removal in on-site wastewater treatment plants is normally obtained by chemical precipitation. Aluminium-based chemicals are the favoured coagulants as they are not affected by redox potential. On-site wastewater treatment package plants do not have separate sludge treatment facilities, and sludge is normally collected on an annual basis. This can potentially increase the risk of phosphorus release into the water phase, subsequently reducing treatment efficiency. This study aimed to detect release of phosphorus as a result of chemical and biological processes. Variables in the study were time, aluminium dosage and pH. Wastewater sludge was monitored for 46 weeks to investigate the different mechanisms of phosphorus release and the longevity of the aluminium treatment involving varying aluminium dosages. Phosphorus compounds were analysed based on a modified Psenner sequential fractionation method. Both pH and aluminium dosage affect the longevity of the phosphorus retention of chemically precipitated wastewater sludge, where sufficient longevity is obtained with pH control and increased aluminium dosages. Chemical dosages similar to what is considered normal levels are sufficient to retain the phosphorus in the sludge for annual sludge collection intervals. Release of soluble phosphorus was attributed to microbial activity and crystallization of Al-hydroxide complexes. PMID:23437673

  6. Long-term expansion, enhanced chondrogenic potential, and suppression of endochondral ossification of adult human MSCs via WNT signaling modulation.

    PubMed

    Narcisi, Roberto; Cleary, Mairéad A; Brama, Pieter A J; Hoogduijn, Martin J; Tüysüz, Nesrin; ten Berge, Derk; van Osch, Gerjo J V M

    2015-03-10

    Mesenchymal stem cells (MSCs) are a potential source of chondrogenic cells for the treatment of cartilage disorders, but loss of chondrogenic potential during in vitro expansion and the propensity of cartilage to undergo hypertrophic maturation impede their therapeutic application. Here we report that the signaling protein WNT3A, in combination with FGF2, supports long-term expansion of human bone marrow-derived MSCs. The cells retained their chondrogenic potential and other phenotypic and functional properties of multipotent MSCs, which were gradually lost in the absence of WNT3A. Moreover, we discovered that endogenous WNT signals are the main drivers of the hypertrophic maturation that follows chondrogenic differentiation. Inhibition of WNT signals during differentiation prevented calcification and maintained cartilage properties following implantation in a mouse model. By maintaining potency during expansion and preventing hypertrophic maturation following differentiation, the modulation of WNT signaling removes two major obstacles that impede the clinical application of MSCs in cartilage repair.

  7. Possible long term effects of chemical warfare using visual evoked potentials.

    PubMed

    Riazi, Abbas; Hafezi, Rhamatollah; Babaei, Mahmoud; Naderi, Mostafa

    2014-09-01

    Some studies have already addressed the effects of occupational organic solvent exposure on the visually evoked potentials (VEPs). Visual system is an important target for Sulphur Mustard (SM) toxicity. A number of Iranian victims of Sulphur Mustard (SM) agent were apprehensive about the delay effect of SM on their vision and a possible delay effect of SM on their visual cortex. This investigation was performed on 34 individuals with a history of chemical exposure and a control group of 15 normal people. The Toennies electro-diagnosis device was used and its signals were saved as the latencies. The mean of N75, N140 and P100 of victims of chemical warfare (VCWs) and control group indicated no significant results (P>0.05). The VCWs did not show any visual symptoms and there was no clear deficit in their VEPs.

  8. Human Onchocerciasis: Modelling the Potential Long-term Consequences of a Vaccination Programme

    PubMed Central

    Turner, Hugo C.; Walker, Martin; Lustigman, Sara; Taylor, David W.; Basáñez, María-Gloria

    2015-01-01

    Background Currently, the predominant onchocerciasis control strategy in Africa is annual mass drug administration (MDA) with ivermectin. However, there is a consensus among the global health community, supported by mathematical modelling, that onchocerciasis in Africa will not be eliminated within proposed time frameworks in all endemic foci with only annual MDA, and novel and alternative strategies are urgently needed. Furthermore, use of MDA with ivermectin is already compromised in large areas of central Africa co-endemic with Loa loa, and there are areas where suboptimal or atypical responses to ivermectin have been documented. An onchocerciasis vaccine would be highly advantageous in these areas. Methodology/Principal Findings We used a previously developed onchocerciasis transmission model (EPIONCHO) to investigate the impact of vaccination in areas where loiasis and onchocerciasis are co-endemic and ivermectin is contraindicated. We also explore the potential influence of a vaccination programme on infection resurgence in areas where local elimination has been successfully achieved. Based on the age range included in the Expanded Programme on Immunization (EPI), the vaccine was assumed to target 1 to 5 year olds. Our modelling results indicate that the deployment of an onchocerciasis vaccine would have a beneficial impact in onchocerciasis–loiasis co-endemic areas, markedly reducing microfilarial load in the young (under 20 yr) age groups. Conclusions/Significance An onchocerciasis prophylactic vaccine would reduce the onchocerciasis disease burden in populations where ivermectin cannot be administered safely. Moreover, a vaccine could substantially decrease the chance of re-emergence of Onchocerca volvulus infection in areas where it is deemed that MDA with ivermectin can be stopped. Therefore, a vaccine would protect the substantial investments made by present and past onchocerciasis control programmes, decreasing the chance of disease recrudescence and

  9. Long term, stable brain machine interface performance using local field potentials and multiunit spikes

    PubMed Central

    Flint, Robert D.; Wright, Zachary A.; Scheid, Michael R.; Slutzky, Marc W

    2014-01-01

    Objective Brain machine interfaces (BMIs) have the potential to restore movement to people with paralysis. However, a clinically-viable BMI must enable consistently accurate control over time spans ranging from years to decades, which has not yet been demonstrated. Most BMIs that use single-unit spikes as inputs will experience degraded performance over time without frequent decoder re-training. Two other signals, local field potentials (LFPs) and multi-unit spikes (MSPs), may offer greater reliability over long periods and better performance stability than single-unit spikes. Here, we demonstrate that LFPs can be used in a biomimetic BMI to control a computer cursor. Approach We implanted two rhesus macaques with intracortical microelectrodes in primary motor cortex. We recorded LFP and MSP signals from the monkeys while they performed a continuous reaching task, moving a cursor to randomly-placed targets on a computer screen. We then used the LFP and MSP signals to construct biomimetic decoders for control of the cursor. Main results Both monkeys achieved high-performance, continuous control that remained stable or improved over nearly 12 months using an LFP decoder that was not retrained or adapted. In parallel, the monkeys used MSPs to control a BMI without retraining or adaptation and had similar or better performance, and that predominantly remained stable over more than six months. In contrast to their stable online control, both LFP and MSP signals showed substantial variability when used offline to predict hand movements. Significance Our results suggest that the monkeys were able to stabilize the relationship between neural activity and cursor movement during online BMI control, despite variability in the relationship between neural activity and hand movements. PMID:23918061

  10. Long term, stable brain machine interface performance using local field potentials and multiunit spikes

    NASA Astrophysics Data System (ADS)

    Flint, Robert D.; Wright, Zachary A.; Scheid, Michael R.; Slutzky, Marc W.

    2013-10-01

    Objective. Brain machine interfaces (BMIs) have the potential to restore movement to people with paralysis. However, a clinically-viable BMI must enable consistently accurate control over time spans ranging from years to decades, which has not yet been demonstrated. Most BMIs that use single-unit spikes as inputs will experience degraded performance over time without frequent decoder re-training. Two other signals, local field potentials (LFPs) and multi-unit spikes (MSPs), may offer greater reliability over long periods and better performance stability than single-unit spikes. Here, we demonstrate that LFPs can be used in a biomimetic BMI to control a computer cursor. Approach. We implanted two rhesus macaques with intracortical microelectrodes in primary motor cortex. We recorded LFP and MSP signals from the monkeys while they performed a continuous reaching task, moving a cursor to randomly-placed targets on a computer screen. We then used the LFP and MSP signals to construct biomimetic decoders for control of the cursor. Main results. Both monkeys achieved high-performance, continuous control that remained stable or improved over nearly 12 months using an LFP decoder that was not retrained or adapted. In parallel, the monkeys used MSPs to control a BMI without retraining or adaptation and had similar or better performance, and that predominantly remained stable over more than six months. In contrast to their stable online control, both LFP and MSP signals showed substantial variability when used offline to predict hand movements. Significance. Our results suggest that the monkeys were able to stabilize the relationship between neural activity and cursor movement during online BMI control, despite variability in the relationship between neural activity and hand movements.

  11. Effects of tetrahydrohyperforin in mouse hippocampal slices: neuroprotection, long-term potentiation and TRPC channels.

    PubMed

    Montecinos-Oliva, C; Schuller, A; Parodi, J; Melo, F; Inestrosa, N C

    2014-01-01

    Tetrahydrohyperforin (IDN5706) is a semi-synthetic compound derived from hyperforin (IDN5522) and is the main active principle of St. John's Wort. IDN5706 has shown numerous beneficial effects when administered to wild-type and double transgenic (APPswe/PSEN1ΔE9) mice that model Alzheimer's disease. However, its mechanism of action is currently unknown. Toward this end, we analysed field excitatory postsynaptic potentials (fEPSPs) in mouse hippocampal slices incubated with IDN5706 and in the presence of the TRPC3/6/7 activator 1-oleoyl-2-acetyl-sn-glycerol (OAG), the TRPC channel blocker SKF96365, and neurotoxic amyloid β-protein (Aβ) oligomers. To study spatial memory, Morris water maze (MWM) behavioural tests were conducted on wild-type mice treated with IDN5706 and SKF96365. In silico studies were conducted to predict a potential pharmacophore. IDN5706 and OAG had a similar stimulating effect on fEPSPs, which was inhibited by SKF96365. IDN5706 protected from reduced fEPSPs induced by Aβ oligomers. IDN5706 improved spatial memory in wild-type mice, an effect that was counteracted by co-administration of SKF96365. Our in silico studies suggest strong pharmacophore similarity of IDN5706 and other reported TRPC6 activators (IDN5522, OAG and Hyp9). We propose that the effect of IDN5706 is mediated through activation of the TRPC3/6/7 channel subfamily. The unveiling of the drug's mechanism of action is a necessary step toward the clinical use of IDN5706 in Alzheimer's disease. PMID:25039785

  12. GluA2-dependent AMPA receptor endocytosis and the decay of early and late long-term potentiation: possible mechanisms for forgetting of short- and long-term memories.

    PubMed

    Hardt, Oliver; Nader, Karim; Wang, Yu-Tian

    2014-01-01

    The molecular processes involved in establishing long-term potentiation (LTP) have been characterized well, but the decay of early and late LTP (E-LTP and L-LTP) is poorly understood. We review recent advances in describing the mechanisms involved in maintaining LTP and homeostatic plasticity. We discuss how these phenomena could relate to processes that might underpin the loss of synaptic potentiation over time, and how they might contribute to the forgetting of short-term and long-term memories. We propose that homeostatic downscaling mediates the loss of E-LTP, and that metaplastic parameters determine the decay rate of L-LTP, while both processes require the activity-dependent removal of postsynaptic GluA2-containing AMPA receptors. PMID:24298143

  13. Event-related potential correlates of long-term memory for briefly presented faces.

    PubMed

    Joyce, Carrie A; Kutas, Marta

    2005-05-01

    Electrophysiological studies have investigated the nature of face recognition in a variety of paradigms; some have contrasted famous and novel faces in explicit memory paradigms, others have repeated faces to examine implicit memory/priming. If the general finding that implicit memory can last for up to several months also holds for novel faces, a reliable measure of it could have practical application for eyewitness testimony, given that explicit measures of eyewitness memory have at times proven fallible. The current study aimed to determine whether indirect behavioral and electrophysiological measures might yield reliable estimates of face memory over longer intervals than have typically been obtained with priming manipulations. Participants were shown 192 faces and then tested for recognition at four test delays ranging from immediately up to 1 week later. Three event-related brain potential components (e.g., N250r, N400f, and LPC) varied with memory measures although only the N250r varied regardless of explicit recognition, that is, with both repetition and recognition. PMID:15904542

  14. The Greenville Fault: preliminary estimates of its long-term creep rate and seismic potential

    USGS Publications Warehouse

    Lienkaemper, James J.; Barry, Robert G.; Smith, Forrest E.; Mello, Joseph D.; McFarland, Forrest S.

    2013-01-01

    Once assumed locked, we show that the northern third of the Greenville fault (GF) creeps at 2 mm/yr, based on 47 yr of trilateration net data. This northern GF creep rate equals its 11-ka slip rate, suggesting a low strain accumulation rate. In 1980, the GF, easternmost strand of the San Andreas fault system east of San Francisco Bay, produced a Mw5.8 earthquake with a 6-km surface rupture and dextral slip growing to ≥2 cm on cracks over a few weeks. Trilateration shows a 10-cm post-1980 transient slip ending in 1984. Analysis of 2000-2012 crustal velocities on continuous global positioning system stations, allows creep rates of ~2 mm/yr on the northern GF, 0-1 mm/yr on the central GF, and ~0 mm/yr on its southern third. Modeled depth ranges of creep along the GF allow 5-25% aseismic release. Greater locking in the southern two thirds of the GF is consistent with paleoseismic evidence there for large late Holocene ruptures. Because the GF lacks large (>1 km) discontinuities likely to arrest higher (~1 m) slip ruptures, we expect full-length (54-km) ruptures to occur that include the northern creeping zone. We estimate sufficient strain accumulation on the entire GF to produce Mw6.9 earthquakes with a mean recurrence of ~575 yr. While the creeping 16-km northern part has the potential to produce a Mw6.2 event in 240 yr, it may rupture in both moderate (1980) and large events. These two-dimensional-model estimates of creep rate along the southern GF need verification with small aperture surveys.

  15. The global economic long-term potential of modern biomass in a climate-constrained world

    NASA Astrophysics Data System (ADS)

    Klein, David; Humpenöder, Florian; Bauer, Nico; Dietrich, Jan Philipp; Popp, Alexander; Bodirsky, Benjamin Leon; Bonsch, Markus; Lotze-Campen, Hermann

    2014-07-01

    Low-stabilization scenarios consistent with the 2 °C target project large-scale deployment of purpose-grown lignocellulosic biomass. In case a GHG price regime integrates emissions from energy conversion and from land-use/land-use change, the strong demand for bioenergy and the pricing of terrestrial emissions are likely to coincide. We explore the global potential of purpose-grown lignocellulosic biomass and ask the question how the supply prices of biomass depend on prices for greenhouse gas (GHG) emissions from the land-use sector. Using the spatially explicit global land-use optimization model MAgPIE, we construct bioenergy supply curves for ten world regions and a global aggregate in two scenarios, with and without a GHG tax. We find that the implementation of GHG taxes is crucial for the slope of the supply function and the GHG emissions from the land-use sector. Global supply prices start at 5 GJ-1 and increase almost linearly, doubling at 150 EJ (in 2055 and 2095). The GHG tax increases bioenergy prices by 5 GJ-1 in 2055 and by 10 GJ-1 in 2095, since it effectively stops deforestation and thus excludes large amounts of high-productivity land. Prices additionally increase due to costs for N2O emissions from fertilizer use. The GHG tax decreases global land-use change emissions by one-third. However, the carbon emissions due to bioenergy production increase by more than 50% from conversion of land that is not under emission control. Average yields required to produce 240 EJ in 2095 are roughly 600 GJ ha-1 yr-1 with and without tax.

  16. Repeated Isoflurane Exposures Impair Long-Term Potentiation and Increase Basal GABAergic Activity in the Basolateral Amygdala

    PubMed Central

    Long II, Robert P.; Aroniadou-Anderjaska, Vassiliki; Prager, Eric M.; Pidoplichko, Volodymyr I.; Figueiredo, Taiza H.; Braga, Maria F. M.

    2016-01-01

    After surgery requiring general anesthesia, patients often experience emotional disturbances, but it is unclear if this is due to anesthetic exposure. In the present study, we examined whether isoflurane anesthesia produces long-term pathophysiological alterations in the basolateral amygdala (BLA), a brain region that plays a central role in emotional behavior. Ten-week-old, male rats were administered either a single, 1 h long isoflurane (1.5%) anesthesia or three, 1 h long isoflurane exposures, separated by 48 h. Long-term potentiation (LTP) and spontaneous GABAergic activity in the BLA were studied 1 day, 1 week, and 1 month later. Single isoflurane anesthesia had no significant effect on the magnitude of LTP. In contrast, after repeated isoflurane exposures, LTP was dramatically impaired at both 1 day and 1 week after the last exposure but was restored by 1 month after the exposures. Spontaneous GABAA receptor-mediated IPSCs were increased at 1 day and 1 week after repeated exposures but had returned to control levels by 1 month after exposure. Thus, repeated exposures to isoflurane cause a long-lasting—but not permanent—impairment of synaptic plasticity in the BLA, which could be due to increased basal GABAergic activity. These pathophysiological alterations may produce emotional disturbances and impaired fear-related learning. PMID:27313904

  17. Repeated Isoflurane Exposures Impair Long-Term Potentiation and Increase Basal GABAergic Activity in the Basolateral Amygdala.

    PubMed

    Long Ii, Robert P; Aroniadou-Anderjaska, Vassiliki; Prager, Eric M; Pidoplichko, Volodymyr I; Figueiredo, Taiza H; Braga, Maria F M

    2016-01-01

    After surgery requiring general anesthesia, patients often experience emotional disturbances, but it is unclear if this is due to anesthetic exposure. In the present study, we examined whether isoflurane anesthesia produces long-term pathophysiological alterations in the basolateral amygdala (BLA), a brain region that plays a central role in emotional behavior. Ten-week-old, male rats were administered either a single, 1 h long isoflurane (1.5%) anesthesia or three, 1 h long isoflurane exposures, separated by 48 h. Long-term potentiation (LTP) and spontaneous GABAergic activity in the BLA were studied 1 day, 1 week, and 1 month later. Single isoflurane anesthesia had no significant effect on the magnitude of LTP. In contrast, after repeated isoflurane exposures, LTP was dramatically impaired at both 1 day and 1 week after the last exposure but was restored by 1 month after the exposures. Spontaneous GABAA receptor-mediated IPSCs were increased at 1 day and 1 week after repeated exposures but had returned to control levels by 1 month after exposure. Thus, repeated exposures to isoflurane cause a long-lasting-but not permanent-impairment of synaptic plasticity in the BLA, which could be due to increased basal GABAergic activity. These pathophysiological alterations may produce emotional disturbances and impaired fear-related learning.

  18. Repeated Isoflurane Exposures Impair Long-Term Potentiation and Increase Basal GABAergic Activity in the Basolateral Amygdala.

    PubMed

    Long Ii, Robert P; Aroniadou-Anderjaska, Vassiliki; Prager, Eric M; Pidoplichko, Volodymyr I; Figueiredo, Taiza H; Braga, Maria F M

    2016-01-01

    After surgery requiring general anesthesia, patients often experience emotional disturbances, but it is unclear if this is due to anesthetic exposure. In the present study, we examined whether isoflurane anesthesia produces long-term pathophysiological alterations in the basolateral amygdala (BLA), a brain region that plays a central role in emotional behavior. Ten-week-old, male rats were administered either a single, 1 h long isoflurane (1.5%) anesthesia or three, 1 h long isoflurane exposures, separated by 48 h. Long-term potentiation (LTP) and spontaneous GABAergic activity in the BLA were studied 1 day, 1 week, and 1 month later. Single isoflurane anesthesia had no significant effect on the magnitude of LTP. In contrast, after repeated isoflurane exposures, LTP was dramatically impaired at both 1 day and 1 week after the last exposure but was restored by 1 month after the exposures. Spontaneous GABAA receptor-mediated IPSCs were increased at 1 day and 1 week after repeated exposures but had returned to control levels by 1 month after exposure. Thus, repeated exposures to isoflurane cause a long-lasting-but not permanent-impairment of synaptic plasticity in the BLA, which could be due to increased basal GABAergic activity. These pathophysiological alterations may produce emotional disturbances and impaired fear-related learning. PMID:27313904

  19. Potential long-term consequences of fad diets on health, cancer, and longevity: lessons learned from model organism studies.

    PubMed

    Ruden, Douglas M; Rasouli, Parsa; Lu, Xiangyi

    2007-06-01

    While much of the third world starves, many in the first world are undergoing an obesity epidemic, and the related epidemics of type II diabetes, heart disease, and other diseases associated with obesity. The amount of economic wealth being directly related to a decline in health by obesity is ironic because rich countries contribute billions of dollars to improve the health of their citizens. Nevertheless, nutritional experiments in model organisms such as yeast, C. elegans, Drosophila, and mice confirm that "caloric restriction" (CR), which is defined generally as a 30-40% decrease in caloric intake, a famine-like condition for humans seen only in the poorest of countries, promotes good health and increases longevity in model organisms. Because caloric restriction, and dieting in general, requires a great deal of will power to deal with the feelings of deprivation, many fad diets, such as the Atkins, South Beach, and Protein Power, have been developed which allow people to lose weight purportedly without the severe feelings of deprivation. However, the long-term effects of such fad diets are not known and few experiments have been performed in the laboratory to investigate possible side affects and adverse consequences. In this paper, we review studies with fad-like dietary conditions in humans and model organisms, and we propose a "Dietary Ames Test" to rapidly screen fad diets, dietary supplements, and drugs for potential long-term health consequences in model organisms.

  20. Decellularized Allogeneic Heart Valves Demonstrate Self-Regeneration Potential after a Long-Term Preclinical Evaluation

    PubMed Central

    Iop, Laura; Bonetti, Antonella; Naso, Filippo; Rizzo, Stefania; Cagnin, Stefano; Bianco, Roberto; Lin, Carlo Dal; Martini, Paolo; Poser, Helen; Franci, Paolo; Lanfranchi, Gerolamo; Busetto, Roberto; Spina, Michel; Basso, Cristina; Marchini, Maurizio; Gandaglia, Alessandro

    2014-01-01

    Tissue-engineered heart valves are proposed as novel viable replacements granting longer durability and growth potential. However, they require extensive in vitro cell-conditioning in bioreactor before implantation. Here, the propensity of non-preconditioned decellularized heart valves to spontaneous in body self-regeneration was investigated in a large animal model. Decellularized porcine aortic valves were evaluated for right ventricular outflow tract (RVOT) reconstruction in Vietnamese Pigs (n = 11) with 6 (n = 5) and 15 (n = 6) follow-up months. Repositioned native valves (n = 2 for each time) were considered as control. Tissue and cell components from explanted valves were investigated by histology, immunohistochemistry, electron microscopy, and gene expression. Most substitutes constantly demonstrated in vivo adequate hemodynamic performances and ex vivo progressive repopulation during the 15 implantation months without signs of calcifications, fibrosis and/or thrombosis, as revealed by histological, immunohistochemical, ultrastructural, metabolic and transcriptomic profiles. Colonizing cells displayed native-like phenotypes and actively synthesized novel extracellular matrix elements, as collagen and elastin fibers. New mature blood vessels, i.e. capillaries and vasa vasorum, were identified in repopulated valves especially in the medial and adventitial tunicae of regenerated arterial walls. Such findings correlated to the up-regulated vascular gene transcription. Neoinnervation hallmarks were appreciated at histological and ultrastructural levels. Macrophage populations with reparative M2 phenotype were highly represented in repopulated valves. Indeed, no aspects of adverse/immune reaction were revealed in immunohistochemical and transcriptomic patterns. Among differentiated elements, several cells were identified expressing typical stem cell markers of embryonic, hematopoietic, neural and mesenchymal lineages in significantly higher number

  1. Decellularized allogeneic heart valves demonstrate self-regeneration potential after a long-term preclinical evaluation.

    PubMed

    Iop, Laura; Bonetti, Antonella; Naso, Filippo; Rizzo, Stefania; Cagnin, Stefano; Bianco, Roberto; Dal Lin, Carlo; Martini, Paolo; Poser, Helen; Franci, Paolo; Lanfranchi, Gerolamo; Busetto, Roberto; Spina, Michel; Basso, Cristina; Marchini, Maurizio; Gandaglia, Alessandro; Ortolani, Fulvia; Gerosa, Gino

    2014-01-01

    Tissue-engineered heart valves are proposed as novel viable replacements granting longer durability and growth potential. However, they require extensive in vitro cell-conditioning in bioreactor before implantation. Here, the propensity of non-preconditioned decellularized heart valves to spontaneous in body self-regeneration was investigated in a large animal model. Decellularized porcine aortic valves were evaluated for right ventricular outflow tract (RVOT) reconstruction in Vietnamese Pigs (n = 11) with 6 (n = 5) and 15 (n = 6) follow-up months. Repositioned native valves (n = 2 for each time) were considered as control. Tissue and cell components from explanted valves were investigated by histology, immunohistochemistry, electron microscopy, and gene expression. Most substitutes constantly demonstrated in vivo adequate hemodynamic performances and ex vivo progressive repopulation during the 15 implantation months without signs of calcifications, fibrosis and/or thrombosis, as revealed by histological, immunohistochemical, ultrastructural, metabolic and transcriptomic profiles. Colonizing cells displayed native-like phenotypes and actively synthesized novel extracellular matrix elements, as collagen and elastin fibers. New mature blood vessels, i.e. capillaries and vasa vasorum, were identified in repopulated valves especially in the medial and adventitial tunicae of regenerated arterial walls. Such findings correlated to the up-regulated vascular gene transcription. Neoinnervation hallmarks were appreciated at histological and ultrastructural levels. Macrophage populations with reparative M2 phenotype were highly represented in repopulated valves. Indeed, no aspects of adverse/immune reaction were revealed in immunohistochemical and transcriptomic patterns. Among differentiated elements, several cells were identified expressing typical stem cell markers of embryonic, hematopoietic, neural and mesenchymal lineages in significantly higher number

  2. Long-term effect of temperature on bioaccumulation of dietary metals and metallothionein induction in Sparus aurata.

    PubMed

    Guinot, Diana; Ureña, Rocío; Pastor, Agustín; Varó, Inmaculada; del Ramo, Jose; Torreblanca, Amparo

    2012-06-01

    Previous studies have demonstrated that the commercial feed of aquacultured fish contains trace amounts of toxic and essential metals which can accumulate in tissues and finally be ingested by consumers. Recently rising temperatures, associated to the global warming phenomenon, have been reported as a factor to be taken into consideration in ecotoxicology, since temperature-dependent alterations in bioavailability, toxicokinetics and biotransformation rates can be expected. Sparus aurata were kept at 22°C, 27°C and 30°C for 3 months in order to determine the temperature effect on metallothionein induction and metal bioaccumulation from a non-experimentally contaminated commercial feed. A significant temperature-dependent accumulation of cadmium (Cd), copper (Cu), mercury (Hg), zinc (Zn), lead (Pb) and iron (Fe) was found in liver, together with that of manganese (Mn), Fe and Zn in muscle. Hg presented the highest bioaccumulation factor, and essential metal homeostasis was disturbed in both tissues at warm temperatures. An enhancement of hepatic metallothionein induction was found in fish exposed to the highest temperature.

  3. Electrical high-frequency stimulation of the human thoracolumbar fascia evokes long-term potentiation-like pain amplification.

    PubMed

    Schilder, Andreas; Magerl, Walter; Hoheisel, Ulrich; Klein, Thomas; Treede, Rolf-Detlef

    2016-10-01

    Nociceptive long-term potentiation, a use dependent increase in synaptic efficacy in the dorsal horn of the spinal cord is thought to contribute to the development of persistent pain states. So far, no study has analyzed the effects of high-frequency stimulation (HFS) of afferents from deep tissues (muscle and fascia) on pain perception in the back in humans. In 16 healthy volunteers, the multifidus muscle and the overlying thoracolumbar fascia were stimulated with electrical high-frequency pulses (5 × 100 pulses at 100 Hz) through bipolar concentric needle electrodes placed at lumbar level (L3/L4). Electrical pain thresholds were lower (P < 0.001) and pain ratings were higher for fascia compared with muscle stimulation (P < 0.05). For both tissues, pain ratings increased significantly across the five 100 Hz trains (from 15 to 22 numerical rating scale for fascia, from 8 to 12 numerical rating scale for muscle; both P < 0.01). Fascia HFS increased fascia pain ratings 2.17 times compared with the unconditioned control site (P < 0.001), but had no significant effect on pain sensitivity of the muscle. The HFS in muscle had no significant effect on muscle pain, but decreased pain sensitivity of the overlying fascia by 20% (P < 0.05). In additional experiments using the same electrodes and followed over >60 minutes post-HFS, potentiation by fascia HFS was similar to that of skin HFS. These findings show that the spinal input from the fascia can induce long-term changes in pain sensitivity for at least 60 minutes making it a candidate potentially contributing to nonspecific low back pain. PMID:27322440

  4. Electrical high-frequency stimulation of the human thoracolumbar fascia evokes long-term potentiation-like pain amplification.

    PubMed

    Schilder, Andreas; Magerl, Walter; Hoheisel, Ulrich; Klein, Thomas; Treede, Rolf-Detlef

    2016-10-01

    Nociceptive long-term potentiation, a use dependent increase in synaptic efficacy in the dorsal horn of the spinal cord is thought to contribute to the development of persistent pain states. So far, no study has analyzed the effects of high-frequency stimulation (HFS) of afferents from deep tissues (muscle and fascia) on pain perception in the back in humans. In 16 healthy volunteers, the multifidus muscle and the overlying thoracolumbar fascia were stimulated with electrical high-frequency pulses (5 × 100 pulses at 100 Hz) through bipolar concentric needle electrodes placed at lumbar level (L3/L4). Electrical pain thresholds were lower (P < 0.001) and pain ratings were higher for fascia compared with muscle stimulation (P < 0.05). For both tissues, pain ratings increased significantly across the five 100 Hz trains (from 15 to 22 numerical rating scale for fascia, from 8 to 12 numerical rating scale for muscle; both P < 0.01). Fascia HFS increased fascia pain ratings 2.17 times compared with the unconditioned control site (P < 0.001), but had no significant effect on pain sensitivity of the muscle. The HFS in muscle had no significant effect on muscle pain, but decreased pain sensitivity of the overlying fascia by 20% (P < 0.05). In additional experiments using the same electrodes and followed over >60 minutes post-HFS, potentiation by fascia HFS was similar to that of skin HFS. These findings show that the spinal input from the fascia can induce long-term changes in pain sensitivity for at least 60 minutes making it a candidate potentially contributing to nonspecific low back pain.

  5. A Primary Cortical Input to Hippocampus Expresses a Pathway-Specific and Endocannabinoid-Dependent Form of Long-Term Potentiation

    PubMed Central

    Wang, Weisheng; Jia, Yousheng; Pham, Danielle T.; Karsten, Carley A.; Merrill, Collin B.; Gall, Christine M.; Piomelli, Daniele

    2016-01-01

    Abstract The endocannabinoid 2-arachidonoyl-sn-glycerol (2-AG), a key modulator of synaptic transmission in mammalian brain, is produced in dendritic spines and then crosses the synaptic junction to depress neurotransmitter release. Here we report that 2-AG-dependent retrograde signaling also mediates an enduring enhancement of glutamate release, as assessed with independent tests, in the lateral perforant path (LPP), one of two cortical inputs to the granule cells of the dentate gyrus. Induction of this form of long-term potentiation (LTP) involved two types of glutamate receptors, changes in postsynaptic calcium, and the postsynaptic enzyme that synthesizes 2-AG. Stochastic optical reconstruction microscopy confirmed that CB1 cannabinoid receptors are localized presynaptically to LPP terminals, while the inhibition or knockout of the receptors eliminated LPP-LTP. Suppressing the enzyme that degrades 2-AG dramatically enhanced LPP potentiation, while overexpressing it produced the opposite effect. Priming with a CB1 agonist markedly reduced the threshold for LTP. Latrunculin A, which prevents actin polymerization, blocked LPP-LTP when applied extracellularly but had no effect when infused postsynaptically into granule cells, indicating that critical actin remodeling resides in the presynaptic compartment. Importantly, there was no evidence for the LPP form of potentiation in the Schaffer-commissural innervation of field CA1 or in the medial perforant path. Peripheral injections of compounds that block or enhance LPP-LTP had corresponding effects on the formation of long-term memory for cues conveyed to the dentate gyrus by the LPP. Together, these results indicate that the encoding of information carried by a principal hippocampal afferent involves an unusual, regionally differentiated form of plasticity. PMID:27517090

  6. A Primary Cortical Input to Hippocampus Expresses a Pathway-Specific and Endocannabinoid-Dependent Form of Long-Term Potentiation.

    PubMed

    Wang, Weisheng; Trieu, Brian H; Palmer, Linda C; Jia, Yousheng; Pham, Danielle T; Jung, Kwang-Mook; Karsten, Carley A; Merrill, Collin B; Mackie, Ken; Gall, Christine M; Piomelli, Daniele; Lynch, Gary

    2016-01-01

    The endocannabinoid 2-arachidonoyl-sn-glycerol (2-AG), a key modulator of synaptic transmission in mammalian brain, is produced in dendritic spines and then crosses the synaptic junction to depress neurotransmitter release. Here we report that 2-AG-dependent retrograde signaling also mediates an enduring enhancement of glutamate release, as assessed with independent tests, in the lateral perforant path (LPP), one of two cortical inputs to the granule cells of the dentate gyrus. Induction of this form of long-term potentiation (LTP) involved two types of glutamate receptors, changes in postsynaptic calcium, and the postsynaptic enzyme that synthesizes 2-AG. Stochastic optical reconstruction microscopy confirmed that CB1 cannabinoid receptors are localized presynaptically to LPP terminals, while the inhibition or knockout of the receptors eliminated LPP-LTP. Suppressing the enzyme that degrades 2-AG dramatically enhanced LPP potentiation, while overexpressing it produced the opposite effect. Priming with a CB1 agonist markedly reduced the threshold for LTP. Latrunculin A, which prevents actin polymerization, blocked LPP-LTP when applied extracellularly but had no effect when infused postsynaptically into granule cells, indicating that critical actin remodeling resides in the presynaptic compartment. Importantly, there was no evidence for the LPP form of potentiation in the Schaffer-commissural innervation of field CA1 or in the medial perforant path. Peripheral injections of compounds that block or enhance LPP-LTP had corresponding effects on the formation of long-term memory for cues conveyed to the dentate gyrus by the LPP. Together, these results indicate that the encoding of information carried by a principal hippocampal afferent involves an unusual, regionally differentiated form of plasticity. PMID:27517090

  7. The effect of positive mood induction on reducing reinstatement fear: Relevance for long term outcomes of exposure therapy

    PubMed Central

    Zbozinek, Tomislav D.; Holmes, Emily A.; Craske, Michelle G.

    2015-01-01

    While exposure therapy is effective in treating anxiety, fear can return after exposure. Return of fear can be understood through mechanisms of extinction learning. One form of return of fear is reinstatement, or, the fear that results from an unsignaled unconditional stimulus (US) presentation after extinction. Though the conditional response (CR; e.g., fear) typically reduces during extinction, the excitatory conditional stimulus (CS+) valence remains negative. The more negative the CS+ valence after the end of extinction, the greater the fear at reinstatement. The current study evaluated the degree to which positive mood induction (positive imagery training; PIT) compared to control (positive verbal training; PVT) before extinction a) decreased CS+ negative valence during extinction and b) reduced reinstatement fear. Compared to PVT, PIT a) increased positive affect, b) decreased post-extinction CS+ negative valence, and c) reduced reinstatement responding as measured by eye blink startle reflex (when shock was used at reinstatement) and self-report fear (regardless of reinstatement US type). Results suggest that increasing positive affect prior to exposure therapy could reduce relapse through reinstatement. PMID:26073498

  8. Metabolic Profile as a Potential Modifier of Long-Term Radiation Effects on Peripheral Lymphocyte Subsets in Atomic Bomb Survivors.

    PubMed

    Yoshida, Kengo; Nakashima, Eiji; Kyoizumi, Seishi; Hakoda, Masayuki; Hayashi, Tomonori; Hida, Ayumi; Ohishi, Waka; Kusunoki, Yoichiro

    2016-09-01

    Immune system impairments reflected by the composition and function of circulating lymphocytes are still observed in atomic bomb survivors, and metabolic abnormalities including altered blood triglyceride and cholesterol levels have also been detected in such survivors. Based on closely related features of immune and metabolic profiles of individuals, we investigated the hypothesis that long-term effects of radiation exposure on lymphocyte subsets might be modified by metabolic profiles in 3,113 atomic bomb survivors who participated in health examinations at the Radiation Effect Research Foundation, Hiroshima and Nagasaki, in 2000-2002. The lymphocyte subsets analyzed involved T-, B- and NK-cell subsets, and their percentages in the lymphocyte fraction were assessed using flow cytometry. Health examinations included metabolic indicators, body mass index, serum levels of total cholesterol, high-density lipoprotein cholesterol, C-reactive protein and hemoglobin A1c, as well as diabetes and fatty liver diagnoses. Standard regression analyses indicated that several metabolic indicators of obesity/related disease, particularly high-density lipoprotein cholesterol levels, were positively associated with type-1 helper T- and B-cell percentages but were inversely associated with naïve CD4 T and NK cells. A regression analysis adjusted for high-density lipoprotein cholesterol revealed a radiation dose relationship with increasing NK-cell percentage. Additionally, an interaction effect was suggested between radiation dose and C-reactive protein on B-cell percentage with a negative coefficient of the interaction term. Collectively, these findings suggest that radiation exposure and subsequent metabolic profile changes, potentially in relationship to obesity-related inflammation, lead to such long-term alterations in lymphocyte subset composition. Because this study is based on cross-sectional and exploratory analyses, the implications regarding radiation exposure, metabolic

  9. Long-term potential nonlinear predictability of El Niño-La Niña events

    NASA Astrophysics Data System (ADS)

    Astudillo, H. F.; Abarca-del-Río, R.; Borotto, F. A.

    2016-08-01

    We show that the monthly recorded history (1866-2014) of the Southern Oscillation Index (SOI), a descriptor of the El Niño Southern Oscillation (ENSO) phenomenon, can be correctly described as a dynamic system supporting a potential nonlinear predictability well beyond the spring barrier. Long-term predictability is strongly connected to a detailed knowledge about the topology of the attractor obtained by embedding the SOI index in a wavelet base state space. By utilizing the state orbits on the attractor, we show that the information contained in the SOI is sufficient to provide nonlinear attractor information, allowing the detection of predictability for longer than a year: 2, 3, and 4 years in advance throughout the record with an acceptable error. This is possible due to the fact that the lower-frequency variability of the SOI presents long-term positive autocorrelation. Thus, by using complementary methods, we confirm that the reconstructed attractor of the low-frequency part (lower than 1/year) of SOI time series cannot be attributed to stochastic influences. Furthermore, we establish its multifractality. As an example of the capabilities of the methodology, we investigate a few specific El Niño (1972-1973, 1982-1983, 1997-1998) and La Niña (1973-1973, 1988-1989 and 2010-2011) events. Our results indicate that each of these present several equivalent temporal structures over other eras of these 149 years (1866-2014). Accordingly, none of these cases, including extreme events, presents temporal singularity. We conclude that the methodology's simplicity of implementation and ease of use makes it suitable for studying nonlinear predictability in any area where observations are similar to those describing the ENSO phenomenon.

  10. Drivers, trends, and potential impacts of long-term coastal reclamation in China from 1985 to 2010

    NASA Astrophysics Data System (ADS)

    Tian, Bo; Wu, Wenting; Yang, Zhaoqing; Zhou, Yunxuan

    2016-03-01

    The reclamation of coastal land for agricultural, industrial, and urban land use-a common worldwide practice-has occurred extensively in the coastal region of China. In recent decades, all coastal provinces and metropolises in China have experienced severe coastal reclamation related to land scarcity caused by rapid economic growth and urbanization. However, the value of coastal wetlands and ecosystems has not been well understood and appreciated until recent development of advantageous methods of restoring reclaimed land to coastal wetlands in many developed countries. The overall objective of this study is to provide detailed spatial and temporal distributions of coastal reclamation; analyze drivers such as coastal economy, population growth, and urbanization; and understand the relationships among the drivers and land reclamation. We used long-term Landsat image time series from 1985 to 2010 in 5-year intervals, in combination with remotely sensed image interpretation and spatial analysis, to map the reclamation status and changes across the coastal region of China. The Landsat images time-series analysis was also conducted to evaluate the effects of the economy, population, and urbanization drivers on coastal reclamation. The analysis results indicated that 754,697 ha of coastal wetlands have been reclaimed across all coastal provinces and metropolises from 1985 to 2010, and the trend increased sharply after 2005. High-intensity coastal reclamation was mainly driven by the booming economy, especially after 2000, associated with urbanization and industrial development in China's coastal region; this was closely correlated with the gross domestic product (GDP) per capita. The continuous large-scale coastal reclamation of its coastal region now means China is facing a great challenge, including the enormous loss of vegetated coastal wetlands, negative environmental effects, and potential disaster risks related to coastal flooding under future change climate

  11. Acid Mine Drainage Passive Remediation: Potential Use of Alkaline Clay, Optimal Mixing Ratio and Long Term Impacts

    NASA Astrophysics Data System (ADS)

    Plaza, F.; Liang, X.; Wen, Y.; Perone, H.

    2015-12-01

    Acid mine drainage (AMD) is one of the most adverse environmental problems of the mine industry. Surface water and ground water affected by this pollution are characterized by their acidity and the high content of sulfates and heavy metals. In this study, alkaline clay, an industrial waste with a high pH, which is utilized in the alumina refining process, was used as the remediation material to inhibit pyrite oxidation. Through a series of batch and column experiments, complemented with field measurements and geochemical modeling, three important issues associated with this passive and auto sustainable acid mine drainage remediation method were investigated: 1) the potential use of alkaline clay as an AMD remediation material, 2) the adequate alkaline clay/coal refuse mixing ratio (AC/CR) to ensure pH values near to neutral conditions, and, 3) the prediction of long term impacts, in terms of the trends of the main parameters involved in this process such as pH, concentrations of sulfate, iron and other dissolved contaminants. Both field measurements and the samples used for the experiments came from a coal waste site located in Mather, Pennsylvania. Alkaline clay proved to be an effective remediation material for AMD. It was found that 10% AC/CR is an adequate mixing ratio (i.e. the upper limit), which has been also indicated by field measurements. The concentrations of some contaminants such as iron, manganese or sulfate are significantly reduced with the remediation approach, compared to those representative concentrations found in mine tailings. Moreover, results suggest a very reliable long-term stability of the remediation (i.e. neutral pH conditions are maintained), thus enhancing the generation of iron precipitates that could produce pyrite grain coating and hardpan (i.e. cemented layer) on the surface. These processes also made the amended layer less porous, thus increasing water retention and hindering oxygen diffusion.

  12. Metabolic Profile as a Potential Modifier of Long-Term Radiation Effects on Peripheral Lymphocyte Subsets in Atomic Bomb Survivors.

    PubMed

    Yoshida, Kengo; Nakashima, Eiji; Kyoizumi, Seishi; Hakoda, Masayuki; Hayashi, Tomonori; Hida, Ayumi; Ohishi, Waka; Kusunoki, Yoichiro

    2016-09-01

    Immune system impairments reflected by the composition and function of circulating lymphocytes are still observed in atomic bomb survivors, and metabolic abnormalities including altered blood triglyceride and cholesterol levels have also been detected in such survivors. Based on closely related features of immune and metabolic profiles of individuals, we investigated the hypothesis that long-term effects of radiation exposure on lymphocyte subsets might be modified by metabolic profiles in 3,113 atomic bomb survivors who participated in health examinations at the Radiation Effect Research Foundation, Hiroshima and Nagasaki, in 2000-2002. The lymphocyte subsets analyzed involved T-, B- and NK-cell subsets, and their percentages in the lymphocyte fraction were assessed using flow cytometry. Health examinations included metabolic indicators, body mass index, serum levels of total cholesterol, high-density lipoprotein cholesterol, C-reactive protein and hemoglobin A1c, as well as diabetes and fatty liver diagnoses. Standard regression analyses indicated that several metabolic indicators of obesity/related disease, particularly high-density lipoprotein cholesterol levels, were positively associated with type-1 helper T- and B-cell percentages but were inversely associated with naïve CD4 T and NK cells. A regression analysis adjusted for high-density lipoprotein cholesterol revealed a radiation dose relationship with increasing NK-cell percentage. Additionally, an interaction effect was suggested between radiation dose and C-reactive protein on B-cell percentage with a negative coefficient of the interaction term. Collectively, these findings suggest that radiation exposure and subsequent metabolic profile changes, potentially in relationship to obesity-related inflammation, lead to such long-term alterations in lymphocyte subset composition. Because this study is based on cross-sectional and exploratory analyses, the implications regarding radiation exposure, metabolic

  13. Requirement of rapid Ca2+ entry and synaptic activation of metabotropic glutamate receptors for the induction of long-term depression in adult rat hippocampus.

    PubMed

    Otani, S; Connor, J A

    1998-09-15

    1. During block of gamma-aminobutyric acid-A-mediated inhibition, low-frequency stimulation (2 Hz, 900 pulses) to Schaffer collateral-CA1 neuron synapses of adult rat hippocampus induced an N-methyl-D-aspartate receptor-independent, postsynaptic Ca2+-dependent depression of synaptic strength (long-term depression; LTD). 2. Ratio imaging with fura-2 revealed moderate dendritic [Ca2+] increases (approximately 500 nM) during only the initial approximately 30 s of the 7.5 min stimulation period. Conditioning for 30 s was, however, insufficient to induce LTD. 3. The [Ca2+] changes were insensitive to the metabotropic glutamate receptor (mGluR) antagonist (+)-alpha-methyl-4-carboxyphenylglycine (MCPG). MCPG, however, completely blocked LTD when present during conditioning. 4. The [Ca2+] changes were abolished by postsynaptic hyperpolarization (-110 mV at the soma). Hyperpolarizing neurons to -110 mV during conditioning significantly attenuated LTD induction. 5. LTD induction was also blocked by the postsynaptic presence of the protein kinase C inhibitor peptide PKC(19-36). 6. These results suggest that LTD induction in adult hippocampus by prolonged low-frequency stimulation depends on both a rapid Ca2+ influx through voltage-sensitive channels and synaptic stimulation of mGluRs which may be coupled to phospholipase C.

  14. Synergistic action of GABA-A and NMDA receptors in the induction of long-term depression in glutamatergic synapses in the newborn rat hippocampus.

    PubMed

    Pavlov, Ivan; Riekki, Ruusu; Taira, Tomi

    2004-12-01

    We show that activation of GABA(A) receptors (GABA(A)Rs) promotes induction of N-methyl-D-aspartate (NMDA) receptor (NMDAR)-dependent long-term depression (LTD) of glutamatergic synapses in the newborn rat hippocampal area CA1 in a developmentally restricted manner. In the newborn rat hippocampus two mechanistically different types of LTD of glutamatergic synapses could be induced under similar experimental conditions. The form of the LTD induced depended on the stimulation protocol and on the age of the animal. Low-frequency stimulation (1 Hz) with 100 stimuli induced a robust homosynaptic, reversible LTD at postnatal days 2-8 (P2-P8) but not at P14. This LTD was blocked by the NMDAR antagonist AP5 or by the GABA(A)R antagonist picrotoxin. Use of a low-chloride solution in the patch pipette resulting in E(GABA-A) < -70 mV blocked the NMDAR-dependent LTD, whereas clamping the cell to -40 mV during induction rescued it. In addition, it was possible to induce LTD at P14 with 100 stimuli if the cells were clamped to -40 mV during induction. Low-frequency stimulation with 900 stimuli induced a robust homosynaptic, reversible LTD both at P2-P8 and at P14. However, neither AP5 nor picrotoxin affected the LTD induced by 900 pulses at P2-P8. Instead, the 900 stimuli-induced LTD was blocked by the metabotropic glutamate receptor antagonists when co-applied with AP5. We suggest that during the first postnatal week postsynaptic depolarization provided by the activation of GABA(A)Rs shifts the threshold for the LTD induction, making the synapses more prone to activity-induced plasticity. From the second postnatal week onwards, when the GABA(A) responses are already hyperpolarizing, different mechanisms for LTD induction prevail. PMID:15579156

  15. Synergistic action of GABA-A and NMDA receptors in the induction of long-term depression in glutamatergic synapses in the newborn rat hippocampus.

    PubMed

    Pavlov, Ivan; Riekki, Ruusu; Taira, Tomi

    2004-12-01

    We show that activation of GABA(A) receptors (GABA(A)Rs) promotes induction of N-methyl-D-aspartate (NMDA) receptor (NMDAR)-dependent long-term depression (LTD) of glutamatergic synapses in the newborn rat hippocampal area CA1 in a developmentally restricted manner. In the newborn rat hippocampus two mechanistically different types of LTD of glutamatergic synapses could be induced under similar experimental conditions. The form of the LTD induced depended on the stimulation protocol and on the age of the animal. Low-frequency stimulation (1 Hz) with 100 stimuli induced a robust homosynaptic, reversible LTD at postnatal days 2-8 (P2-P8) but not at P14. This LTD was blocked by the NMDAR antagonist AP5 or by the GABA(A)R antagonist picrotoxin. Use of a low-chloride solution in the patch pipette resulting in E(GABA-A) < -70 mV blocked the NMDAR-dependent LTD, whereas clamping the cell to -40 mV during induction rescued it. In addition, it was possible to induce LTD at P14 with 100 stimuli if the cells were clamped to -40 mV during induction. Low-frequency stimulation with 900 stimuli induced a robust homosynaptic, reversible LTD both at P2-P8 and at P14. However, neither AP5 nor picrotoxin affected the LTD induced by 900 pulses at P2-P8. Instead, the 900 stimuli-induced LTD was blocked by the metabotropic glutamate receptor antagonists when co-applied with AP5. We suggest that during the first postnatal week postsynaptic depolarization provided by the activation of GABA(A)Rs shifts the threshold for the LTD induction, making the synapses more prone to activity-induced plasticity. From the second postnatal week onwards, when the GABA(A) responses are already hyperpolarizing, different mechanisms for LTD induction prevail.

  16. EGCG ameliorates the suppression of long-term potentiation induced by ischemia at the Schaffer collateral-CA1 synapse in the rat.

    PubMed

    Ding, Jie; Fu, Gang; Zhao, Yan; Cheng, Zhenyong; Chen, Yang; Zhao, Bo; He, Wei; Guo, Lian-Jun

    2012-03-01

    The function of Epigallocatechin gallate (EGCG), a main component of green tea, has been widely investigated, amelioration of synaptic transmission and neuroprotective effects against ischemia-induced brain damage among others. However, the mechanism underlying is still unveiled. We investigated the effects of EGCG on high frequency stimulation-induced long-term potentiation (LTP) in the Schaffer collateral-CA1 synapse with or without cerebral ischemia injury induced by middle cerebral artery occlusion (MCAO) in vivo to examine the possible relations between EGCG and synaptic transmission. Application of EGCG modulated synaptic transmission and produced a dose-dependent improvement of the induction of LTP. However, relative high-dose EGCG can block the induction of LTP at the Schaffer collateral-CA1 synapse in normal rat in vivo. In addition, the effects of EGCG were observed on the infarct volume and neurological deficit in rats subjected to MCAO; furthermore, the cell viability of primary cultured rat hippocampal and cortical neurons suffered from oxygen-glucose deprivation were evaluated with MTT and LDH assay, which showed significant neuroprotective properties in vitro. Surprisingly, the contents of the glutamate (Glu), glycine (Gly), and gamma-aminobutyric acid amino acids were totally disequilibrated before and after cerebral ischemia injury and could be rebalanced to original level by application of EGCG. Our results suggest that EGCG is able to improve the efficiency of synaptic transmission in cerebral ischemia injury with attenuated effect related to the neuroprotection of EGCG through regulating excitatory and inhibitory amino acid balance.

  17. Myosin II ATPase activity mediates the long-term potentiation-induced exodus of stable F-actin bound by drebrin A from dendritic spines.

    PubMed

    Mizui, Toshiyuki; Sekino, Yuko; Yamazaki, Hiroyuki; Ishizuka, Yuta; Takahashi, Hideto; Kojima, Nobuhiko; Kojima, Masami; Shirao, Tomoaki

    2014-01-01

    The neuronal actin-binding protein drebrin A forms a stable structure with F-actin in dendritic spines. NMDA receptor activation causes an exodus of F-actin bound by drebrin A (DA-actin) from dendritic spines, suggesting a pivotal role for DA-actin exodus in synaptic plasticity. We quantitatively assessed the extent of DA-actin localization to spines using the spine-dendrite ratio of drebrin A in cultured hippocampal neurons, and found that (1) chemical long-term potentiation (LTP) stimulation induces rapid DA-actin exodus and subsequent DA-actin re-entry in dendritic spines, (2) Ca(2+) influx through NMDA receptors regulates the exodus and the basal accumulation of DA-actin, and (3) the DA-actin exodus is blocked by myosin II ATPase inhibitor, but is not blocked by myosin light chain kinase (MLCK) or Rho-associated kinase (ROCK) inhibitors. These results indicate that myosin II mediates the interaction between NMDA receptor activation and DA-actin exodus in LTP induction. Furthermore, myosin II seems to be activated by a rapid actin-linked mechanism rather than slow MLC phosphorylation. Thus the myosin-II mediated DA-actin exodus might be an initial event in LTP induction, triggering actin polymerization and spine enlargement.

  18. Myosin II ATPase Activity Mediates the Long-Term Potentiation-Induced Exodus of Stable F-Actin Bound by Drebrin A from Dendritic Spines

    PubMed Central

    Mizui, Toshiyuki; Sekino, Yuko; Yamazaki, Hiroyuki; Ishizuka, Yuta; Takahashi, Hideto; Kojima, Nobuhiko; Kojima, Masami; Shirao, Tomoaki

    2014-01-01

    The neuronal actin-binding protein drebrin A forms a stable structure with F-actin in dendritic spines. NMDA receptor activation causes an exodus of F-actin bound by drebrin A (DA-actin) from dendritic spines, suggesting a pivotal role for DA-actin exodus in synaptic plasticity. We quantitatively assessed the extent of DA-actin localization to spines using the spine-dendrite ratio of drebrin A in cultured hippocampal neurons, and found that (1) chemical long-term potentiation (LTP) stimulation induces rapid DA-actin exodus and subsequent DA-actin re-entry in dendritic spines, (2) Ca2+ influx through NMDA receptors regulates the exodus and the basal accumulation of DA-actin, and (3) the DA-actin exodus is blocked by myosin II ATPase inhibitor, but is not blocked by myosin light chain kinase (MLCK) or Rho-associated kinase (ROCK) inhibitors. These results indicate that myosin II mediates the interaction between NMDA receptor activation and DA-actin exodus in LTP induction. Furthermore, myosin II seems to be activated by a rapid actin-linked mechanism rather than slow MLC phosphorylation. Thus the myosin-II mediated DA-actin exodus might be an initial event in LTP induction, triggering actin polymerization and spine enlargement. PMID:24465547

  19. Long-Term Care

    MedlinePlus

    ... this page please turn Javascript on. Long-Term Care What Is Long-Term Care? Long-term care involves a variety of services ... the Escape (Esc) button on your keyboard.) Most Care Provided at Home Long-term care is provided ...

  20. Long-Term Expansion, Enhanced Chondrogenic Potential, and Suppression of Endochondral Ossification of Adult Human MSCs via WNT Signaling Modulation

    PubMed Central

    Narcisi, Roberto; Cleary, Mairéad A.; Brama, Pieter A.J.; Hoogduijn, Martin J.; Tüysüz, Nesrin; ten Berge, Derk; van Osch, Gerjo J.V.M.

    2015-01-01

    Summary Mesenchymal stem cells (MSCs) are a potential source of chondrogenic cells for the treatment of cartilage disorders, but loss of chondrogenic potential during in vitro expansion and the propensity of cartilage to undergo hypertrophic maturation impede their therapeutic application. Here we report that the signaling protein WNT3A, in combination with FGF2, supports long-term expansion of human bone marrow-derived MSCs. The cells retained their chondrogenic potential and other phenotypic and functional properties of multipotent MSCs, which were gradually lost in the absence of WNT3A. Moreover, we discovered that endogenous WNT signals are the main drivers of the hypertrophic maturation that follows chondrogenic differentiation. Inhibition of WNT signals during differentiation prevented calcification and maintained cartilage properties following implantation in a mouse model. By maintaining potency during expansion and preventing hypertrophic maturation following differentiation, the modulation of WNT signaling removes two major obstacles that impede the clinical application of MSCs in cartilage repair. PMID:25733021

  1. Effects of 4-weeks of treatment with lithium and olanzapine on long-term potentiation in hippocampal area CA1.

    PubMed

    Shim, Seong S; Hammonds, Michael D; Tatsuoka, Curtis; Feng, I Jung

    2012-08-22

    Neuroplastic theories propose that lithium has robust neuroprotective and neurotrophic actions leading to the up-regulation of synaptic plasticity, and this action may be associated with the efficacy of lithium in the treatment of bipolar disorder. Olanzapine, an atypical antipsychotic drug, is efficacious in the treatment of bipolar disorder. It has been suggested that olanzapine may also up-regulate synaptic plasticity by its neuroprotective and neurotrophic actions, and this action may be related to antipsychotic and anti-manic effects of the drug. However, few studies have directly examined whether these drugs alter synaptic plasticity. In the present study, to examine the effects of lithium and olanzapine on synaptic plasticity, we examined the effects of chronic treatment with lithium and olanzapine on long-term potentiation (LTP) and input and output (I/O) responses of field excitatory postsynaptic potentials (fEPSP) of CA1 pyramidal cells in hippocampal slices prepared from rats administered the drugs for 4 weeks. Our results show that 4 weeks of lithium treatment magnified LTP of CA1 pyramidal cells. However, the same treatment with olanzapine did not magnify LTP of CA1 pyramidal cells. Four weeks of treatment with lithium did not alter I/O responses of CA1 pyramidal cells. However, the same treatment with olanzapine increased I/O responses of CA1 pyramidal cells. The results suggest that lithium up-regulates synaptic plasticity in the hippocampus, and olanzapine increases synaptic transmission without apparent changes in LTP in the hippocampus.

  2. Ethanol Blocks Long-Term Potentiation of GABAergic Synapses in the Ventral Tegmental Area Involving μ-Opioid Receptors

    PubMed Central

    Guan, Yan-zhong; Ye, Jiang-Hong

    2010-01-01

    It is well documented that ethanol exposure alters GABA (γ-aminobutyric acid)-releasing synapses, and ethanol addiction is associated with endogenous opioid system. Emerging evidence indicates that opioids block long-term potentiation in the fast inhibitory GABAA receptor synapses (LTPGABA) onto dopamine-containing neurons in the ventral tegmental area (VTA), a brain region essential for reward-seeking behavior. However, how ethanol affects LTPGABA is not known. We report here that in acute midbrain slices from rats, clinically relevant concentrations of ethanol applied both in vitro and in vivo prevents LTPGABA, which is reversed, respectively, by in vitro and in vivo administration of naloxone, a μ-opioid receptor (MOR) antagonist. Furthermore, the blockade of LTPGABA induced by a brief in vitro ethanol treatment is mimicked by DAMGO ([-Ala2, N-MePhe4, Gly-ol]-enkephalin), a MOR agonist. Paired-pulse ratios are similar in slices, 24 h after in vivo injection with either saline or ethanol. Sp-cAMPS, a stable cAMP analog, and pCPT-cGMP, a cGMP analog, potentiates GABAA-mediated inhibitory postsynaptic currents in slices from ethanol-treated rats, indicating that a single in vivo ethanol exposure does not maximally increase GABA release, instead, ethanol produces a long-lasting inability to generate LTPGABA. These neuroadaptations to ethanol might contribute to early stage of addiction. PMID:20393452

  3. Effects of memantine on hippocampal long-term potentiation, gamma activity, and sensorimotor gating in freely moving rats.

    PubMed

    Ma, Jingyi; Mufti, Asfandyar; Stan Leung, L

    2015-09-01

    Memantine, an uncompetitive N-methyl-D-aspartate receptor antagonist, is used for treatment of patients with Alzheimer's disease. The mechanisms of memantine in relieving cognitive and behavioral symptoms are unclear, and this study attempts to elucidate its action on network and synaptic functions of the hippocampus. The effects of memantine on electrographic activity and hippocampal long-term potentiation (LTP) were investigated in freely moving rats. Basal dendritic excitation on hippocampal CA1 pyramidal cells showed a robust LTP after theta-frequency primed bursts, and the LTP was higher after 5-10 mg/kg intraperitoneal (ip) memantine pretreatment, as compared with saline pretreatment. Injection of scopolamine (5 mg/kg ip) before memantine failed to block the LTP-enhancing effect of memantine. Memantine as compared with saline pretreatment did not affect the LTP after an afterdischarge induced by high-frequency (200-Hz) train stimulation. Memantine (5 or 10 mg/kg ip) significantly enhanced gamma oscillations in the hippocampal local field potentials of 40-100 Hz during walking and awake immobility. Memantine at 10 mg/kg ip, but not at 5 mg/kg ip, increased prepulse inhibition of the acoustic startle response, while both 5 and 10 mg/kg ip memantine enhanced the acoustic startle response as compared with saline-injected rats. These electrophysiological and behavioral effects of memantine are unique among N-methyl-D-aspartate receptor antagonists but are consistent with memantine's effects in improving cognitive and sensorimotor functions of Alzheimer's patients.

  4. Mutant mice deficient in NOS-1 exhibit attenuated long-term facilitation and short-term potentiation in breathing

    PubMed Central

    Kline, David D; Overholt, Jeffery L; Prabhakar, Nanduri R

    2002-01-01

    The objective of the present study is to examine the potential role of nitric oxide (NO) in short-term potentiation (STP) and long-term facilitation (LTF) of breathing. Experiments were performed in wild-type (WT) and mutant mice deficient in nitric oxide synthase-1 (NOS-1), as well as in WT mice administered the NOS-1 inhibitor 7-nitroindazole (7-NI; 50 mg kg−1; i.p.). Respiratory responses following either single or recurrent episodes of hypoxia (7 % O2, balance N2) were analysed in unanaesthetised animals by body plethysmography along with rate of O2 consumption (V̇O2) and CO2 production (V̇CO2). After a single hypoxic challenge, respiration in WT mice remained elevated for 5 min, suggesting STP in ventilation. Following termination of three consecutive hypoxic challenges, respiration remained elevated during normoxia for as long as 30 min, indicating LTF in breathing under awake conditions. STP and LTF were significantly attenuated or absent in WT mice after 7-NI. A similar attenuation or absence of STP and LTF was also seen in NOS-1 mutant mice. Changes in V̇O2 and V̇CO2 were comparable among mice during the post-hypoxic period, suggesting that the absence of STP and LTF was not due to alterations in body metabolism. These results suggest endogenous NO is an important physiological modulator of ventilatory STP and LTF. PMID:11850522

  5. X11β rescues memory and long-term potentiation deficits in Alzheimer's disease APPswe Tg2576 mice

    PubMed Central

    Mitchell, Jacqueline C.; Ariff, Belall B.; Yates, Darran M.; Lau, Kwok-Fai; Perkinton, Michael S.; Rogelj, Boris; Stephenson, John D.; Miller, Christopher C.J.; McLoughlin, Declan M.

    2009-01-01

    Increased production and deposition of amyloid β-protein (Aβ) are believed to be key pathogenic events in Alzheimer's disease. As such, routes for lowering cerebral Aβ levels represent potential therapeutic targets for Alzheimer's disease. X11β is a neuronal adaptor protein that binds to the intracellular domain of the amyloid precursor protein (APP). Overexpression of X11β inhibits Aβ production in a number of experimental systems. However, whether these changes to APP processing and Aβ production induced by X11β overexpression also induce beneficial effects to memory and synaptic plasticity are not known. We report here that X11β-mediated reduction in cerebral Aβ is associated with normalization of both cognition and in vivo long-term potentiation in aged APPswe Tg2576 transgenic mice that model the amyloid pathology of Alzheimer's disease. Overexpression of X11β itself has no detectable adverse effects upon mouse behaviour. These findings support the notion that modulation of X11β function represents a therapeutic target for Aβ-mediated neuronal dysfunction in Alzheimer's disease. PMID:19744962

  6. Long-term follow-up of patients with diffuse large B-cell non-Hodgkin’s lymphoma receiving purged autografts after induction failure

    PubMed Central

    Benjamin, JE; Chen, GL; Cao, TM; Cao, PD; Wong, RM; Sheehan, K; Shizuru, JA; Johnston, LJ; Negrin, RS; Lowsky, R; Laport, GG

    2010-01-01

    Patients with diffuse large B-cell lymphoma (DLBCL) who do not achieve a complete response to front-line combination chemotherapy are often offered high-dose therapy and autologous hematopoietic cell transplantation (AHCT). However, the efficacy of this therapy in this patient population has been addressed in only a few published reports. We retrospectively analyzed the outcomes of patients with a diagnosis of de novo DLBCL who underwent AHCT at our center between 1988 and 2002, and identified 43 consecutive patients who had not achieved a CR before AHCT, although most showed at least a partial response (PR) to either induction or subsequent salvage chemotherapy. A total of 15 patients received a conditioning regimen that included high-dose chemotherapy with fractionated TBI (FTBI), whereas 28 patients received high-dose chemotherapy only. All autografts were treated ex vivo with MoAbs and complement in an effort to remove any residual malignant B cells. A total of 33 (77%) patients achieved a CR after AHCT. With a median follow-up of 7.3 years, the 5-year OS was 69% and EFS was 59%. Four patients died from non-relapse mortality. By univariate analyses, the following characteristics did not significantly impact OS: disease stage at diagnosis, age-adjusted IPI (International Prognostic Index) score, age ≥40 years, earlier radiotherapy and the use of FTBI in the conditioning regimen. These results confirm the long-term efficacy of AHCT for patients with DLBCL after induction failure. PMID:19597427

  7. Presynaptic long-term plasticity

    PubMed Central

    Yang, Ying; Calakos, Nicole

    2013-01-01

    Long-term synaptic plasticity is a major cellular substrate for learning, memory, and behavioral adaptation. Although early examples of long-term synaptic plasticity described a mechanism by which postsynaptic signal transduction was potentiated, it is now apparent that there is a vast array of mechanisms for long-term synaptic plasticity that involve modifications to either or both the presynaptic terminal and postsynaptic site. In this article, we discuss current and evolving approaches to identify presynaptic mechanisms as well as discuss their limitations. We next provide examples of the diverse circuits in which presynaptic forms of long-term synaptic plasticity have been described and discuss the potential contribution this form of plasticity might add to circuit function. Finally, we examine the present evidence for the molecular pathways and cellular events underlying presynaptic long-term synaptic plasticity. PMID:24146648

  8. D-cycloserine prevents relational memory deficits and suppression of long-term potentiation induced by scopolamine in the hippocampus.

    PubMed

    Portero-Tresserra, Marta; Del Olmo, Nuria; Martí-Nicolovius, Margarita; Guillazo-Blanch, Gemma; Vale-Martínez, Anna

    2014-11-01

    Previous research has demonstrated that systemic D-cycloserine (DCS), a partial agonist of the N-methyl-D-aspartate receptor (NMDAR), enhances memory processes in different learning paradigms and attenuates mnemonic deficits produced by diverse pharmacological manipulations. In the present study two experiments were conducted in rats to investigate whether DCS administered in the hippocampus may rescue relational memory deficits and improve deficient synaptic plasticity, both induced by an intracerebral injection of the muscarinic receptor antagonist scopolamine (SCOP). In experiment 1, we assessed whether DCS would prevent SCOP-induced amnesia in an olfactory learning paradigm requiring the integrity of the cholinergic system, the social transmission of food preference (STFP). The results showed that DCS (10 μg/site) injected into the ventral hippocampus (vHPC) before STFP acquisition compensated the 24-h retention deficit elicited by post-training intra-vHPC SCOP (40 μg/site), although it did not affect memory expression in non-SCOP treated rats. In experiment 2, we evaluated whether the perfusion of DCS in hippocampal slices may potentiate synaptic plasticity in CA1 synapses and thus recover SCOP-induced deficits in long-term potentiation (LTP). We found that DCS (50 µM and 100 µM) was able to rescue SCOP (100 µM)-induced LTP maintenance impairment, in agreement with the behavioral findings. Additionally, DCS alone (50 µM and 100 µM) enhanced field excitatory postsynaptic potentials prior to high frequency stimulation, although it did not significantly potentiate LTP. Our results suggest that positive modulation of the NMDAR, by activation of the glycine-binding site, may compensate relational memory impairments due to hippocampal muscarinic neurotransmission dysfunction possibly through enhancements in LTP maintenance.

  9. Heterosynaptic long-term potentiation at interneuron-principal neuron synapses in the amygdala requires nitric oxide signalling.

    PubMed

    Lange, M D; Doengi, M; Lesting, J; Pape, H C; Jüngling, K

    2012-01-01

    Long-lasting changes of synaptic efficacy are thought to be a prerequisite for memory formation and maintenance. In the basolateral complex of the amygdala (BLA), one of the main regions for fear and extinction learning of the brain, various forms of long-term potentiation (LTP) have been described for excitatory glutamatergic synapses. In contrast, little is known about the mechanisms of LTP at inhibitory GABAergic synapses. Here we provide evidence that (1) LTP at inhibitory GABAergic synapses (LTP(i)) between inhibitory interneurons and principal neurons (PNs) can be induced by theta-burst stimulation (TBS), (2) this LTP(i) is prevented by AMPA- or NMDA-receptor antagonists, and (3) this LTP(i) is abolished by the NO synthase (NOS) inhibitor L-NAME or the NO scavenger PTIO, and thus is critically dependent on nitric oxide (NO) signalling. These findings are corroborated by immunocytochemical stainings for neuronal (n) NOS, which revealed the existence of nNOS-positive neurons and fibres in the BLA. We conclude that LTP of GABAergic synaptic transmission to PNs is induced by activation of AMPA and NMDA receptors at glutamatergic synapses and subsequent retrograde NO signalling to enhance GABAergic transmission. This form of LTP at GABAergic synapses comprises a novel form of heterosynaptic plasticity within the BLA, apt to shape conditioned fear responses. PMID:22041183

  10. Long-term in vitro maintenance of clonal abundance and leukaemia-initiating potential in acute lymphoblastic leukaemia

    PubMed Central

    Pal, D; Blair, H J; Elder, A; Dormon, K; Rennie, K J; Coleman, D J L; Weiland, J; Rankin, K S; Filby, A; Heidenreich, O; Vormoor, J

    2016-01-01

    Lack of suitable in vitro culture conditions for primary acute lymphoblastic leukaemia (ALL) cells severely impairs their experimental accessibility and the testing of new drugs on cell material reflecting clonal heterogeneity in patients. We show that Nestin-positive human mesenchymal stem cells (MSCs) support expansion of a range of biologically and clinically distinct patient-derived ALL samples. Adherent ALL cells showed an increased accumulation in the S phase of the cell cycle and diminished apoptosis when compared with cells in the suspension fraction. Moreover, surface expression of adhesion molecules CD34, CDH2 and CD10 increased several fold. Approximately 20% of the ALL cells were in G0 phase of the cell cycle, suggesting that MSCs may support quiescent ALL cells. Cellular barcoding demonstrated long-term preservation of clonal abundance. Expansion of ALL cells for >3 months compromised neither feeder dependence nor cancer initiating ability as judged by their engraftment potential in immunocompromised mice. Finally, we demonstrate the suitability of this co-culture approach for the investigation of drug combinations with luciferase-expressing primograft ALL cells. Taken together, we have developed a preclinical platform with patient-derived material that will facilitate the development of clinically effective combination therapies for ALL. PMID:27109511

  11. Chronic fluoxetine treatment induces brain region-specific upregulation of genes associated with BDNF-induced long-term potentiation.

    PubMed

    Alme, Maria Nordheim; Wibrand, Karin; Dagestad, Grethe; Bramham, Clive R

    2007-01-01

    Several lines of evidence implicate BDNF in the pathogenesis of stress-induced depression and the delayed efficacy of antidepressant drugs. Antidepressant-induced upregulation of BDNF signaling is thought to promote adaptive neuronal plasticity through effects on gene expression, but the effector genes downstream of BDNF has not been identified. Local infusion of BDNF into the dentate gyrus induces a long-term potentiation (BDNF-LTP) of synaptic transmission that requires upregulation of the immediate early gene Arc. Recently, we identified five genes (neuritin, Narp, TIEG1, Carp, and Arl4d) that are coupregulated with Arc during BDNF-LTP. Here, we examined the expression of these genes in the dentate gyrus, hippocampus proper, and prefrontal cortex after antidepressant treatment. We show that chronic, but not acute, fluoxetine administration leads to upregulation of these BDNF-LTP-associated genes in a brain region-specific pattern. These findings link chronic effects of antidepressant treatment to molecular mechanisms underlying BDNF-induced synaptic plasticity. PMID:18301726

  12. Enhanced Deficits in Long-Term Potentiation in the Adult Dentate Gyrus with 2nd Trimester Ethanol Consumption

    PubMed Central

    Helfer, Jennifer L.; White, Emily R.; Christie, Brian R.

    2012-01-01

    Ethanol exposure during pregnancy can cause structural and functional changes in the brain that can impair cognitive capacity. The hippocampal formation, an area of the brain strongly linked with learning and memory, is particularly vulnerable to the teratogenic effects of ethanol. In the present experiments we sought to determine if the functional effects of developmental ethanol exposure could be linked to ethanol exposure during any single trimester-equivalent. Ethanol exposure during the 1st or 3rd trimester-equivalent produced only minor changes in synaptic plasticity in adult offspring. In contrast, ethanol exposure during the 2nd trimester equivalent resulted in a pronounced decrease in long-term potentiation, indicating that the timing of exposure influences the severity of the deficit. Together, the results from these experiments demonstrate long-lasting alterations in synaptic plasticity as the result of developmental ethanol exposure and dependent on the timing of exposure. Furthermore, these results allude to neural circuit malfunction within the hippocampal formation, perhaps relating to the learning and memory deficits observed in individuals with fetal alcohol spectrum disorders. PMID:23227262

  13. Despair-associated memory requires a slow-onset CA1 long-term potentiation with unique underlying mechanisms.

    PubMed

    Jing, Liang; Duan, Ting-Ting; Tian, Meng; Yuan, Qiang; Tan, Ji-Wei; Zhu, Yong-Yong; Ding, Ze-Yang; Cao, Jun; Yang, Yue-Xiong; Zhang, Xia; Mao, Rong-Rong; Richter-Levin, Gal; Zhou, Qi-Xin; Xu, Lin

    2015-01-01

    The emotion of despair that occurs with uncontrollable stressful event is probably retained by memory, termed despair-associated memory, although little is known about the underlying mechanisms. Here, we report that forced swimming (FS) with no hope to escape, but not hopefully escapable swimming (ES), enhances hippocampal α-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR)-dependent GluA1 Ser831 phosphorylation (S831-P), induces a slow-onset CA1 long-term potentiation (LTP) in freely moving rats and leads to increased test immobility 24-h later. Before FS application of the antagonists to block S831-P or N-methyl-D-aspartic acid receptor (NMDAR) or glucocorticoid receptor (GR) disrupts LTP and reduces test immobility, to levels similar to those of the ES group. Because these mechanisms are specifically linked with the hopeless of escape from FS, we suggest that despair-associated memory occurs with an endogenous CA1 LTP that is intriguingly mediated by a unique combination of rapid S831-P with NMDAR and GR activation to shape subsequent behavioral despair. PMID:26449319

  14. In-Situ Strain Analysis of Potential Habitat Composites Exposed to a Simulated Long-Term Lunar Radiation Exposure

    NASA Technical Reports Server (NTRS)

    Rojdev, Kristina; O'Rourke, Mary Jane; Hill, Charles; Nutt, Steven; Atwell, William

    2010-01-01

    NASA is studying the effects of long-term space radiation on potential multifunctional composite materials for habitats to better determine their characteristics in the harsh space environment. Two composite materials were selected for the study and were placed in a test stand that simulated the stresses of a pressure vessel wall on the material. The samples in the test stand were exposed to radiation at either a fast dose rate or a slow dose rate, and their strain and temperature was recorded during the exposure. It was found that during a fast dose rate exposure the materials saw a decreased strain with time, or a shrinking of the materials. Given previous radiation studies of polymers, this is believed to be a result of crosslinking occurring in the matrix material. However, with a slow dose rate, the materials saw an increase in strain with time, or a stretching of the materials. This result is consistent with scission or degradation of the matrix occurring, possibly due to oxidative degradation.

  15. DCP-LA neutralizes mutant amyloid beta peptide-induced impairment of long-term potentiation and spatial learning.

    PubMed

    Nagata, Tetsu; Tomiyama, Takami; Tominaga, Takemi; Mori, Hiroshi; Yaguchi, Takahiro; Nishizaki, Tomoyuki

    2010-01-01

    Long-term potentiation (LTP) was monitored from the CA1 region of the intact rat hippocampus by delivering high frequency stimulation (HFS) to the Schaffer collateral commissural pathway. Intraventricular injection with mutant amyloid beta(1-42) peptide lacking glutamate-22 (Abeta(1-42)E22Delta), favoring oligomerization, 10 min prior to HFS, inhibited expression of LTP, with the potency more than wild-type amyloid beta(1-42) peptide. Intraperitoneal injection with the linoleic acid derivative 8-[2-(2-pentyl-cyclopropylmethyl)-cyclopropyl]-octanoic acid (DCP-LA) 70 min prior to HFS neutralized mutant Abeta(1-42)E22Delta peptide-induced LTP inhibition. In the water maze test, continuous intraventricular injection with mutant Abeta(1-42)E22Delta peptide for 14 days prolonged the acquisition latency as compared with that for control, with the potency similar to wild-type Abeta(1-42) peptide, and intraperitoneal injection with DCP-LA shortened the prolonged latency to control levels. The results of the present study indicate that DCP-LA neutralizes mutant Abeta(1-42)E22Delta peptide-induced impairment of LTP and spatial learning.

  16. Long-term monitoring of airborne nickel (Ni) pollution in association with some potential source processes in the urban environment.

    PubMed

    Kim, Ki-Hyun; Shon, Zang-Ho; Mauulida, Puteri T; Song, Sang-Keun

    2014-09-01

    The environmental behavior and pollution status of nickel (Ni) were investigated in seven major cities in Korea over a 13-year time span (1998-2010). The mean concentrations of Ni measured during the whole study period fell within the range of 3.71 (Gwangju: GJ) to 12.6ngm(-3) (Incheon: IC). Although Ni values showed a good comparability in a relatively large spatial scale, its values in most cities (6 out of 7) were subject to moderate reductions over the study period. To assess the effect of major sources on the long-term distribution of Ni, the relationship between their concentrations and the potent source processes like non-road transportation sources (e.g., ship and aircraft emissions) were examined from some cities with port and airport facilities. The potential impact of long-range transport of Asian dust particles in controlling Ni levels was also evaluated. The overall results suggest that the Ni levels were subject to gradual reductions over the study period irrespective of changes in such localized non-road source activities. The pollution of Ni at all the study sites was maintained well below the international threshold (Directive 2004/107/EC) value of 20ngm(-3).

  17. Despair-associated memory requires a slow-onset CA1 long-term potentiation with unique underlying mechanisms

    PubMed Central

    Jing, Liang; Duan, Ting-Ting; Tian, Meng; Yuan, Qiang; Tan, Ji-Wei; Zhu, Yong-Yong; Ding, Ze-Yang; Cao, Jun; Yang, Yue-Xiong; Zhang, Xia; Mao, Rong-Rong; Richter-levin, Gal; Zhou, Qi-Xin; Xu, Lin

    2015-01-01

    The emotion of despair that occurs with uncontrollable stressful event is probably retained by memory, termed despair-associated memory, although little is known about the underlying mechanisms. Here, we report that forced swimming (FS) with no hope to escape, but not hopefully escapable swimming (ES), enhances hippocampal α-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR)-dependent GluA1 Ser831 phosphorylation (S831-P), induces a slow-onset CA1 long-term potentiation (LTP) in freely moving rats and leads to increased test immobility 24-h later. Before FS application of the antagonists to block S831-P or N-methyl-D-aspartic acid receptor (NMDAR) or glucocorticoid receptor (GR) disrupts LTP and reduces test immobility, to levels similar to those of the ES group. Because these mechanisms are specifically linked with the hopeless of escape from FS, we suggest that despair-associated memory occurs with an endogenous CA1 LTP that is intriguingly mediated by a unique combination of rapid S831-P with NMDAR and GR activation to shape subsequent behavioral despair. PMID:26449319

  18. Long-term quality of life after intensified multi-modality treatment of oral cancer including intra-arterial induction chemotherapy and adjuvant chemoradiation

    PubMed Central

    Kovács, Adorján F.; Stefenelli, Ulrich; Thorn, Gerrit

    2015-01-01

    Background: Quality of life (QoL) studies are well established when accompanying trials in head and neck cancer, but studies on long-term survivors are rare. Aims: The aim was to evaluate long-term follow-up patients treated with an intensified multi-modality therapy. Setting and Design: Cross-sectional study, tertiary care center. Patients and Methods: A total of 135 oral/oropharyngeal cancer survivors having been treated with an effective four modality treatment (intra-arterial induction chemotherapy, radical surgery, adjuvant radiation, concurrent systemic chemotherapy) filled European Organisation for Research and Treatment of Cancer (EORTC) QLQ-C30 and HN35 questionnaires. Mean distance to treatment was 6.1 (1.3–16.6) years. Results were compared with a reference patient population (EORTC reference manual). In-study group comparison was also carried out. Statistical Analysis: One-sample t-test, Mann–Whitney-test, Kruskal–Wallis analysis. Results: QoL scores of both populations were well comparable. Global health status, cognitive and social functioning, fatigue, social eating, status of teeth, mouth opening and dryness, and sticky saliva were significantly worse in the study population; pain and need for pain killers, cough, need for nutritional support, problems with weight loss and gain were judged to be significantly less. Patients 1-year posttreatment had generally worse scores as compared to patients with two or more years distance to treatment. Complex reconstructive measures and adjuvant (chemo) radiation were main reasons for significant impairment of QoL. Conclusion Subjective disease status of patients following a maximized multi-modality treatment showed an expectable high degree of limitations, but was generally comparable to a reference group treated less intensively, suggesting that the administration of an intensified multi-modality treatment is feasible in terms of QoL/effectivity ratio. PMID:26389030

  19. Wnt-5a prevents Aβ-induced deficits in long-term potentiation and spatial memory in rats.

    PubMed

    Zhang, Gui-Li; Zhang, Jun; Li, Shao-Feng; Lei, Liu; Xie, Hong-Yan; Deng, Fang; Feng, Jia-Chun; Qi, Jin-Shun

    2015-10-01

    Although the neurotoxicity of amyloid β (Aβ) protein in Alzheimer's disease (AD) has been reported widely, the exact molecular mechanism underlying the Aβ-induced synaptic dysfunction and memory impairment remains largely unclear. Growing evidence indicates that wingless-type (Wnt) signaling plays an important role in neuronal development, synapse formation and synaptic plasticity. In the present study, we investigated the neuroprotective action of Wnt-5a against the synaptic damage and memory deficit induced by Aβ25-35 by using in vivo electrophysiological recording and Morris water maze (MWM) test. We found that intracerebroventricular (i.c.v.) injection of Aβ25-35 alone did not affect the baseline field excitatory postsynaptic potentials (fEPSPs) and the paired-pulse facilitation (PPF) in the hippocampal CA1 region of rats, but significantly suppressed high frequency stimulation (HFS) induced long-term potentiation (LTP); pretreatment with Wnt-5a prevented the Aβ25-35-induced suppression of hippocampal LTP in a dose-dependent manner; soluble Frizzled-related protein (sFRP), a specific Wnt antagonist, effectively attenuated the protective effects of Wnt-5a. In MWM test, Aβ25-35 alone significantly disrupted spatial learning and memory ability of rats, while pretreatment with Wnt-5a effectively prevented the impairments induced by Aβ25-35. These results in the present study demonstrated for the first time the neuroprotective effects of Wnt-5a against Aβ-induced in vivo synaptic plasticity impairment and memory disorder, suggesting that Wnt signaling pathway is one of the important targets of Aβ neurotoxicity and Wnt-5a might be used as one of the putative candidates for the therapeutic intervention of AD.

  20. Regulation of Synaptic Rac1 Activity, Long-Term Potentiation Maintenance, and Learning and Memory by BCR and ABR Rac GTPase-Activating Proteins

    PubMed Central

    Oh, Daeyoung; Han, Seungnam; Seo, Jinsoo; Lee, Jae-Ran; Choi, Jeonghoon; Groffen, John; Kim, Karam; Cho, Yi Sul; Choi, Han-Saem; Shin, Hyewon; Woo, Jooyeon; Won, Hyejung; Park, Soon Kwon; Kim, Soo-Young; Jo, Jihoon; Whitcomb, Daniel J.; Cho, Kwangwook; Kim, Hyun; Bae, Yong Chul; Heisterkamp, Nora; Choi, Se-Young; Kim, Eunjoon

    2016-01-01

    Rho family small GTPases are important regulators of neuronal development. Defective Rho regulation causes nervous system dysfunctions including mental retardation and Alzheimer’s disease. Rac1, a member of the Rho family, regulates dendritic spines and excitatory synapses, but relatively little is known about how synaptic Rac1 is negatively regulated. Breakpoint cluster region (BCR) is a Rac GTPase-activating protein known to form a fusion protein with the c-Abl tyrosine kinase in Philadelphia chromosome-positive chronic myelogenous leukemia. Despite the fact that BCR mRNAs are abundantly expressed in the brain, the neural functions of BCR protein have remained obscure. We report here that BCR and its close relative active BCR-related (ABR) localize at excitatory synapses and directly interact with PSD-95, an abundant postsynaptic scaffolding protein. Mice deficient for BCR or ABR show enhanced basal Rac1 activity but only a small increase in spine density. Importantly, mice lacking BCR or ABR exhibit a marked decrease in the maintenance, but not induction, of long-term potentiation, and show impaired spatial and object recognition memory. These results suggest that BCR and ABR have novel roles in the regulation of synaptic Rac1 signaling, synaptic plasticity, and learning and memory, and that excessive Rac1 activity negatively affects synaptic and cognitive functions. PMID:20962234

  1. Inhibition of long-term potentiation in the schaffer-CA1 pathway by repetitive high-intensity sound stimulation.

    PubMed

    Cunha, A O S; de Oliveira, J A C; Almeida, S S; Garcia-Cairasco, N; Leão, R M

    2015-12-01

    High-intensity sound can induce seizures in susceptible animals. After repeated acoustic stimuli changes in behavioural seizure repertoire and epileptic EEG activity might be seen in recruited limbic and forebrain structures, a phenomenon known as audiogenic kindling. It is postulated that audiogenic kindling can produce synaptic plasticity events leading to the spread of epileptogenic activity to the limbic system. In order to test this hypothesis, we investigated if long-term potentiation (LTP) of hippocampal Schaffer-CA1 synapses and spatial navigation memory are altered by a repeated high-intensity sound stimulation (HISS) protocol, consisting of one-minute 120 dB broadband noise applied twice a day for 10 days, in normal Wistar rats and in audiogenic seizure-prone rats (Wistar Audiogenic Rats - WARs). After HISS all WARs exhibited midbrain seizures and 50% of these animals developed limbic recruitment, while only 26% of Wistar rats presented midbrain seizures and none of them had limbic recruitment. In naïve animals, LTP in hippocampal CA1 neurons was induced by 50- or 100-Hz high-frequency stimulation of Schaffer fibres in slices from both Wistar and WAR animals similarly. Surprisingly, HISS suppressed LTP in CA1 neurons in slices from Wistar rats that did not present any seizure, and inhibited LTP in slices from Wistar rats with only midbrain seizures. However HISS had no effect on LTP in CA1 neurons from slices of WARs. Interestingly HISS did not alter spatial navigation and memory in both strains. These findings show that repeated high-intensity sound stimulation prevent LTP of Schaffer-CA1 synapses from Wistar rats, without affecting spatial memory. This effect was not seen in hippocampi from audiogenic seizure-prone WARs. In WARs the link between auditory stimulation and hippocampal LTP seems to be disrupted which could be relevant for the susceptibility to seizures in this strain.

  2. Impaired spatial memory and enhanced long-term potentiation in mice with forebrain-specific ablation of the Stim genes.

    PubMed

    Garcia-Alvarez, Gisela; Shetty, Mahesh S; Lu, Bo; Yap, Kenrick An Fu; Oh-Hora, Masatsugu; Sajikumar, Sreedharan; Bichler, Zoë; Fivaz, Marc

    2015-01-01

    Recent findings point to a central role of the endoplasmic reticulum-resident STIM (Stromal Interaction Molecule) proteins in shaping the structure and function of excitatory synapses in the mammalian brain. The impact of the Stim genes on cognitive functions remains, however, poorly understood. To explore the function of the Stim genes in learning and memory, we generated three mouse strains with conditional deletion (cKO) of Stim1 and/or Stim2 in the forebrain. Stim1, Stim2, and double Stim1/Stim2 cKO mice show no obvious brain structural defects or locomotor impairment. Analysis of spatial reference memory in the Morris water maze revealed a mild learning delay in Stim1 cKO mice, while learning and memory in Stim2 cKO mice was indistinguishable from their control littermates. Deletion of both Stim genes in the forebrain resulted, however, in a pronounced impairment in spatial learning and memory reflecting a synergistic effect of the Stim genes on the underlying neural circuits. Notably, long-term potentiation (LTP) at CA3-CA1 hippocampal synapses was markedly enhanced in Stim1/Stim2 cKO mice and was associated with increased phosphorylation of the AMPA receptor subunit GluA1, the transcriptional regulator CREB and the L-type Voltage-dependent Ca(2+) channel Cav1.2 on protein kinase A (PKA) sites. We conclude that STIM1 and STIM2 are key regulators of PKA signaling and synaptic plasticity in neural circuits encoding spatial memory. Our findings also reveal an inverse correlation between LTP and spatial learning/memory and suggest that abnormal enhancement of cAMP/PKA signaling and synaptic efficacy disrupts the formation of new memories.

  3. Exposure to Kynurenic Acid during Adolescence Increases Sign-Tracking and Impairs Long-Term Potentiation in Adulthood

    PubMed Central

    DeAngeli, Nicole E.; Todd, Travis P.; Chang, Stephen E.; Yeh, Hermes H.; Yeh, Pamela W.; Bucci, David J.

    2015-01-01

    Changes in brain reward systems are thought to contribute significantly to the cognitive and behavioral impairments of schizophrenia, as well as the propensity to develop co-occurring substance abuse disorders. Presently, there are few treatments for persons with a dual diagnosis and little is known about the neural substrates that underlie co-occurring schizophrenia and substance abuse. One goal of the present study was to determine if a change in the concentration of kynurenic acid (KYNA), a tryptophan metabolite that is increased in the brains of people with schizophrenia, affects reward-related behavior. KYNA is an endogenous antagonist of NMDA glutamate receptors and α7 nicotinic acetylcholine receptors, both of which are critically involved in neurodevelopment, plasticity, and behavior. In Experiment 1, rats were treated throughout adolescence with L-kynurenine (L-KYN), the precursor of KYNA. As adults, the rats were tested drug-free in an autoshaping procedure in which a lever was paired with food. Rats treated with L-KYN during adolescence exhibited increased sign-tracking behavior (lever pressing) when they were tested as adults. Sign-tracking is thought to reflect the lever acquiring incentive salience (motivational value) as a result of its pairing with reward. Thus, KYNA exposure may increase the incentive salience of cues associated with reward, perhaps contributing to an increase in sensitivity to drug-related cues in persons with schizophrenia. In Experiment 2, we tested the effects of exposure to KYNA during adolescence on hippocampal long-term potentiation (LTP). Rats treated with L-KYN exhibited no LTP after a burst of high-frequency stimulation that was sufficient to produce robust LTP in vehicle-treated rats. This finding represents the first demonstrated consequence of elevated KYNA concentration during development and provides insight into the basis for cognitive and behavioral deficits that result from exposure to KYNA during adolescence

  4. Harmful potential toxic elements in greenhouse soils under long-term cultivation in Almería (Spain)

    NASA Astrophysics Data System (ADS)

    Joaquin Ramos-Miras, Jose; Rodríguez Martín, Jose Antonio; Boluda, Rafael; Bech, Jaume; Gil, Carlos

    2014-05-01

    Heavy metals (HM) are considered highly significant environmental contaminants and are the object of many scientific research works into the soil environment. Activities like agriculture or industry can increase the concentration of these contaminants in soils and waters, which can affect the food chain. Intensification of certain agricultural practices, constant and excessive use of fertilizers and phytosanitary products, and using machinery, increase the HM content in agricultural soils. Many studies have dealt with HM accumulation over time. Despite these works, the influence of long periods of time on these contents, the dynamics and evolution of these elements in agricultural soils, especially soils used for intensive farming purposes under greenhouse conditions, remain unknown to a certain extent. The western Almería region (Spain) is a very important area from both the socio-economic and agricultural viewpoints. A common practice in greenhouse agriculture is the addition of agrochemicals to soils and crops to improve nutrient supply or crop protection and disease control. Such intense agricultural activity has a strong impact, which may have negative repercussions on both these greenhouse soils and the environment. A research has been carried out to determine the total and available levels of six harmful potentially toxic elements (Cd, Cu, Pb, Ni, Zn and Co), and to assess long-term variations in the greenhouse soils of western Almeria. The results indicate that managing soils in the greenhouse preparation stage determines major changes in total and available HM contents. Furthermore, Cd, Cu and Pb enrichment in soil was observed depending on the element and years of growth.

  5. Identification of genes co-upregulated with Arc during BDNF-induced long-term potentiation in adult rat dentate gyrus in vivo.

    PubMed

    Wibrand, Karin; Messaoudi, Elhoucine; Håvik, Bjarte; Steenslid, Vibeke; Løvlie, Roger; Steen, Vidar M; Bramham, Clive R

    2006-03-01

    Brain-derived neurotrophic factor (BDNF) is a critical regulator of transcription-dependent adaptive neuronal responses, such as long-term potentiation (LTP). Brief infusion of BDNF into the dentate gyrus of adult anesthetized rats triggers stable LTP at medial perforant path-granule synapses that is transcription-dependent and requires induction of the immediate early gene Arc. Rather than acting alone, Arc is likely to be part of a larger BDNF-induced transcriptional program. Here, we used cDNA microarray expression profiling to search for genes co-upregulated with Arc 3 h after BDNF-LTP induction. Of nine cDNAs encoding for known genes and up-regulated more than four-fold, we selected five genes, Narp, neuritin, ADP-ribosylation factor-like protein-4 (ARL4L), TGF-beta-induced immediate early gene-1 (TIEG1) and CARP, for further validation. Real-time PCR confirmed robust up-regulation of these genes in an independent set of BDNF-LTP experiments, whereas infusion of the control protein cytochrome C had no effect. In situ hybridization histochemistry further revealed up-regulation of all five genes in somata of post-synaptic granule cells following both BDNF-LTP and high-frequency stimulation-induced LTP. While Arc synthesis is critical for local actin polymerization and stable LTP formation, several of the co-upregulated genes have known functions in excitatory synaptogenesis, axon guidance and glutamate receptor clustering. These results provide novel insight into gene expression responses underlying BDNF-induced synaptic consolidation in the adult brain in vivo. PMID:16553613

  6. Long-Term Effects of Child Corporal Punishment on Depressive Symptoms in Young Adults: Potential Moderators and Mediators

    ERIC Educational Resources Information Center

    Turner, Heather A.; Muller, Paul A.

    2004-01-01

    Based on a sample of 649 students from 3 New England colleges, this study examined the long-term effects of childhood corporal punishment on symptoms of depression and considered factors that may moderate or mediate the association. Similar to national studies, approximately 40% of the sample reported experiencing some level of corporal punishment…

  7. Understanding the relationship between actual and potential evapotranspirations from long- term water balance analysis and flux observation

    NASA Astrophysics Data System (ADS)

    Yang, D.; Yang, H.; Sun, F.

    2007-12-01

    potential evaporations are plotted against the time (year) during the same period. This means that complementary idea cannot provide universally correct predictions on the trend of actual evaporation only from the potential one. In this research, we examine the coupled water-energy balance based on Budyko hypothesis and proposed a conceptual model for predicting the inter-annual variability of annual water balance, and the change trends of water balances due to climate changes. The wet environment evaporation was defined as the boundary condition in the Bouchet hypothesis and introduced into complementary relationship (CR), which combined the actual evaporation with potential evaporation in an equation. However, the CR was derived in a closed system where no horizontal energy advection existed. The effect of the horizontal advection on the CR in a real open system was also analyzed in this study. Using the long-term water balance analysis in the 108 study catchments and flux observation at 7 sites in Asia monsoon region, the regional and seasonal variability of the complementary relationship was examined. Key Words: climate change, evapotranspiration, water balance, flux observation, Budyko hypothesis, Bouchet hypothesis

  8. Nitric Oxide Is Required for L-Type Ca2+ Channel-Dependent Long-Term Potentiation in the Hippocampus

    PubMed Central

    Pigott, Beatrice M.; Garthwaite, John

    2016-01-01

    Nitric oxide (NO) has long been implicated in the generation of long-term potentiation (LTP) and other types of synaptic plasticity, a role for which the intimate coupling between NMDA receptors (NMDARs) and the neuronal isoform of NO synthase (nNOS) is likely to be instrumental in many instances. While several types of synaptic plasticity depend on NMDARs, others do not, an example of which is LTP triggered by opening of L-type voltage-gated Ca2+ channels (L-VGCCs) in postsynaptic neurons. In CA3-CA1 synapses in the hippocampus, NMDAR-dependent LTP (LTPNMDAR) appears to be primarily expressed postsynaptically whereas L-VGCC-dependent LTP (LTPL−VGCC), which often coexists with LTPNMDAR, appears mainly to reflect enhanced presynaptic transmitter release. Since NO is an excellent candidate as a retrograde messenger mediating post-to-presynaptic signaling, we sought to determine if NO functions in LTPL−VGCC in mouse CA3-CA1 synapses. When elicited by a burst type of stimulation with NMDARs and the associated NO release blocked, LTPL−VGCC was curtailed by inhibition of NO synthase or of the NO-receptor guanylyl cyclase to the same extent as occurred with inhibition of L-VGCCs. Unlike LTPNMDAR at these synapses, LTPL−VGCC was unaffected in mice lacking endothelial NO synthase, implying that the major source of the NO is neuronal. Transient delivery of exogenous NO paired with tetanic synaptic stimulation under conditions of NMDAR blockade resulted in a long-lasting potentiation that was sensitive to inhibition of NO-receptor guanylyl cyclase but was unaffected by inhibition of L-VGCCs. The results indicate that NO, acting through its second messenger cGMP, plays an unexpectedly important role in L-VGCC-dependent, NMDAR-independent LTP, possibly as a retrograde messenger generated in response to opening of postsynaptic L-VGCCs and/or as a signal acting postsynaptically, perhaps to facilitate changes in gene expression. PMID:27445786

  9. The potential use of diisononyl phthalate metabolites hair as biomarkers to assess long-term exposure demonstrated by a rat model.

    PubMed

    Hsu, Jen-Yi; Ho, Hsin-Hui; Liao, Pao-Chi

    2015-01-01

    Diisononyl phthalate (DINP) is a widely used industrial plasticizer. People come into contact with this chemical by using plastic products made with it. Human health can be adversely affected by long-term DINP exposure. However, because the body rapidly excretes DINP metabolites, the use of single-point urine analysis to assess long-term exposure may produce inconsistent results in epidemiologic studies. Hair analysis has a useful place in biomonitoring, particularly in estimating long-term or historical exposure for some chemicals. Several studies have reported using hair analysis to assess the concentrations of heavy metals, drugs and organic pollutants in humans. As a biomarker, DINP metabolites were measured in rat hair in animal experiments to evaluated long-term exposure to DINP. In addition, we evaluated the correlation between the levels of DINP metabolites in hair and in urine. The levels of DINP metabolites in rat hair were significantly higher in the exposure group, relative to the control group (p<0.05). DINP metabolites had a positive correlation with increasing administered dose. Significant positive correlations for MINP, MOINP and MHINP were found between hair and urine (r=0.86, r=0.79 and r=0.74, respectively, p<0.05). Several metabolites in urine showed earlier saturation than in hair. In this report, we detected eight metabolites in hair and demonstrate that hair analysis has potential applications in the assessment of long-term exposure to DINP. PMID:25278043

  10. Potential of the solid-Earth response for limiting long-term West Antarctic Ice Sheet retreat

    NASA Astrophysics Data System (ADS)

    Konrad, Hannes; Sasgen, Ingo; Pollard, David; Klemann, Volker

    2016-04-01

    for asthenosphere viscosities of 3x10^20 Pa s or higher. References Gomez, N., Pollard, D., Mitrovica, J. X., Huybers, P., & Clark, P. U. (2012). Evolution of a coupled marine ice sheet-sea level model. J. Geophys. Res. 117(F1). Konrad, H., Sasgen, I., Pollard, D. & Klemann, V. (2015). Potential of the solid-Earth response for limiting long-term West Antarctic Ice Sheet retreat in a warming climate. Earth Planet. Sci. Lett. 432, 2015.

  11. Worldwide impact of aerosol’s time scale on the predicted long-term concentrating solar power potential

    NASA Astrophysics Data System (ADS)

    Ruiz-Arias, Jose A.; Gueymard, Christian A.; Santos-Alamillos, Francisco J.; Pozo-Vázquez, David

    2016-08-01

    Concentrating solar technologies, which are fuelled by the direct normal component of solar irradiance (DNI), are among the most promising solar technologies. Currently, the state-of the-art methods for DNI evaluation use datasets of aerosol optical depth (AOD) with only coarse (typically monthly) temporal resolution. Using daily AOD data from both site-specific observations at ground stations as well as gridded model estimates, a methodology is developed to evaluate how the calculated long-term DNI resource is affected by using AOD data averaged over periods from 1 to 30 days. It is demonstrated here that the use of monthly representations of AOD leads to systematic underestimations of the predicted long-term DNI up to 10% in some areas with high solar resource, which may result in detrimental consequences for the bankability of concentrating solar power projects. Recommendations for the use of either daily or monthly AOD data are provided on a geographical basis.

  12. Worldwide impact of aerosol’s time scale on the predicted long-term concentrating solar power potential

    PubMed Central

    Ruiz-Arias, Jose A.; Gueymard, Christian A.; Santos-Alamillos, Francisco J.; Pozo-Vázquez, David

    2016-01-01

    Concentrating solar technologies, which are fuelled by the direct normal component of solar irradiance (DNI), are among the most promising solar technologies. Currently, the state-of the-art methods for DNI evaluation use datasets of aerosol optical depth (AOD) with only coarse (typically monthly) temporal resolution. Using daily AOD data from both site-specific observations at ground stations as well as gridded model estimates, a methodology is developed to evaluate how the calculated long-term DNI resource is affected by using AOD data averaged over periods from 1 to 30 days. It is demonstrated here that the use of monthly representations of AOD leads to systematic underestimations of the predicted long-term DNI up to 10% in some areas with high solar resource, which may result in detrimental consequences for the bankability of concentrating solar power projects. Recommendations for the use of either daily or monthly AOD data are provided on a geographical basis. PMID:27507711

  13. Glacial ice composition: A potential long-term record of the chemistry of atmospheric deposition, Wind River Range, Wyoming

    SciTech Connect

    Naftz, D.L. ); Rice, J.A. ); Ranville, J.R. )

    1991-06-01

    During a reconnaissance study, ice samples were collected from Knife Point glacier to determine if glaciers in the Wind River Range Could provide a long-term record of the chemical composition of wet deposition. Eight annual ice layers comprising the years 1980-1987 were identified. The concentration of calcium, chloride, and sulfate in the annual-weighted wet deposition samples collected at the National Atmospheric deposition Program (NADP) station near Pinedale, Wyoming, showed a significant, positive correlation to the concentration of the same major ions in composite samples from the annual ice layers. results of the study imply that continuous ice cores reaching to the deeper parts of glaciers in the Wind River Range could provide long-term records of the chemical composition of wet deposition.

  14. Hippocampal long-term potentiation in adult Lurcher mutant mice: effect of embryonic cerebellar graft and motor training.

    PubMed

    Barcal, J; Cendelín, J; Vozeh, F

    2008-01-01

    Possible effect of trophic factors from embryonic cerebellar graft transplanted in adult Lurcher mutant mice on LTP as electrophysiological marker of learning and memory process was studied. Also the combination of the transplantation and long-term forced motor training was investigated. An evaluation of LTP ability in four animal groups (transplanted, sham-operated, with and without forced motor activity) and comparison among them showed the highest LTP improvement in the group with combination of both influences (ie. transplantation and motor training).

  15. Long-term potentiation and memory processes in the psychological works of Sigmund Freud and in the formation of neuropsychiatric symptoms.

    PubMed

    Centonze, D; Siracusano, A; Calabresi, P; Bernardi, G

    2005-01-01

    Far from disproving the model of mind functioning proposed by psychoanalysis, the recent advances in neuropsychiatrical research confirmed the crucial ideas of Sigmund Freud. The hypothesis that the origin of mental illnesses lies in the impossibility for a subject to erase the long-term effects of a remote adverse event is in tune with the view that several psychiatric disturbances reflect the activation of aberrant unconscious memory processes. Freud's insights did not stop here, but went on to describe in an extremely precise manner the neural mechanisms of memory formation almost a century before the description of long-term synaptic potentiation.

  16. Short- and long-term changes in right whale calling behavior: the potential effects of noise on acoustic communication.

    PubMed

    Parks, Susan E; Clark, C W; Tyack, P L

    2007-12-01

    The impact of anthropogenic noise on marine mammals has been an area of increasing concern over the past two decades. Most low-frequency anthropogenic noise in the ocean comes from commercial shipping which has contributed to an increase in ocean background noise over the past 150 years. The long-term impacts of these changes on marine mammals are not well understood. This paper describes both short- and long-term behavioral changes in calls produced by the endangered North Atlantic right whale (Eubalaena glacialis) and South Atlantic right whale (Eubalaena australis) in the presence of increased low-frequency noise. Right whales produce calls with a higher average fundamental frequency and they call at a lower rate in high noise conditions, possibly in response to masking from low-frequency noise. The long-term changes have occurred within the known lifespan of individual whales, indicating that a behavioral change, rather than selective pressure, has resulted in the observed differences. This study provides evidence of a behavioral change in sound production of right whales that is correlated with increased noise levels and indicates that right whales may shift call frequency to compensate for increased band-limited background noise.

  17. Emotional and Cognitive Information Processing: Relations to Behavioral Performance and Hippocampal Long-Term Potentiation In Vivo during a Spatial Water Maze Training in Rats

    ERIC Educational Resources Information Center

    Schulz, Kristina; Korz, Volker

    2010-01-01

    Emotionality as well as cognitive abilities contribute to the acquisition and retrieval of memories as well as to the consolidation of long-term potentiation (LTP), a cellular model of memory formation. However, little is known about the timescale and relative contribution of these processes. Therefore, we tested the effects of weak water maze…

  18. Assessing Potential Implications of Climate Change for Long-Term Water Resources Planning in the Colorado River Basin, Texas

    NASA Astrophysics Data System (ADS)

    Munevar, A.; Butler, S.; Anderson, R.; Rippole, J.

    2008-12-01

    exploring climate change projections and methods to assess potential impacts over the project's expected life. Following an initial qualitative risk assessment, quantitative climate scenarios were developed based on multiple coupled atmosphere-ocean general circulation model (AOGCM) simulations under a range of global emission scenarios. Projected temperature and precipitation changes were evaluated from 112 downscaled AOGCM projections. A Four scenarios were selected for detailed hydrologic evaluations using the Variable Infiltration Capacity (VIC) macroscale model. A quantile mapping procedure was applied to map future climatological period change statistics onto the long-term natural climate variability in the observed record. Simulated changes in runoff, river flow, evaporation, and evapotranspiration are used to generate adjustments to historical hydrology for assessment of potential changes to surface water availability, river water quality, riverine habitat, and Bay health. Projected temperature, precipitation, and atmospheric CO2 concentrations are used to estimate changes in agricultural demand. Sea level rise scenarios that include trends in Gulf Coast shelf subsidence are combined with changes in inflows to evaluate increased coastal erosion, upland migration of the estuary, and changes to the salinity regime. Results of the scenario-based analyses are being considered in the development of adaptive management strategies for future operations of the system and the proposed project.

  19. Brain-derived neurotrophic factor contributes to spinal long-term potentiation and mechanical hypersensitivity by activation of spinal microglia in rat.

    PubMed

    Zhou, Li-Jun; Yang, Tao; Wei, Xiao; Liu, Yong; Xin, Wen-Jun; Chen, Yuan; Pang, Rui-Ping; Zang, Ying; Li, Yong-Yong; Liu, Xian-Guo

    2011-02-01

    It has been shown that following peripheral nerve injury brain-derived neurotrophic factor (BDNF) released by activated microglia contributes to neuropathic pain, but whether BDNF affects the function of microglia is still unknown. In the present work we found that spinal application of BDNF, which induced long-term potentiation (LTP) of C-fiber evoked field potentials, activated spinal microglia in naïve animals, while pretreatment with microglia inhibitor minocycline blocked BDNF-induced LTP. In addition, following LTP induction by BDNF, both phosphorylated Src-family kinases (p-SFKs) and phosphorylated p38 mitogen-activated protein kinase (p-p38 MAPK) were up-regulated only in spinal microglia but not in neurons and astrocytes, whilst spinal application of SFKs inhibitor (PP2 or SU6656) or p38 MAPK inhibitor (SB203580) blocked BDNF-induced LTP and suppressed microglial activation. As spinal LTP at C-fiber synapses is considered to underlie neuropathic pain, we subsequently examined whether BDNF may contribute to mechanical hypersensitivity by activation of spinal microglia using spared nerve injury (SNI) model. Following SNI BDNF and TrkB receptor were up-regulated mainly in dorsal horn neurons and in activated microglia, and p-SFKs and p-p38 MAPK were increased exclusively in microglia. Intrathecal injection of BDNF scavenger TrkB-Fc starting before SNI, which prevented the behavioral sign of neuropathic pain, suppressed both microglial activation and the up-regulation of p-SFKs and p-p38 MAPK produced by SNI. Thus, the increased BDNF/TrkB signaling in spinal dorsal horn may contribute to neuropathic pain by activation of microglia following peripheral nerve injury and inhibition of SFKs or p38 MAPK may selectively inhibit microglia in spinal dorsal horn.

  20. Chronic Deep Cerebellar Stimulation Promotes Long-Term Potentiation, Microstructural Plasticity, and Reorganization of Perilesional Cortical Representation in a Rodent Model

    PubMed Central

    Cooperrider, Jessica; Furmaga, Havan; Plow, Ela; Park, Hyun-Joo; Chen, Zhihong; Kidd, Grahame; Baker, Kenneth B.; Gale, John T.

    2014-01-01

    Control over postinjury CNS plasticity is a major frontier of science that, if conquered, would open new avenues for treatment of neurological disorders. Here we investigate the functional, physiological, and structural changes in the cerebral cortex associated with chronic deep brain stimulation of the cerebellar output, a treatment approach that has been shown to improve postischemia motor recovery in a rodent model of cortical infarcts. Long–Evans rats were pretrained on the pasta-matrix retrieval task, followed by induction of focal cortical ischemia and implantation of a macroelectrode in the contralesional lateral cerebellar nucleus. Animals were assigned to one of three treatment groups pseudorandomly to balance severity of poststroke motor deficits: REGULAR stimulation, BURST stimulation, or SHAM. Treatment initiated 2 weeks post surgery and continued for 5 weeks. At the end, animals were randomly selected for perilesional intracortical microstimulation mapping and tissue sampling for Western blot analysis or contributed tissue for 3D electron microscopy. Evidence of enhanced cortical plasticity with therapeutically effective stimulation is shown, marked by greater perilesional reorganization in stimulation- treated animals versus SHAM. BURST stimulation was significantly effective for promoting distal forepaw cortical representation. Stimulation-treated animals showed a twofold increase in synaptic density compared with SHAM. In addition, treated animals demonstrated increased expression of synaptic markers of long-term potentiation and plasticity, including synaptophysin, NMDAR1, CaMKII, and PSD95. These findings provide a critical foundation of how deep cerebellar stimulation may guide plastic reparative reorganization after nonprogressive brain injury and indicate strong translational potential. PMID:24990924

  1. Potentials, Limitations and Applications of long-term and mobile ad-hoc Wireless Sensor Networks for Environmental Monitoring

    NASA Astrophysics Data System (ADS)

    Bumberger, Jan; Mollenhauer, Hannes; Lapteva, Yulia; Hutschenreuther, Tino; Toepfer, Hannes; Dietrich, Peter

    2014-05-01

    To characterize environmental systems it is necessary to identify and describe processes with suitable methods. Environmental systems are often characterized by their high heterogeneity, so individual measurements for their complete representation are often not sufficient. The application of wireless sensor networks in terrestrial and aquatic ecosystems offer significant benefits as a better consideration of the local test conditions becomes possible. This can be essential for the monitoring of heterogeneous environmental systems. Significant advantages in the application of mobile ad-hoc wireless sensor networks are their self-organizing behavior, resulting in a major reduction in installation and operation costs and time. In addition, a point measurement with a sensor is significantly improved by measuring at several points. It is also possible to perform analog and digital signal processing and computation on the basis of the measured data close to the sensor. Hence, a significant reduction of the data to be transmitted can be achieved which leads to a better energy management of sensor nodes. Furthermore, their localization via satellite, the miniaturization of the nodes and long-term energy self-sufficiency are current topics under investigation. The possibilities and limitations of the applicability of wireless sensor networks for long-term and mobile environmental monitoring are presented. A concepts and realization example are given in the field of micrometeorology and soil parameters for the interaction of biotic and abiotic processes .This long term monitoring is part of the Global Change Experimental Facility (GCEF), a large field-based experimental platform to assess the effects of climate change on ecosystem functions and processes under different land-use scenarios. Furthermore a mobile ad-hoc sensor network is presented for the monitoring of water induced mass wasting processes.

  2. Nicotine enhances the depressive actions of A beta 1-40 on long-term potentiation in the rat hippocampal CA1 region in vivo.

    PubMed

    Freir, D B; Herron, C E

    2003-06-01

    Hippocampal long-term potentiation (LTP) is a form of synaptic plasticity used as a cellular model of memory. Beta amyloid (A beta) is involved in Alzheimer's disease (AD), a neurode-generative disorder leading to cognitive deficits. Nicotine is also claimed to act as a cognitive enhancer. A beta is known to bind with high affinity to the alpha 7-nicotinic acetylcholine receptor (nAChR). Here we have investigated the effect of intracerebroventricular (i.c.v.) injection of the endogenous peptide A beta 1-40 on LTP in area CA1 of urethananesthetized rats. We also examined the effect of A beta 12-28 (i.c.v.), which binds with high affinity to the alpha 7-nAChR and the specific alpha 7-nAChR antagonist methyllycaconitine (MLA) on LTP. We found that A beta 12-28 had no effect on LTP, whereas MLA depressed significantly LTP, suggesting that activation of the alpha 7-nAChR is a requirement for LTP. Within the in vivo environment, where other factors may compete with A beta 12-28 for binding to alpha 7-nAChR, it does not appear to modulate LTP. To determine if the depressive action of A beta 1-40 on LTP could be modulated by nicotine, these agents were also co-applied. Injection of 1 or 10 nmol A beta 1-40 caused a significant depression of LTP, whereas nicotine alone (3 mg/kg) had no effect on LTP. Co-injection of nicotine with A beta 1-40 1 h prior to LTP induction caused a further significant depression of LTP compared with A beta 1-40 alone. These results demonstrate that nicotine enhances the deficit in LTP produced by A beta 1-40. This then suggests that nicotine may exacerbate the depressive actions of A beta on synaptic plasticity in AD.

  3. Alpha synuclein oligomers oppose long-term potentiation and impair memory through a calcineurin-dependent mechanism: relevance to human synucleopathic diseases

    PubMed Central

    Martin, Zane S.; Neugebauer, Volker; Dineley, Kelly T.; Kayed, Rakez; Zhang, Wenru; Reese, Lindsay C.; Taglialatela, Giulio

    2011-01-01

    Intracellular deposition of fibrillar aggregates of alpha synuclein (αSyn) characterizes neurodegenerative diseases such as Parkinson’s disease (PD) and dementia with Lewy bodies (DLB). However, recent evidence indicates that small αSyn oligomeric aggregates that precede fibril formation may be the most neurotoxic species and can be found extracellularly. This new evidence has changed the view of pathological αSyn aggregation from a self-contained cellular phenomenon to an extracellular event and prompted investigation of the putative effects of extracellular αSyn oligomers. Here, we report that extracellular application of αSyn oligomers detrimentally impacts neuronal welfare and memory function. We found that oligomeric αSyn increased intracellular Ca2+ levels, induced calcineurin (CaN) activity, decreased cAMP response element binding protein (CREB) transcriptional activity and resulted in calcineurin-dependent death of human neuroblastoma cells. Similarily, CaN induction and CREB inhibition were observed when αSyn oligomers were applied to organotypic brain slices, which opposed hippocampal long-term potentiation (LTP). Furthermore, αSyn oligomers induced CaN, inhibited CREB and evoked memory impairments in mice that received acute intracerebroventricular injections. Notably, all these events were reversed by pharmacological inhibition of CaN. Moreover, we found decreased active calcineurin (CaN) and reduced levels of phosphorylated CREB in autopsy brain tissue from patients affected by DLB, which is characterized by deposition of αSyn aggregates and progressive cognitive decline. These results indicate that exogenously-applied αSyn oligomers impact neuronal function and produce memory deficits through mechanisms that involve CaN activation. PMID:22060133

  4. Streptozotocin Induces Mild Cognitive Impairment at Appropriate Doses in Mice as Determined by Long-Term Potentiation and the Morris Water Maze.

    PubMed

    Li, Dong; Huang, Yan; Cheng, Bin; Su, Jie; Zhou, Wen-Xia; Zhang, Yong-Xiang

    2016-07-27

    Alzheimer's disease (AD) is a progressive neurodegenerative disease, and effective therapeutic drugs in the clinic are still lacking. Ideally, AD progression could be stopped at an early stage, such as at the mild cognitive impairment (MCI) stage. MCI refers to the clinical condition between normal aging and dementia. Patients with MCI experience memory loss but do not meet the criteria for the diagnosis of clinically probable AD. However, few MCI animal models have been established. Here, we used in vivo long-term potentiation (LTP) recording and the Morris water maze (MWM) to evaluate the effects of intracerebroventricular injection of streptozotocin (ICV-STZ) in mice. We found a relationship between cognitive behavior and LTP in vivo and determined the appropriate doses of STZ for a putative MCI animal model. Animals that received≥150μg of STZ exhibited cognitive impairment in the MWM test, and few changes in behavior tests were observed in animals receiving less than 150μg of STZ. In vivo LTP recordings revealed that the induction of LTP decreased significantly in STZ-treated animals, even at the lowest dose (25μg/mouse), in a dose-dependent manner. Pathology analysis revealed STZ-induced neuron loss in a dose-dependent manner, both in the cortex and in the hippocampus, as evidenced by a significantly decreased neuronal number in the cohort treated with 75μg of STZ/mouse. Our study indicated that a low dose (25μg/mouse) of STZ impaired neural plasticity; at a higher dose of 75μg/mouse STZ, further LTP deficits were noted along with induced neuronal loss in both the cortex and the hippocampus, which could be considered a possible MCI or pre-MCI animal model; and finally, at 150μg/mouse STZ, dementia was induced, feasibly indicating a state of AD.

  5. Role of Sialidase in Long-Term Potentiation at Mossy Fiber-CA3 Synapses and Hippocampus-Dependent Spatial Memory

    PubMed Central

    Minami, Akira; Saito, Masakazu; Mamada, Shou; Ieno, Daisuke; Hikita, Tomoya; Takahashi, Tadanobu; Otsubo, Tadamune; Ikeda, Kiyoshi; Suzuki, Takashi

    2016-01-01

    Sialic acid bound to glycans in glycolipids and glycoproteins is essential for synaptic plasticity and memory. Sialidase (EC 3.2.1.18), which has 4 isozymes including Neu1, Neu2, Neu3 and Neu4, regulates the sialylation level of glycans by removing sialic acid from sialylglycoconjugate. In the present study, we investigated the distribution of sialidase activity in rat hippocampus and the role of sialidase in hippocampal memory processing. We previously developed a highly sensitive histochemical imaging probe for sialidase activity, BTP3-Neu5Ac. BTP3-Neu5Ac was cleaved efficiently by rat Neu2 and Neu4 at pH 7.3 and by Neu1 and Neu3 at pH 4.6. When a rat hippocampal acute slice was stained with BTP3-Neu5Ac at pH 7.3, mossy fiber terminal fields showed relatively intense sialidase activity. Thus, the role of sialidase in the synaptic plasticity was investigated at mossy fiber terminal fields. The long-term potentiation (LTP) at mossy fiber-CA3 pyramidal cell synapses was impaired by 2,3-dehydro-2-deoxy-N-acetylneuraminic acid (DANA), a sialidase inhibitor. DANA also failed to decrease paired-pulse facilitation after LTP induction. We also investigated the role of sialidase in hippocampus-dependent spatial memory by using the Morris water maze. The escape latency time to reach the platform was prolonged by DANA injection into the hippocampal CA3 region or by knockdown of Neu4 without affecting motility. The results show that the regulation of sialyl signaling by Neu4 is involved in hippocampal memory processing. PMID:27783694

  6. Ras-GRF2 mediates long-term potentiation, survival, and response to an enriched environment of newborn neurons in the hippocampus.

    PubMed

    Darcy, Michael J; Trouche, Stéphanie; Jin, Shan-Xue; Feig, Larry A

    2014-11-01

    Hippocampal adult neurogenesis contributes to key functions of the dentate gyrus (DG), including contextual discrimination. This is due, at least in part, to the unique form of plasticity that new neurons display at a specific stage of their development when compared with the surrounding principal neurons. In addition, the contribution that newborn neurons make to dentate function can be enhanced by an increase in their numbers induced by a stimulating environment. However, signaling mechanisms that regulate these properties of newborn neurons are poorly understood. Here, we show that Ras-GRF2 (GRF2), a calcium-regulated exchange factor that can activate Ras and Rac GTPases, contributes to both of these properties of newborn neurons. Using Ras-GRF2 knockout mice and wild-type mice stereotactically injected with retrovirus containing shRNA against the exchange factor, we demonstrate that GRF2 promotes the survival of newborn neurons of the DG at approximately 1-2 weeks after their birth. GRF2 also controls the distinct form of long-term potentiation that is characteristic of new neurons of the hippocampus through its effector Erk MAP kinase. Moreover, the enhancement of neuron survival that occurs after mice are exposed to an enriched environment also involves GRF2 function. Consistent with these observations, GRF2 knockout mice display defective contextual discrimination. Overall, these findings indicate that GRF2 regulates both the basal level and environmentally induced increase of newborn neuron survival, as well as in the induction of a distinct form of synaptic plasticity of newborn neurons that contributes to distinct features of hippocampus-derived learning and memory.

  7. Influx of extracellular Zn(2+) into the hippocampal CA1 neurons is required for cognitive performance via long-term potentiation.

    PubMed

    Takeda, A; Suzuki, M; Tempaku, M; Ohashi, K; Tamano, H

    2015-09-24

    Physiological significance of synaptic Zn(2+) signaling was examined in the CA1 of young rats. In vivo CA1 long-term potentiation (LTP) was induced using a recording electrode attached to a microdialysis probe and the recording region was locally perfused with artificial cerebrospinal fluid (ACSF) via the microdialysis probe. In vivo CA1 LTP was inhibited under perfusion with CaEDTA and ZnAF-2DA, extracellular and intracellular Zn(2+) chelators, respectively, suggesting that the influx of extracellular Zn(2+) is required for in vivo CA1 LTP induction. The increase in intracellular Zn(2+) was chelated with intracellular ZnAF-2 in the CA1 1h after local injection of ZnAF-2DA into the CA1, suggesting that intracellular Zn(2+) signaling induced during learning is blocked with intracellular ZnAF-2 when the learning was performed 1h after ZnAF-2DA injection. Object recognition was affected when training of object recognition test was performed 1h after ZnAF-2DA injection. These data suggest that intracellular Zn(2+) signaling in the CA1 is required for object recognition memory via LTP. Surprisingly, in vivo CA1 LTP was affected under perfusion with 0.1-1μM ZnCl2, unlike the previous data that in vitro CA1 LTP was enhanced in the presence of 1-5μM ZnCl2. The influx of extracellular Zn(2+) into CA1 pyramidal cells has bidirectional action in CA1 LTP. The present study indicates that the degree of extracellular Zn(2+) influx into CA1 neurons is critical for LTP and cognitive performance. PMID:26204819

  8. Acquisition of contextual discrimination involves the appearance of a RAS-GRF1/p38 mitogen-activated protein (MAP) kinase-mediated signaling pathway that promotes long term potentiation (LTP).

    PubMed

    Jin, Shan-Xue; Arai, Junko; Tian, Xuejun; Kumar-Singh, Rajendra; Feig, Larry A

    2013-07-26

    RAS-GRF1 is a guanine nucleotide exchange factor with the ability to activate RAS and RAC GTPases in response to elevated calcium levels. We previously showed that beginning at 1 month of age, RAS-GRF1 mediates NMDA-type glutamate receptor (NMDAR)-induction of long term depression in the CA1 region of the hippocampus of mice. Here we show that beginning at 2 months of age, when mice first acquire the ability to discriminate between closely related contexts, RAS-GRF1 begins to contribute to the induction of long term potentiation (LTP) in the CA1 hippocampus by mediating the action of calcium-permeable, AMPA-type glutamate receptors (CP-AMPARs). Surprisingly, LTP induction by CP-AMPARs through RAS-GRF1 occurs via activation of p38 MAP kinase rather than ERK MAP kinase, which has more frequently been linked to LTP. Moreover, contextual discrimination is blocked by knockdown of Ras-Grf1 expression specifically in the CA1 hippocampus, infusion of a p38 MAP kinase inhibitor into the CA1 hippocampus, or the injection of an inhibitor of CP-AMPARs. These findings implicate the CA1 hippocampus in the developmentally dependent capacity to distinguish closely related contexts through the appearance of a novel LTP-supporting signaling pathway.

  9. Forever Young(er): potential age-defying effects of long-term meditation on gray matter atrophy

    PubMed Central

    Luders, Eileen; Cherbuin, Nicolas; Kurth, Florian

    2015-01-01

    While overall life expectancy has been increasing, the human brain still begins deteriorating after the first two decades of life and continues degrading further with increasing age. Thus, techniques that diminish the negative impact of aging on the brain are desirable. Existing research, although scarce, suggests meditation to be an attractive candidate in the quest for an accessible and inexpensive, efficacious remedy. Here, we examined the link between age and cerebral gray matter re-analyzing a large sample (n = 100) of long-term meditators and control subjects aged between 24 and 77 years. When correlating global and local gray matter with age, we detected negative correlations within both controls and meditators, suggesting a decline over time. However, the slopes of the regression lines were steeper and the correlation coefficients were stronger in controls than in meditators. Moreover, the age-affected brain regions were much more extended in controls than in meditators, with significant group-by-age interactions in numerous clusters throughout the brain. Altogether, these findings seem to suggest less age-related gray matter atrophy in long-term meditation practitioners. PMID:25653628

  10. Evaluating long-term annual sediment yield estimating potential of GIS interfaced MUSLE model on two micro-watersheds.

    PubMed

    Arekhi, Saleh

    2008-01-15

    Use of an event scale MUSLE model for obtaining accurate long-term annual sediment yield estimates from micro-watersheds was evaluated. Such estimates are extremely important for designing appropriate soil/water conserving measures. For easy extraction and inputting of model input parameters, the proposed model was interfaced to an Arc-View/Spatial Analyst geographic information system. Application of this GIS interfaced MUSLE model on two gauged (pine and oak forest) hilly micro-watersheds viz., Salla Rautella (0.47 km2) and Naula (0.42 km2), in Almora district of Uttaranchal, India showed that it could estimate annual sediment yields with absolute mean relative errors ranging between 12-14%. Even long-term average sediment yields for Salla Rautella (observed: 9.58 tons and estimated: 10.92 tons) and Naula: (Observed: 23.89 tons and estimated: 26.61 tons) micro-watersheds could be quite realistically simulated by the proposed model. PMID:18817202

  11. Long-Term Quiescent Fibroblast Cells Transit into Senescence

    PubMed Central

    Marthandan, Shiva; Priebe, Steffen; Hemmerich, Peter; Klement, Karolin; Diekmann, Stephan

    2014-01-01

    Cellular senescence is described to be a consequence of telomere erosion during the replicative life span of primary human cells. Quiescence should therefore not contribute to cellular aging but rather extend lifespan. Here we tested this hypothesis and demonstrate that cultured long-term quiescent human fibroblasts transit into senescence due to similar cellular mechanisms with similar dynamics and with a similar maximum life span as proliferating controls, even under physiological oxygen conditions. Both, long-term quiescent and senescent fibroblasts almost completely fail to undergo apoptosis. The transition of long-term quiescent fibroblasts into senescence is also independent of HES1 which protects short-term quiescent cells from becoming senescent. Most significantly, DNA damage accumulates during senescence as well as during long-term quiescence at physiological oxygen levels. We suggest that telomere-independent, potentially maintenance driven gradual induction of cellular senescence during quiescence is a counterbalance to tumor development. PMID:25531649

  12. The effect of extensive reading and paired-associate learning on long-term vocabulary retention: an event-related potential study.

    PubMed

    Chun, Eunjin; Choi, Sungmook; Kim, Junsoo

    2012-07-19

    We investigated the relative efficacy of extensive reading (ER) and paired-associate learning (PAL) in the ability of second language (L2) learners to retain new vocabulary words. To that end, we combined behavioral measures (i.e., vocabulary tests) and an event-related potential (ERP) investigation with a focus on the N400 ERP component to track short- and long-term vocabulary retention as a consequence of the two different approaches. Behavioral results indicated that both ER and PAL led to substantial short-term retention of the target words. In contrast, on a long-term basis, ER was more effective than PAL to a considerable degree as indicated by a large-size effect (d=1.35). Evidence from the N400 effects (d=1.70) observed in the parietal electrode group (P3, Pz, P4) provided further support for the superior effects of ER over PAL on long-term vocabulary retention. The converging evidence challenges the assumptions of some L2 researchers and makes a significant contribution to the literature of vocabulary acquisition, because it provides the first ERP evidence that ER is more conducive to long-term vocabulary retention than PAL.

  13. Autonomous isolation, long-term culture and differentiation potential of adult salivary gland-derived stem/progenitor cells.

    PubMed

    Baek, Hyunjung; Noh, Yoo Hun; Lee, Joo Hee; Yeon, Soo-In; Jeong, Jaemin; Kwon, Heechung

    2014-09-01

    Salivary gland stem/progenitor cells belong to the endodermal lineage and may serve as good candidates to replace their dysfunctional counterparts. The objective of this study was to isolate large numbers of salivary gland tissue-derived stem cells (SGSCs) from adult rats in order to develop a clinically applicable method that does not involve sorting or stem cell induction by duct ligation. We analysed SGSCs isolated from normal rat salivary glands to determine whether they retained the major characteristics of stem cells, self-renewal and multipotency, especially with respect to the various endodermal cell types. SGSCs expressed high levels of integrin α6β1 and c-kit, which are surface markers of SGSCs. In particular, the integrin α6β1(+) /c-kit(+) salivary gland cells maintained the morphology, proliferation activity and multipotency of stem cells for up to 92 passages in 12 months. Furthermore, we analysed the capacity of SGSCs to differentiate into endoderm lineage cell types, such as acinar-like and insulin-secreting cells. When cultured on growth factor reduced matrigel, the morphology of progenitor cells changed to acinar-like structures and these cells expressed the acinar cell-specific marker, α-amylase, and tight junction markers. Moreover, reverse transcription-polymerase chain reaction (RT-PCR) data showed increased expression of pancreatic cell markers, including insulin, Pdx1, pan polypeptide and neurogenin-3, when these cells formed pancreatic clusters in the presence of activin A, exendin-4 and retinoic acid. These data demonstrate that adult salivary stem/progenitor cells may serve as a potential source for cell therapy in salivary gland hypofunction and diabetes.

  14. Mice lacking the PSD-95-interacting E3 ligase, Dorfin/Rnf19a, display reduced adult neurogenesis, enhanced long-term potentiation, and impaired contextual fear conditioning.

    PubMed

    Park, Hanwool; Yang, Jinhee; Kim, Ryunhee; Li, Yan; Lee, Yeunkum; Lee, Chungwoo; Park, Jongil; Lee, Dongmin; Kim, Hyun; Kim, Eunjoon

    2015-11-10

    Protein ubiquitination has a significant influence on diverse aspects of neuronal development and function. Dorfin, also known as Rnf19a, is a RING finger E3 ubiquitin ligase implicated in amyotrophic lateral sclerosis and Parkinson's disease, but its in vivo functions have not been explored. We report here that Dorfin is a novel binding partner of the excitatory postsynaptic scaffolding protein PSD-95. Dorfin-mutant (Dorfin(-/-)) mice show reduced adult neurogenesis and enhanced long-term potentiation in the hippocampal dentate gyrus, but normal long-term potentiation in the CA1 region. Behaviorally, Dorfin(-/-) mice show impaired contextual fear conditioning, but normal levels of cued fear conditioning, fear extinction, spatial learning and memory, object recognition memory, spatial working memory, and pattern separation. Using a proteomic approach, we also identify a number of proteins whose ubiquitination levels are decreased in the Dorfin(-/-) brain. These results suggest that Dorfin may regulate adult neurogenesis, synaptic plasticity, and contextual fear memory.

  15. Simvastatin Enhances Spatial Memory and Long-Term Potentiation in Hippocampal CA1 via Upregulation of α7 Nicotinic Acetylcholine Receptor.

    PubMed

    Chen, Tingting; Wang, Conghui; Sha, Sha; Zhou, Libin; Chen, Lei; Chen, Ling

    2016-08-01

    Simvastatin (SV) has been reported to improve cognitive deficits in Alzheimer's disease. Here, we show that chronic administration of SV (20 mg/kg) for 30 days in adult mice (SV mice) enhanced spatial cognitive performance as assessed by Morris water maze and Y-maze. To explore mechanisms underlying SV-enhanced spatial cognition, we further examined synaptic properties and long-term potentiation (LTP) in hippocampal CA1, hippocampal α7nAChR expression, and Akt and ERK2 phosphorylation. In comparison with controls, the SV administration caused increase in presynaptic glutamate release and amplitude of NMDAr-dependent LTP (LTP-augmentation), and decrease in threshold of NMDAr-independent LTP induction (LTP-facilitation). The supplement of isoprenoid farnesyl pyrophosphate (FPP) by applying farnesol (FOH) could abolish the spatial cognitive potentiation, increased glutamate release, and LTP-augmentation/facilitation in SV mice. Expression of α7nAChR, but not α4β2nAChR, was increased in hippocampal pyramidal cells of SV mice with the reduction of transcription factor AP-2α, which were abolished by FOH. Levels of Akt and ERK2 phosphorylation in SV mice were elevated, which were suppressed by FOH or α7nAChR antagonist methyl-lycaconitine (MLA). In hippocampal slices obtained from SV mice, acute perfusion of MLA blocked the increased glutamate release, whereas FOH, PI3K inhibitor LY294002, or MEK inhibitor U0126 could not. In the slices of SV mice, the perfusion of MLA or U0126, but not FOH, abolished the LTP-augmentation and LTP-facilitation. By contrast, LY294002 prevented the LTP-facilitation but failed to affect the LTP-augmentation. The findings indicate that the administration of SV through reducing FPP increases α7nAChR expression and α7nAChR-related Akt and ERK2 phosphorylation, leading to LTP enhancement and spatial cognitive potentiation.

  16. Long-Term Water-Quality Changes in East Fork Poplar Creek, Tennessee: Background, Trends, and Potential Biological Consequences

    NASA Astrophysics Data System (ADS)

    Stewart, Arthur J.; Smith, John G.; Loar, James M.

    2011-06-01

    We review long-term changes that have occurred in factors affecting water quality in East Fork Poplar Creek (EFPC; in East Tennessee) over a nearly 25-year monitoring period. Historically, the stream has received wastewaters and pollutants from a major United States Department of Energy (DOE) facility on the headwaters of the stream. Early in the monitoring program, EFPC was perturbed chemically, especially within its headwaters; evidence of this perturbation extended downstream for many kilometers. The magnitude of this perturbation, and the concentrations of many biologically significant water-quality factors, has lessened substantially through time. The changes in water-quality factors resulted from a large number of operational changes and remedial actions implemented at the DOE facility. Chief among these were consolidation and elimination of many effluents, elimination of an unlined settling/flow equalization basin, reduction in amount of blow-down from cooling tower operations, dechlorination of effluents, and implementation of flow augmentation. Although many water-quality characteristics in upper EFPC have become more similar to those of reference streams, conditions remain far from pristine. Nutrient enrichment may be one of the more challenging problems remaining before further biological improvements occur.

  17. Long-term water-quality changes in East Fork Poplar Creek, Tennessee: background, trends, and potential biological consequences.

    PubMed

    Stewart, Arthur J; Smith, John G; Loar, James M

    2011-06-01

    We review long-term changes that have occurred in factors affecting water quality in East Fork Poplar Creek (EFPC; in East Tennessee) over a nearly 25-year monitoring period. Historically, the stream has received wastewaters and pollutants from a major United States Department of Energy (DOE) facility on the headwaters of the stream. Early in the monitoring program, EFPC was perturbed chemically, especially within its headwaters; evidence of this perturbation extended downstream for many kilometers. The magnitude of this perturbation, and the concentrations of many biologically significant water-quality factors, has lessened substantially through time. The changes in water-quality factors resulted from a large number of operational changes and remedial actions implemented at the DOE facility. Chief among these were consolidation and elimination of many effluents, elimination of an unlined settling/flow equalization basin, reduction in amount of blow-down from cooling tower operations, dechlorination of effluents, and implementation of flow augmentation. Although many water-quality characteristics in upper EFPC have become more similar to those of reference streams, conditions remain far from pristine. Nutrient enrichment may be one of the more challenging problems remaining before further biological improvements occur. PMID:21380789

  18. Impact of long-term treatment of onchocerciasis with ivermectin in Ecuador: potential for elimination of infection

    PubMed Central

    Vieira, Juan Carlos; Cooper, Philip J; Lovato, Raquel; Mancero, Tamara; Rivera, Jorge; Proaño, Roberto; López, Andrea A; Guderian, Ronald H; Guzmán, José Rumbea

    2007-01-01

    Background Onchocerciasis is a leading cause of blindness worldwide, hence elimination of the infection is an important health priority. Community-based treatment programs with ivermectin form the basis of control programs for the disease in Latin America. The long-term administration of ivermectin could eliminate Onchocerca volvulus infection from endemic areas in Latin America. Methods A strategy of annual to twice-annual treatments with ivermectin has been used for onchocerciasis in endemic communities in Ecuador for up to 14 years. The impact of ivermectin treatment on ocular morbidity, and O. volvulus infection and transmission was monitored in seven sentinel communities. Results Over the period 1990–2003, high rates of treatment coverage of the eligible population were maintained in endemic communities (mean 85.2% per treatment round). Ivermectin reduced the prevalence of anterior segment disease of the eye to 0% in sentinel communities and had a major impact on the prevalence and transmission of infection, with possible elimination of infection in some foci. Conclusion The distribution of ivermectin in endemic communities in Ecuador might have eliminated ocular morbidity and significant progress has been made towards elimination of the infection. A strategy of more frequent treatments with ivermectin may be required in communities where the infection persists to achieve the objective of elimination of the infection from Ecuador. The elimination of the infection from an endemic country in Latin America would be a major public health achievement and could stimulate the implementation of elimination strategies in other endemic countries. PMID:17521449

  19. Predicting ecosystem carbon balance in a warming Arctic: the importance of long-term thermal acclimation potential and inhibitory effects of light on respiration.

    PubMed

    McLaughlin, Blair C; Xu, Cheng-Yuan; Rastetter, Edward B; Griffin, Kevin L

    2014-06-01

    The carbon balance of Arctic ecosystems is particularly sensitive to global environmental change. Leaf respiration (R), a temperature-dependent key process in determining the carbon balance, is not well-understood in Arctic plants. The potential for plants to acclimate to warmer conditions could strongly impact future global carbon balance. Two key unanswered questions are (1) whether short-term temperature responses can predict long-term respiratory responses to growth in elevated temperatures and (2) to what extent the constant daylight conditions of the Arctic growing season inhibit leaf respiration. In two dominant Arctic species Eriophorum vaginatum (tussock grass) and Betula nana (woody shrub), we assessed the extent of respiratory inhibition in the light (RL/RD), respiratory response to short-term temperature change, and respiratory acclimation to long-term warming treatments. We found that R of both species is strongly inhibited by light (averaging 35% across all measurement temperatures). In E. vaginatum both RL and RD acclimated to the long-term warming treatment, reducing the magnitude of respiratory response relative to the short-term response to temperature increase. In B. nana, both RL and RD responded to short-term temperature increase but showed no acclimation to the long-term warming. The ability to predict plant respiratory response to global warming with short-term temperature responses will depend on species-specific acclimation potential and the differential response of RL and RD to temperature. With projected woody shrub encroachment in Arctic tundra and continued warming, changing species dominance between these two functional groups, may impact ecosystem respiratory response and carbon balance. PMID:24677488

  20. Predicting ecosystem carbon balance in a warming Arctic: the importance of long-term thermal acclimation potential and inhibitory effects of light on respiration.

    PubMed

    McLaughlin, Blair C; Xu, Cheng-Yuan; Rastetter, Edward B; Griffin, Kevin L

    2014-06-01

    The carbon balance of Arctic ecosystems is particularly sensitive to global environmental change. Leaf respiration (R), a temperature-dependent key process in determining the carbon balance, is not well-understood in Arctic plants. The potential for plants to acclimate to warmer conditions could strongly impact future global carbon balance. Two key unanswered questions are (1) whether short-term temperature responses can predict long-term respiratory responses to growth in elevated temperatures and (2) to what extent the constant daylight conditions of the Arctic growing season inhibit leaf respiration. In two dominant Arctic species Eriophorum vaginatum (tussock grass) and Betula nana (woody shrub), we assessed the extent of respiratory inhibition in the light (RL/RD), respiratory response to short-term temperature change, and respiratory acclimation to long-term warming treatments. We found that R of both species is strongly inhibited by light (averaging 35% across all measurement temperatures). In E. vaginatum both RL and RD acclimated to the long-term warming treatment, reducing the magnitude of respiratory response relative to the short-term response to temperature increase. In B. nana, both RL and RD responded to short-term temperature increase but showed no acclimation to the long-term warming. The ability to predict plant respiratory response to global warming with short-term temperature responses will depend on species-specific acclimation potential and the differential response of RL and RD to temperature. With projected woody shrub encroachment in Arctic tundra and continued warming, changing species dominance between these two functional groups, may impact ecosystem respiratory response and carbon balance.

  1. Potential role of surface wettability on the long-term stability of dentin bonds after surface biomodification

    PubMed Central

    Leme, Ariene A.; Vidal, Cristina M. P.; Hassan, Lina Saleh; Bedran-Russo, Ana K.

    2015-01-01

    Degradation of the adhesive interface contributes to the failure of resin composite restorations. The hydrophilicity of the dentin matrix during and after bonding procedures may result in an adhesive interface that is more prone to degradation over time. This study assessed the effect of chemical modification of dentin matrix on the wettability and the long-term reduced modulus of elasticity (Er) of the adhesive interfaces. Human molars were divided into groups according to the priming solutions: distilled water (control), 6.5% Proanthocyanidin-rich grape seed extract (PACs), 5.75% 1-ethyl-3-[3-dimethylaminopropyl] carbodiimide hydrochloride/1.4% n-hydroxysuccinimide (EDC/NHS) and 5% Glutaraldehyde (GA). The water-surface contact angle was verified before and after chemical modification of the dentin matrix. The demineralized dentin surface was treated with the priming solutions and restored with One Step Plus (OS) and Single Bond Plus (SB) and resin composite. The Er of the adhesive, hybrid layer and underlying dentin was evaluated after 24 h and 30 months in artificial saliva. The dentin hydrophilicity significantly decreased after application of the priming solutions. Aging significantly decreased the Er in the hybrid layer and underlying dentin of control groups. The Er of GA groups remained stable over time at the hybrid layer and underlying dentin. Significant higher Er was observed for PACs and EDC/NHS groups at the hybrid layer after 24 h. The decreased hydrophilicity of the modified dentin matrix likely influence the immediate mechanical properties of the hybrid layer. Dentin biomodification prevented substantial aging at the hybrid layer and underlying dentin after 30 months storage. PMID:25869721

  2. Gene expression profile in long-term non progressor HIV infected patients: in search of potential resistance factors.

    PubMed

    Luque, Maria Carolina; Santos, Camila C; Mairena, Eliane C; Wilkinson, Peter; Boucher, Genèvieve; Segurado, Aluisio C; Fonseca, Luiz A; Sabino, Ester; Kalil, Jorge E; Cunha-Neto, Edecio

    2014-11-01

    Long-term non-progressors (LTNP) represent a minority (1-5%) of HIV-infected individuals characterized by documented infection for more than 7-10 years, a stable CD4+ T cell count over 500/mm(3) and low viremia in the absence of antiretroviral treatment. Protective factors described so far such as the CCR5delta32 deletion, protective HLA alleles, or defective viruses fail to fully explain the partial protection phenotype. The existence of additional host resistance mechanisms in LTNP patients was investigated here using a whole human genome microarray study comparing gene expression profiles of unstimulated peripheral blood mononuclear cells from LTNP patients, HIV-1 infected patients under antiretroviral therapy with CD4+ T cell levels above 500/mm(3) (ST), as well as healthy individuals. Genes that were up- or downregulated exclusively in LTNP, ST or in both groups in comparison to controls were identified and classified in functional categories using Ingenuity Pathway Analysis. ST and LTNP patient groups revealed distinct genetic profiles, regarding gene number in each category and up- or downregulation of specific genes, which could have a bearing on the outcome of each group. We selected some relevant genes to validate the differential expression using quantitative real-time qRT-PCR. Among others, we found several genes related to the canonical Wnt/beta-catenin signaling pathway. Our results identify new possible host genes and molecules that could be involved in the mechanisms leading to the slower progression to AIDS and sustained CD4+ T cell counts that is peculiar to LTNP patients.

  3. Potential role of surface wettability on the long-term stability of dentin bonds after surface biomodification.

    PubMed

    Leme, Ariene A; Vidal, Cristina M P; Hassan, Lina Saleh; Bedran-Russo, Ana K

    2015-07-16

    Degradation of the adhesive interface contributes to the failure of resin composite restorations. The hydrophilicity of the dentin matrix during and after bonding procedures may result in an adhesive interface that is more prone to degradation over time. This study assessed the effect of chemical modification of the dentin matrix on the wettability and the long-term reduced modulus of elasticity (Er) of adhesive interfaces. Human molars were divided into groups according to the priming solutions: distilled water (control), 6.5% Proanthocyanidin-rich grape seed extract (PACs), 5.75% 1-ethyl-3-[3-dimethylaminopropyl] carbodiimide hydrochloride/1.4% n-hydroxysuccinimide (EDC/NHS) and 5% Glutaraldehyde (GA). The water-surface contact angle was assessed before and after chemical modification of the dentin matrix. The demineralized dentin surface was treated with the priming solutions and restored with One Step Plus (OS) and Single Bond Plus (SB) and resin composite. Er of the adhesive, hybrid layer and underlying dentin was evaluated after 24h and 30 months in artificial saliva. The dentin hydrophilicity significantly decreased after application of the priming solutions. Aging significantly decreased Er in the hybrid layer and underlying dentin of control groups. Er of GA groups remained stable over time at the hybrid layer and underlying dentin. Significant higher Er was observed for PACs and EDC/NHS groups at the hybrid layer after 24h. The decreased hydrophilicity of the modified dentin matrix likely influence the immediate mechanical properties of the hybrid layer. Dentin biomodification prevented substantial aging at the hybrid layer and underlying dentin after 30 months storage.

  4. Global climate change in large European rivers: long-term effects on macroinvertebrate communities and potential local confounding factors.

    PubMed

    Floury, Mathieu; Usseglio-Polatera, Philippe; Ferreol, Martial; Delattre, Cecile; Souchon, Yves

    2013-04-01

    Aquatic species living in running waters are widely acknowledged to be vulnerable to climate-induced, thermal and hydrological fluctuations. Climate changes can interact with other environmental changes to determine structural and functional attributes of communities. Although such complex interactions are most likely to occur in a multiple-stressor context as frequently encountered in large rivers, they have received little attention in such ecosystems. In this study, we aimed at specifically addressing the issue of relative long-term effects of global and local changes on benthic macroinvertebrate communities in multistressed large rivers. We assessed effects of hydroclimatic vs. water quality factors on invertebrate community structure and composition over 30 years (1979-2008) in the Middle Loire River, France. As observed in other large European rivers, water warming over the three decades (+0.9 °C between 1979-1988 and 1999-2008) and to a lesser extent discharge reduction (-80 m(3) s(-1) ) were significantly involved in the disappearance or decrease in taxa typical from fast running, cold waters (e.g. Chloroperlidae and Potamanthidae). They explained also a major part of the appearance and increase of taxa typical from slow flowing or standing waters and warmer temperatures, including invasive species (e.g. Corbicula sp. and Atyaephyra desmarestii). However, this shift towards a generalist and pollution tolerant assemblage was partially confounded by local improvement in water quality (i.e. phosphate input reduction by about two thirds and eutrophication limitation by almost one half), explaining a significant part of the settlement of new pollution-sensitive taxa (e.g. the caddisfly Brachycentridae and Philopotamidae families) during the last years of the study period. The regain in such taxa allowed maintaining a certain level of specialization in the invertebrate community despite climate change effects.

  5. Long-term decoding stability of local field potentials from silicon arrays in primate motor cortex during a 2D center out task

    NASA Astrophysics Data System (ADS)

    Wang, Dong; Zhang, Qiaosheng; Li, Yue; Wang, Yiwen; Zhu, Junming; Zhang, Shaomin; Zheng, Xiaoxiang

    2014-06-01

    Objective. Many serious concerns exist in the long-term stability of brain-machine interfaces (BMIs) based on spike signals (single unit activity, SUA; multi unit activity, MUA). Some studies showed local field potentials (LFPs) could offer a stable decoding performance. However, the decoding stability of LFPs was examined only when high quality spike signals were recorded. Here we aim to examine the long-term decoding stability of LFPs over a larger time scale when the quality of spike signals was from good to poor or even no spike was recorded. Approach. Neural signals were collected from motor cortex of three monkeys via silicon arrays over 230, 290 and 690 days post-implantation when they performed 2D center out task. To compare long-term stability between LFPs and spike signals, we examined them in neural signals characteristics, directional tuning properties and offline decoding performance, respectively. Main results. We observed slow decreasing trends in the number of LFP channels recorded and mean LFP power in different frequency bands when spike signals quality decayed over time. The number of significantly directional tuning LFP channels decreased more slowly than that of tuning SUA and MUA. The variable preferred directions for the same signal features across sessions indicated non-stationarity of neural activity. We also found that LFPs achieved better decoding performance than SUA and MUA in retrained decoder when the quality of spike signals seriously decayed. Especially, when no spike was recorded in one monkey after 671 days post-implantation, LFPs still provided some kinematic information. In addition, LFPs outperformed MUA in long-term decoding stability in a static decoder. Significance. Our results suggested that LFPs were more durable and could provide better decoding performance when spike signals quality seriously decayed. It might be due to their resistance to recording degradation and their high redundancy among channels.

  6. Impaired long-term expansion and self-renewal potential of pediatric acute myeloid leukemia-initiating cells by PTK787/ZK 222584.

    PubMed

    Weidenaar, Alida C; Ter Elst, Arja; Kampen, Kim R; Meeuwsen-de Boer, Tiny; Kamps, Willem A; Schuringa, Jan Jacob; de Bont, Eveline S J M

    2013-04-01

    Although most children with acute myeloid leukemia (AML) achieve complete remission, the relapse rate is 30% to 40%. Because it is thought that leukemia-initiating cells (LIC) are responsible for AML relapses, targeting these cells might improve outcome. Treatment of pediatric AML blasts with the receptor tyrosine kinase (RTK) inhibitor PTK787/ZK 222584 (PTK/ZK) induces cell death in vitro. However, the role of PTK/ZK inhibition on outgrowth of (pediatric) LICs is unknown. In this study, we cultured CD34+ cells from pediatric patients with AML on MS5 stromal cells in long-term cocultures. In analogy to adult AML, long-term expansion of leukemic cells up to 10 weeks could be generated in 9 of 13 pediatric AMLs. Addition of PTK/ZK to long-term cocultures significantly inhibited leukemic expansion in all samples, ranging from 4% to 80% growth inhibition at week 5 compared with untreated samples. In 75% of the samples, the inhibitory effect was more pronounced at week 10. Proteome profiler array analysis of downstream kinases revealed that PTK/ZK reduced activation of PI3K/Akt kinase signaling. Although main targets of PTK/ZK are VEGF receptors (VEGFR), no effect was seen on outgrowth of LICs when cultured with bevacizumab (monoclonal VEGFA-antibody), specific antibodies against VEGFR2 or VEGFR3, or exposed to stroma-derived VEGFA. These data suggest that the effect of PTK/ZK on LICs is not only dependent on inhibition of VEGFA/VEGFR signaling. Taken together, our data elucidated antileukemic properties of PTK/ZK in long-term expansion cultures, and suggest that targeting multiple RTKs by PTK/ZK might be a potential effective approach in eradicating (pediatric) LICs. PMID:23393162

  7. Intestinal healing after anti-TNF induction therapy predicts long-term response to one-year treatment in patients with ileocolonic Crohn’s disease naive to anti-TNF agents

    PubMed Central

    Łykowska-Szuber, Liliana; Katulska, Katarzyna; Stawczyk-Eder, Kamila; Krela-Kaźmierczak, Iwona; Klimczak, Katarzyna; Szymczak, Aleksandra; Stajgis, Marek; Linke, Krzysztof

    2015-01-01

    Introduction Objective assessment of Crohn’s disease (CD) activity in patients treated with anti-tumour necrosis factor (anti-TNF) antibodies is crucial for the prediction of its long-term results. Mucosal healing estimated endoscopically has a strong predictive value; however, only combined assessment together with transmural healing in magnetic resonance enterography (MRE) gives full information about the whole spectrum of inflammatory lesions in CD. Aim To assess the usefulness of intestinal healing phenomenon in CD, defined as improvement both in endoscopy and MRE, after anti-TNF induction therapy, in predicting long-term results of 1-year treatment. Material and methods Twenty-six patients with ileocolonic CD were enrolled into the study. In this group a parallel assessment of disease activity was estimated before and after induction doses of anti-TNF antibodies with ileocolonoscopy and MRE by using appropriate scores. Subsequently the patients were treated until 12 months and then followed-up. The associations between intestinal healing (assessed in MRE and endoscopy), and mucosal and transmural healing with long-term results of 1-year anti-TNF therapy were analysed statistically. Results The median time of follow-up was 29 months (interquartile range – IQR: 14–46). Intestinal healing was significantly associated with favourable therapeutic outcomes (p = 0.02) and had 75% (IQR: 35–97%) sensitivity and 72% (IQR: 46–90%) specificity in predicting long-term remission. Other parameters were not useful (transmural healing) or their usefulness was of borderline significance (mucosal healing). Conclusions Dynamic assessment of intestinal healing is an accurate method in predicting long-term outcomes in CD patients responding to 1-year anti-TNF therapy.

  8. Encapsulated living choroid plexus cells: potential long-term treatments for central nervous system disease and trauma.

    PubMed

    Skinner, S J M; Geaney, M S; Lin, H; Muzina, M; Anal, A K; Elliott, R B; Tan, P L J

    2009-12-01

    . Previously reported evidence demonstrated that CP cells support the survival and differentiation of neuronal cells in vitro and effectively treat acute brain injury and disease in rodents and non-human primates in vivo. The accumulated preclinical data together with the long-term survival of implanted encapsulated cells in vivo provide a sound base for the investigation of these treatments for chronic inherited and established neurodegenerative conditions.

  9. Encapsulated living choroid plexus cells: potential long-term treatments for central nervous system disease and trauma

    NASA Astrophysics Data System (ADS)

    Skinner, S. J. M.; Geaney, M. S.; Lin, H.; Muzina, M.; Anal, A. K.; Elliott, R. B.; Tan, P. L. J.

    2009-12-01

    . Previously reported evidence demonstrated that CP cells support the survival and differentiation of neuronal cells in vitro and effectively treat acute brain injury and disease in rodents and non-human primates in vivo. The accumulated preclinical data together with the long-term survival of implanted encapsulated cells in vivo provide a sound base for the investigation of these treatments for chronic inherited and established neurodegenerative conditions.

  10. The effects of prolonged administration of norepinephrine reuptake inhibitors on long-term potentiation in dentate gyrus, and on tests of spatial and object recognition memory in rats.

    PubMed

    Walling, Susan G; Milway, J Stephen; Ingram, Matthew; Lau, Catherine; Morrison, Gillian; Martin, Gerard M

    2016-02-01

    Phasic norepinephrine (NE) release events are involved in arousal, novelty detection and in plasticity processes underlying learning and memory in mammalian systems. Although the effects of phasic NE release events on plasticity and memory are prevalently documented, it is less understood what effects chronic NE reuptake inhibition and sustained increases in noradrenergic tone, might have on plasticity and cognitive processes in rodent models of learning and memory. This study investigates the effects of chronic NE reuptake inhibition on hippocampal plasticity and memory in rats. Rats were administered NE reuptake inhibitors (NRIs) desipramine (DMI; 0, 3, or 7.5mg/kg/day) or nortriptyline (NTP; 0, 10 or 20mg/kg/day) in drinking water. Long-term potentiation (LTP; 200 Hz) of the perforant path-dentate gyrus evoked potential was examined in urethane anesthetized rats after 30-32 days of DMI treatment. Short- (4-h) and long-term (24-h) spatial memory was tested in separate rats administered 0 or 7.5mg/kg/day DMI (25-30 days) using a two-trial spatial memory test. Additionally, the effects of chronically administered DMI and NTP were tested in rats using a two-trial, Object Recognition Test (ORT) at 2- and 24-h after 45 and 60 days of drug administration. Rats administered 3 or 7.5mg/kg/day DMI had attenuated LTP of the EPSP slope but not the population spike at the perforant path-dentate gyrus synapse. Short- and long-term memory for objects is differentially disrupted in rats after prolonged administration of DMI and NTP. Rats that were administered 7.5mg/kg/day DMI showed decreased memory for a two-trial spatial task when tested at 4-h. In the novel ORT, rats receiving 0 or 7.5mg/kg/day DMI showed a preference for the arm containing a Novel object when tested at both 2- and 24-h demonstrating both short- and long-term memory retention of the Familiar object. Rats that received either dose of NTP or 3mg/kg/day DMI showed impaired memory at 2-h, however this

  11. Long Term Exposure to Polyphenols of Artichoke (Cynara scolymus L.) Exerts Induction of Senescence Driven Growth Arrest in the MDA-MB231 Human Breast Cancer Cell Line.

    PubMed

    Mileo, Anna Maria; Di Venere, Donato; Abbruzzese, Claudia; Miccadei, Stefania

    2015-01-01

    Polyphenolic extracts from the edible part of artichoke (Cynara scolymus L.) have been shown to be potential chemopreventive and anticancer dietary compounds. High doses of polyphenolic extracts (AEs) induce apoptosis and decrease the invasive potential of the human breast cancer cell line, MDA-MB231. However, the molecular mechanism underlying AEs antiproliferative effects is not completely understood. We demonstrate that chronic and low doses of AEs treatment at sublethal concentrations suppress human breast cancer cell growth via a caspases-independent mechanism. Furthermore, AEs exposure induces a significant increase of senescence-associated β-galactosidase (SA-β-gal) staining and upregulation of tumour suppressor genes, p16(INK4a) and p21(Cip1/Waf1) in MDA-MB231 cells. AEs treatment leads to epigenetic alterations in cancer cells, modulating DNA hypomethylation and lysine acetylation levels in total proteins. Cell growth arrest correlates with increased reactive oxygen species (ROS) production in AEs treated breast cancer cells. Inhibition of ROS generation by N-acetylcysteine (NAC) attenuates the antiproliferative effect. These findings demonstrate that chronic AEs treatment inhibits breast cancer cell growth via the induction of premature senescence through epigenetic and ROS-mediated mechanisms. Our results suggest that artichoke polyphenols could be a promising dietary tool either in cancer chemoprevention or/and in cancer treatment as a nonconventional, adjuvant therapy. PMID:26180585

  12. Long Term Exposure to Polyphenols of Artichoke (Cynara scolymus L.) Exerts Induction of Senescence Driven Growth Arrest in the MDA-MB231 Human Breast Cancer Cell Line.

    PubMed

    Mileo, Anna Maria; Di Venere, Donato; Abbruzzese, Claudia; Miccadei, Stefania

    2015-01-01

    Polyphenolic extracts from the edible part of artichoke (Cynara scolymus L.) have been shown to be potential chemopreventive and anticancer dietary compounds. High doses of polyphenolic extracts (AEs) induce apoptosis and decrease the invasive potential of the human breast cancer cell line, MDA-MB231. However, the molecular mechanism underlying AEs antiproliferative effects is not completely understood. We demonstrate that chronic and low doses of AEs treatment at sublethal concentrations suppress human breast cancer cell growth via a caspases-independent mechanism. Furthermore, AEs exposure induces a significant increase of senescence-associated β-galactosidase (SA-β-gal) staining and upregulation of tumour suppressor genes, p16(INK4a) and p21(Cip1/Waf1) in MDA-MB231 cells. AEs treatment leads to epigenetic alterations in cancer cells, modulating DNA hypomethylation and lysine acetylation levels in total proteins. Cell growth arrest correlates with increased reactive oxygen species (ROS) production in AEs treated breast cancer cells. Inhibition of ROS generation by N-acetylcysteine (NAC) attenuates the antiproliferative effect. These findings demonstrate that chronic AEs treatment inhibits breast cancer cell growth via the induction of premature senescence through epigenetic and ROS-mediated mechanisms. Our results suggest that artichoke polyphenols could be a promising dietary tool either in cancer chemoprevention or/and in cancer treatment as a nonconventional, adjuvant therapy.

  13. Long Term Exposure to Polyphenols of Artichoke (Cynara scolymus L.) Exerts Induction of Senescence Driven Growth Arrest in the MDA-MB231 Human Breast Cancer Cell Line

    PubMed Central

    Mileo, Anna Maria; Di Venere, Donato; Abbruzzese, Claudia; Miccadei, Stefania

    2015-01-01

    Polyphenolic extracts from the edible part of artichoke (Cynara scolymus L.) have been shown to be potential chemopreventive and anticancer dietary compounds. High doses of polyphenolic extracts (AEs) induce apoptosis and decrease the invasive potential of the human breast cancer cell line, MDA-MB231. However, the molecular mechanism underlying AEs antiproliferative effects is not completely understood. We demonstrate that chronic and low doses of AEs treatment at sublethal concentrations suppress human breast cancer cell growth via a caspases-independent mechanism. Furthermore, AEs exposure induces a significant increase of senescence-associated β-galactosidase (SA-β-gal) staining and upregulation of tumour suppressor genes, p16INK4a and p21Cip1/Waf1 in MDA-MB231 cells. AEs treatment leads to epigenetic alterations in cancer cells, modulating DNA hypomethylation and lysine acetylation levels in total proteins. Cell growth arrest correlates with increased reactive oxygen species (ROS) production in AEs treated breast cancer cells. Inhibition of ROS generation by N-acetylcysteine (NAC) attenuates the antiproliferative effect. These findings demonstrate that chronic AEs treatment inhibits breast cancer cell growth via the induction of premature senescence through epigenetic and ROS-mediated mechanisms. Our results suggest that artichoke polyphenols could be a promising dietary tool either in cancer chemoprevention or/and in cancer treatment as a nonconventional, adjuvant therapy. PMID:26180585

  14. NMDA receptor-dependent long-term potentiation comprises a family of temporally overlapping forms of synaptic plasticity that are induced by different patterns of stimulation

    PubMed Central

    Park, Pojeong; Volianskis, Arturas; Sanderson, Thomas M.; Bortolotto, Zuner A.; Jane, David E.; Zhuo, Min; Kaang, Bong-Kiun; Collingridge, Graham L.

    2014-01-01

    N-methyl-d-aspartate receptor (NMDAR)-dependent long-term potentiation (LTP) is extensively studied since it is believed to use the same molecular mechanisms that are required for many forms of learning and memory. Unfortunately, many controversies exist, not least the seemingly simple issue concerning the locus of expression of LTP. Here, we review our recent work and some of the extensive literature on this topic and present new data that collectively suggest that LTP can be explained, during its first few hours, by the coexistence of at least three mechanistically distinct processes that are all triggered by the synaptic activation of NMDARs. PMID:24298134

  15. Enhanced long term potentiation and decreased AMPA receptor desensitization in the acute period following a single kainate induced early life seizure.

    PubMed

    O'Leary, Heather; Bernard, Paul B; Castano, Anna M; Benke, Tim A

    2016-03-01

    Neonatal seizures are associated with long term disabilities including epilepsy and cognitive deficits. Using a neonatal seizure rat model that does not develop epilepsy, but develops a phenotype consistent with other models of intellectual disability (ID) and autism spectrum disorders (ASD), we sought to isolate the acute effects of a single episode of early life seizure on hippocampal CA1 synaptic development and plasticity. We have previously shown chronic changes in glutamatergic synapses, loss of long term potentiation (LTP) and enhanced long term depression (LTD), in the adult male rat ~50days following kainic acid (KA) induced early life seizure (KA-ELS) in post-natal (P) 7day old male Sprague-Dawley rats. In the present work, we examined the electrophysiological properties and expression levels of glutamate receptors in the acute period, 2 and 7days, post KA-ELS. Our results show for the first time enhanced LTP 7days after KA-ELS, but no change 2days post KA-ELS. Additionally, we report that ionotropic α-amino-3-hydroxy-5-methyl-isoxazole-propionic acid type glutamate receptor (AMPAR) desensitization is decreased in the same time frame, with no changes in AMPAR expression, phosphorylation, or membrane insertion. Inappropriate enhancement of the synaptic connections in the acute period after the seizure could alter the normal patterning of synaptic development in the hippocampus during this critical period and contribute to learning deficits. Thus, this study demonstrates a novel mechanism by which KA-ELS alters early network properties that potentially lead to adverse outcomes. PMID:26706598

  16. Serum aminoacylase-1 is a novel biomarker with potential prognostic utility for long-term outcome in patients with delayed graft function following renal transplantation.

    PubMed

    Welberry Smith, Matthew P; Zougman, Alexandre; Cairns, David A; Wilson, Michelle; Wind, Tobias; Wood, Steven L; Thompson, Douglas; Messenger, Michael P; Mooney, Andrew; Selby, Peter J; Lewington, Andrew J P; Banks, Rosamonde E

    2013-12-01

    Early identification and prognostic stratification of delayed graft function following renal transplantation has significant potential to improve outcome. Mass spectrometry analysis of serum samples, before and on day 2 post transplant from five patients with delayed graft function and five with an uncomplicated transplant, identified aminoacylase-1 (ACY-1) as a potential outcome biomarker. Following assay development, analysis of longitudinal samples from an initial validation cohort of 55 patients confirmed that the ACY-1 level on day 1 or 2 was a moderate predictor of delayed graft function, similar to serum creatinine, complementing the strongest predictor cystatin C. A further validation cohort of 194 patients confirmed this association with area under ROC curves (95% CI) for day 1 serum (138 patients) of 0.74 (0.67-0.85) for ACY-1, 0.9 (0.84-0.95) for cystatin C, and 0.93 (0.88-0.97) for both combined. Significant differences in serum ACY-1 levels were apparent between delayed, slow, and immediate graft function. Analysis of long-term follow-up for 54 patients with delayed graft function showed a highly significant association between day 1 or 3 serum ACY-1 and dialysis-free survival, mainly associated with the donor-brain-dead transplant type. Thus, proteomic analysis provides novel insights into the potential clinical utility of serum ACY-1 levels immediately post transplantation, enabling subdivision of patients with delayed graft function in terms of long-term outcome. Our study requires independent confirmation.

  17. Virtual Models of Long-Term Care

    ERIC Educational Resources Information Center

    Phenice, Lillian A.; Griffore, Robert J.

    2012-01-01

    Nursing homes, assisted living facilities and home-care organizations, use web sites to describe their services to potential consumers. This virtual ethnographic study developed models representing how potential consumers may understand this information using data from web sites of 69 long-term-care providers. The content of long-term-care web…

  18. The coumarin scopoletin potentiates acetylcholine release from synaptosomes, amplifies hippocampal long-term potentiation and ameliorates anticholinergic- and age-impaired memory

    PubMed Central

    Hornick, A.; Lieb, A.; Vo, N.P.; Rollinger, J.M.; Stuppner, H.; Prast, H.

    2011-01-01

    In a previous study the simple, naturally derived coumarin scopoletin (SCT) was identified as an inhibitor of acetylcholinesterase (AChE), using a pharmacophore-based virtual screening approach. In this study the potential of SCT as procholinergic and cognition-enhancing therapeutic was investigated in a more detailed way, using different experimental approaches like measuring newly synthesized acetylcholine (ACh) in synaptosomes, long-term potentiation (LTP) experiments in hippocampal slices, and behavior studies. SCT enhanced the K+-stimulated release of ACh from rat frontal cortex synaptosomes, showing a bell-shaped dose effect curve (Emax: 4 μM). This effect was blocked by the nicotinic ACh receptor (nAChR) antagonists mecamylamine (MEC) and dihydro-β-erythroidine (DHE). The nAChR agonist (and AChE inhibitor) galantamine induced a similar increase in ACh release (Emax: 1 μM). SCT potentiated LTP in hippocampal slices of rat brain. The high-frequency stimulation (HFS)-induced, N-methyl-D-aspartate (NMDA) receptor dependent LTP of field excitatory postsynaptic potentials at CA3-CA1 synapses was greatly enhanced by pre-HFS application of SCT (4 μM for 4 min). This effect was mimicked by nicotine (2 μM) and abolished by MEC, suggesting an effect on nAChRs. SCT did not restore the total inhibition of LTP by NMDA receptor antagonist d, l-2-amino-5-phosphonopentanoic acid (AP-5). SCT (2 μg, i.c.v.) increased T-maze alternation and ameliorated novel object recognition of mice with scopolamine-induced cholinergic deficit. It also reduced age-associated deficits in object memory of 15–18-month-old mice (2 mg/kg sc). Our findings suggest that SCT possesses memory-improving properties, which are based on its direct nAChR agonistic activity. Therefore, SCT might be able to rescue impaired cholinergic functions by enhancing nAChR-mediated release of neurotransmitters and promoting neural plasticity in hippocampus. PMID:21945033

  19. Long-Term Fructose Intake Increases Adipogenic Potential: Evidence of Direct Effects of Fructose on Adipocyte Precursor Cells

    PubMed Central

    Zubiría, María Guillermina; Alzamendi, Ana; Moreno, Griselda; Rey, María Amanda; Spinedi, Eduardo; Giovambattista, Andrés

    2016-01-01

    We have previously addressed that fructose rich diet (FRD) intake for three weeks increases the adipogenic potential of stromal vascular fraction cells from the retroperitoneal adipose tissue (RPAT). We have now evaluated the effect of prolonged FRD intake (eight weeks) on metabolic parameters, number of adipocyte precursor cells (APCs) and in vitro adipogenic potential from control (CTR) and FRD adult male rats. Additionally, we have examined the direct fructose effects on the adipogenic capacity of normal APCs. FRD fed rats had increased plasma levels of insulin, triglyceride and leptin, and RPAT mass and adipocyte size. FACS studies showed higher APCs number and adipogenic potential in FRD RPAT pads; data is supported by high mRNA levels of competency markers: PPARγ2 and Zfp423. Complementary in vitro experiments indicate that fructose-exposed normal APCs displayed an overall increased adipogenic capacity. We conclude that the RPAT mass expansion observed in eight week-FRD fed rats depends on combined accelerated adipogenesis and adipocyte hypertrophy, partially due to a direct effect of fructose on APCs. PMID:27049396

  20. Leptin attenuates the detrimental effects of β-amyloid on spatial memory and hippocampal later-phase long term potentiation in rats.

    PubMed

    Tong, Jia-Qing; Zhang, Jun; Hao, Ming; Yang, Ju; Han, Yu-Fei; Liu, Xiao-Jie; Shi, Hui; Wu, Mei-Na; Liu, Qing-Song; Qi, Jin-Shun

    2015-07-01

    β-Amyloid (Aβ) is the main component of amyloid plaques developed in the brain of patients with Alzheimer's disease (AD). The increasing burden of Aβ in the cortex and hippocampus is closely correlated with memory loss and cognition deficits in AD. Recently, leptin, a 16kD peptide derived mainly from white adipocyte tissue, has been appreciated for its neuroprotective function, although less is known about the effects of leptin on spatial memory and synaptic plasticity. The present study investigated the neuroprotective effects of leptin against Aβ-induced deficits in spatial memory and in vivo hippocampal late-phase long-term potentiation (L-LTP) in rats. Y maze spontaneous alternation was used to assess short term working memory, and the Morris water maze task was used to assess long term reference memory. Hippocampal field potential recordings were performed to observe changes in L-LTP. We found that chronically intracerebroventricular injection of leptin (1μg) effectively alleviated Aβ1-42 (20μg)-induced spatial memory impairments of Y maze spontaneous alternation and Morris water maze. In addition, chronic administration of leptin also reversed Aβ1-42-induced suppression of in vivo hippocampal L-LTP in rats. Together, these results suggest that chronic leptin treatments reversed Aβ-induced deficits in learning and memory and the maintenance of L-LTP.

  1. FOXC1 maintains the hair follicle stem cell niche and governs stem cell quiescence to preserve long-term tissue-regenerating potential.

    PubMed

    Lay, Kenneth; Kume, Tsutomu; Fuchs, Elaine

    2016-03-15

    Adult tissue stem cells (SCs) reside in niches, which orchestrate SC behavior. SCs are typically used sparingly and exist in quiescence unless activated for tissue growth. Whether parsimonious SC use is essential to conserve long-term tissue-regenerating potential during normal homeostasis remains poorly understood. Here, we examine this issue by conditionally ablating a key transcription factor Forkhead box C1 (FOXC1) expressed in hair follicle SCs (HFSCs). FOXC1-deficient HFSCs spend less time in quiescence, leading to markedly shortened resting periods between hair cycles. The enhanced hair cycling accelerates HFSC expenditure, and impacts hair regeneration in aging mice. Interestingly, although FOXC1-deficient HFs can still form a new bulge that houses HFSCs for the next hair cycle, the older bulge is left unanchored. As the new hair emerges, the entire old bulge, including its reserve HFSCs and SC-inhibitory inner cell layer, is lost. We trace this mechanism first, to a marked increase in cell cycle-associated transcripts upon Foxc1 ablation, and second, to a downstream reduction in E-cadherin-mediated inter-SC adhesion. Finally, we show that when the old bulge is lost with each hair cycle, overall levels of SC-inhibitory factors are reduced, further lowering the threshold for HFSC activity. Taken together, our findings suggest that HFSCs have restricted potential in vivo, which they conserve by coupling quiescence to adhesion-mediated niche maintenance, thereby achieving long-term tissue homeostasis.

  2. FOXC1 maintains the hair follicle stem cell niche and governs stem cell quiescence to preserve long-term tissue-regenerating potential.

    PubMed

    Lay, Kenneth; Kume, Tsutomu; Fuchs, Elaine

    2016-03-15

    Adult tissue stem cells (SCs) reside in niches, which orchestrate SC behavior. SCs are typically used sparingly and exist in quiescence unless activated for tissue growth. Whether parsimonious SC use is essential to conserve long-term tissue-regenerating potential during normal homeostasis remains poorly understood. Here, we examine this issue by conditionally ablating a key transcription factor Forkhead box C1 (FOXC1) expressed in hair follicle SCs (HFSCs). FOXC1-deficient HFSCs spend less time in quiescence, leading to markedly shortened resting periods between hair cycles. The enhanced hair cycling accelerates HFSC expenditure, and impacts hair regeneration in aging mice. Interestingly, although FOXC1-deficient HFs can still form a new bulge that houses HFSCs for the next hair cycle, the older bulge is left unanchored. As the new hair emerges, the entire old bulge, including its reserve HFSCs and SC-inhibitory inner cell layer, is lost. We trace this mechanism first, to a marked increase in cell cycle-associated transcripts upon Foxc1 ablation, and second, to a downstream reduction in E-cadherin-mediated inter-SC adhesion. Finally, we show that when the old bulge is lost with each hair cycle, overall levels of SC-inhibitory factors are reduced, further lowering the threshold for HFSC activity. Taken together, our findings suggest that HFSCs have restricted potential in vivo, which they conserve by coupling quiescence to adhesion-mediated niche maintenance, thereby achieving long-term tissue homeostasis. PMID:26912458

  3. FXR1P limits long-term memory, long-lasting synaptic potentiation, and de novo GluA2 translation.

    PubMed

    Cook, Denise; Nuro, Erin; Jones, Emma V; Altimimi, Haider F; Farmer, W Todd; Gandin, Valentina; Hanna, Edith; Zong, Ruiting; Barbon, Alessandro; Nelson, David L; Topisirovic, Ivan; Rochford, Joseph; Stellwagen, David; Béïque, Jean-Claude; Murai, Keith K

    2014-11-20

    Translational control of mRNAs allows for rapid and selective changes in synaptic protein expression that are required for long-lasting plasticity and memory formation in the brain. Fragile X Related Protein 1 (FXR1P) is an RNA-binding protein that controls mRNA translation in nonneuronal cells and colocalizes with translational machinery in neurons. However, its neuronal mRNA targets and role in the brain are unknown. Here, we demonstrate that removal of FXR1P from the forebrain of postnatal mice selectively enhances long-term storage of spatial memories, hippocampal late-phase long-term potentiation (L-LTP), and de novo GluA2 synthesis. Furthermore, FXR1P binds specifically to the 5' UTR of GluA2 mRNA to repress translation and limit the amount of GluA2 that is incorporated at potentiated synapses. This study uncovers a mechanism for regulating long-lasting synaptic plasticity and spatial memory formation and reveals an unexpected divergent role of FXR1P among Fragile X proteins in brain plasticity.

  4. FOXC1 maintains the hair follicle stem cell niche and governs stem cell quiescence to preserve long-term tissue-regenerating potential

    PubMed Central

    Lay, Kenneth; Kume, Tsutomu; Fuchs, Elaine

    2016-01-01

    Adult tissue stem cells (SCs) reside in niches, which orchestrate SC behavior. SCs are typically used sparingly and exist in quiescence unless activated for tissue growth. Whether parsimonious SC use is essential to conserve long-term tissue-regenerating potential during normal homeostasis remains poorly understood. Here, we examine this issue by conditionally ablating a key transcription factor Forkhead box C1 (FOXC1) expressed in hair follicle SCs (HFSCs). FOXC1-deficient HFSCs spend less time in quiescence, leading to markedly shortened resting periods between hair cycles. The enhanced hair cycling accelerates HFSC expenditure, and impacts hair regeneration in aging mice. Interestingly, although FOXC1-deficient HFs can still form a new bulge that houses HFSCs for the next hair cycle, the older bulge is left unanchored. As the new hair emerges, the entire old bulge, including its reserve HFSCs and SC-inhibitory inner cell layer, is lost. We trace this mechanism first, to a marked increase in cell cycle-associated transcripts upon Foxc1 ablation, and second, to a downstream reduction in E-cadherin–mediated inter-SC adhesion. Finally, we show that when the old bulge is lost with each hair cycle, overall levels of SC-inhibitory factors are reduced, further lowering the threshold for HFSC activity. Taken together, our findings suggest that HFSCs have restricted potential in vivo, which they conserve by coupling quiescence to adhesion-mediated niche maintenance, thereby achieving long-term tissue homeostasis. PMID:26912458

  5. Long-term Trend of Cold Air Mass Amount below a Designated Potential Temperature in Northern and Southern Hemisphere Winters with 7 Different Reanalysis Datasets

    NASA Astrophysics Data System (ADS)

    Kanno, Y.; Abdillah, M. R.; Iwasaki, T.

    2015-12-01

    This study addresses that the hemispheric total cold air mass amount defined below a threshold potential temperature of 280 K is a good indicator of the long-term trend of climate change in the polar region. We demonstrate quantitative analyses of warming trend in the Northern Hemisphere (NH) and Southern Hemisphere (SH) winters, using 7 different reanalysis datasets (JRA-55, JRA-55C, JRA-55AMIP, ERA-interim, CFSR, JRA-25, NCEP-NCAR). Hemispheric total cold air mass amount in the NH winter exhibit a statistically significant decreasing trend in all reanalysis datasets at a rate about -1.37 to -0.77% per decade over the period 1959-2012 and at a rate about -1.57 to -0.82% per decade over 1980-2012. There is no statistically significant trend in the equatorward cold air mass flux across latitude of 45N, which is an indicator for hemispheric-scale cold air outbreak, over the period 1980-2012 except for NCEP-NCAR reanalysis dataset which shows substantial decreasing trend of about -3.28% per decade. The spatial distribution of the long-term trend of cold air mass amount in the NH winter is almost consistent among reanalysis datasets except for JRA-55AMIP over the period 1980-2012. Cold air mass amount increases over Central Siberia, Kamchatka peninsula, and Bering Sea, while it decreases over Norwegian Sea, Barents Sea, Kara Sea, Greenland, Canada, Northern part of United States, and East Asia. In the SH winter, on the other hand, there is a large discrepancy in hemispheric total cold air mass amount and equatorward cold air mass flux across latitude of 50S over the period 1980-2010 among reanalysis datasets. This result indicate that there is a large uncertainty in the long-term trend of cold air mass amount in the SH winter.

  6. Conditional ablation of the neural cell adhesion molecule reduces precision of spatial learning, long-term potentiation, and depression in the CA1 subfield of mouse hippocampus.

    PubMed

    Bukalo, Olena; Fentrop, Nikolas; Lee, Alan Y W; Salmen, Benedikt; Law, Janice W S; Wotjak, Carsten T; Schweizer, Michaela; Dityatev, Alexander; Schachner, Melitta

    2004-02-18

    NCAM, a neural cell adhesion molecule of the immunoglobulin superfamily, is involved in neuronal migration and differentiation, axon outgrowth and fasciculation, and synaptic plasticity. To dissociate the functional roles of NCAM in the adult brain from developmental abnormalities, we generated a mutant in which the NCAM gene is inactivated by cre-recombinase under the control of the calcium-calmodulin-dependent kinase II promoter, resulting in reduction of NCAM expression predominantly in the hippocampus. This mutant (NCAMff+) did not show the overt morphological and behavioral abnormalities previously observed in constitutive NCAM-deficient (NCAM-/-) mice. However, similar to the NCAM-/- mouse, a reduction in long-term potentiation (LTP) in the CA1 region of the hippocampus was revealed. Long-term depression was also abolished in NCAMff+ mice. The deficit in LTP could be rescued by elevation of extracellular Ca2+ concentrations from 1.5 or 2.0 to 2.5 mm, suggesting an involvement of NCAM in regulation of Ca2+-dependent signaling during LTP. Contrary to the NCAM-/- mouse, LTP in the CA3 region was normal, consistent with normal mossy fiber lamination in NCAMff+ as opposed to abnormal lamination in NCAM-/- mice. NCAMff+ mutants did not show general deficits in short- and long-term memory in global landmark navigation in the water maze but were delayed in the acquisition of precise spatial orientation, a deficit that could be overcome by training. Thus, mice conditionally deficient in hippocampal NCAM expression in the adult share certain abnormalities characteristic of NCAM-/- mice, highlighting the role of NCAM in the regulation of synaptic plasticity in the CA1 region.

  7. The NMDA receptor antagonist CPP suppresses long-term potentiation in the rat hippocampal-accumbens pathway in vivo.

    PubMed

    Feasey-Truger, K J; ten Bruggencate, G

    1994-08-01

    Excitation of afferent fibres originating in the ventral subiculum of the hippocampus through stimulation of the fimbria elicits field potentials in the nucleus accumbens. When recorded in the dorsomedial aspect of the nucleus accumbens, the evoked field responses consisted of an early, negative-going component (N1) with a peak latency of 8-10 ms, followed by a second negative-going peak (N2) with a latency of 22-24 ms. The N1 response reflects monosynaptic activation of nucleus accumbens neurons; the N2 component appears to be polysynaptic in origin. In control rats, high-frequency stimulation of the fimbria (three trains at 250 Hz, 250 ms, delivered at 50 min intervals) resulted in a long-lasting potentiation of both the N1 and N2 components. The magnitude of potentiation exhibited by the polysynaptic N2 response was typically greater than that of the monosynaptically evoked N1 response. Following delivery of the first train, the amplitude of the N1 and N2 components was increased by approximately 20 and 50% respectively. Administration of the competitive N-methyl-D-aspartate (NMDA) receptor antagonist 3-[(+-)-2-carboxypiperazin-4-yl]-propyl-1-phosphonic acid (CPP, 10 mg/kg i.p.) had no significant effects on the evoked nucleus accumbens responses. High-frequency stimulation failed to produce a significant increase in the amplitude of either the N1 or the N2 response when delivered 45-60 min after CPP administration. To test whether the suppressant effects of CPP were time-dependent, two further high-frequency trains were applied 90 and 180 min after administration of the drug.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:7981867

  8. Long Term Sugarcane Crop Residue Retention Offers Limited Potential to Reduce Nitrogen Fertilizer Rates in Australian Wet Tropical Environments

    PubMed Central

    Meier, Elizabeth A.; Thorburn, Peter J.

    2016-01-01

    The warming of world climate systems is driving interest in the mitigation of greenhouse gas (GHG) emissions. In the agricultural sector, practices that mitigate GHG emissions include those that (1) reduce emissions [e.g., those that reduce nitrous oxide (N2O) emissions by avoiding excess nitrogen (N) fertilizer application], and (2) increase soil organic carbon (SOC) stocks (e.g., by retaining instead of burning crop residues). Sugarcane is a globally important crop that can have substantial inputs of N fertilizer and which produces large amounts of crop residues (‘trash’). Management of N fertilizer and trash affects soil carbon and nitrogen cycling, and hence GHG emissions. Trash has historically been burned at harvest, but increasingly is being retained on the soil surface as a ‘trash blanket’ in many countries. The potential for trash retention to alter N fertilizer requirements and sequester SOC was investigated in this study. The APSIM model was calibrated with data from field and laboratory studies of trash decomposition in the wet tropics of northern Australia. APSIM was then validated against four independent data sets, before simulating location × soil × fertilizer × trash management scenarios. Soil carbon increased in trash blanketed soils relative to SOC in soils with burnt trash. However, further increases in SOC for the study region may be limited because the SOC in trash blanketed soils could be approaching equilibrium; future GHG mitigation efforts in this region should therefore focus on N fertilizer management. Simulated N fertilizer rates were able to be reduced from conventional rates regardless of trash management, because of low yield potential in the wet tropics. For crops subjected to continuous trash blanketing, there was substantial immobilization of N in decomposing trash so conventional N fertilizer rates were required for up to 24 years after trash blanketing commenced. After this period, there was potential to reduce N

  9. Long Term Sugarcane Crop Residue Retention Offers Limited Potential to Reduce Nitrogen Fertilizer Rates in Australian Wet Tropical Environments.

    PubMed

    Meier, Elizabeth A; Thorburn, Peter J

    2016-01-01

    The warming of world climate systems is driving interest in the mitigation of greenhouse gas (GHG) emissions. In the agricultural sector, practices that mitigate GHG emissions include those that (1) reduce emissions [e.g., those that reduce nitrous oxide (N2O) emissions by avoiding excess nitrogen (N) fertilizer application], and (2) increase soil organic carbon (SOC) stocks (e.g., by retaining instead of burning crop residues). Sugarcane is a globally important crop that can have substantial inputs of N fertilizer and which produces large amounts of crop residues ('trash'). Management of N fertilizer and trash affects soil carbon and nitrogen cycling, and hence GHG emissions. Trash has historically been burned at harvest, but increasingly is being retained on the soil surface as a 'trash blanket' in many countries. The potential for trash retention to alter N fertilizer requirements and sequester SOC was investigated in this study. The APSIM model was calibrated with data from field and laboratory studies of trash decomposition in the wet tropics of northern Australia. APSIM was then validated against four independent data sets, before simulating location × soil × fertilizer × trash management scenarios. Soil carbon increased in trash blanketed soils relative to SOC in soils with burnt trash. However, further increases in SOC for the study region may be limited because the SOC in trash blanketed soils could be approaching equilibrium; future GHG mitigation efforts in this region should therefore focus on N fertilizer management. Simulated N fertilizer rates were able to be reduced from conventional rates regardless of trash management, because of low yield potential in the wet tropics. For crops subjected to continuous trash blanketing, there was substantial immobilization of N in decomposing trash so conventional N fertilizer rates were required for up to 24 years after trash blanketing commenced. After this period, there was potential to reduce N fertilizer

  10. Long Term Sugarcane Crop Residue Retention Offers Limited Potential to Reduce Nitrogen Fertilizer Rates in Australian Wet Tropical Environments.

    PubMed

    Meier, Elizabeth A; Thorburn, Peter J

    2016-01-01

    The warming of world climate systems is driving interest in the mitigation of greenhouse gas (GHG) emissions. In the agricultural sector, practices that mitigate GHG emissions include those that (1) reduce emissions [e.g., those that reduce nitrous oxide (N2O) emissions by avoiding excess nitrogen (N) fertilizer application], and (2) increase soil organic carbon (SOC) stocks (e.g., by retaining instead of burning crop residues). Sugarcane is a globally important crop that can have substantial inputs of N fertilizer and which produces large amounts of crop residues ('trash'). Management of N fertilizer and trash affects soil carbon and nitrogen cycling, and hence GHG emissions. Trash has historically been burned at harvest, but increasingly is being retained on the soil surface as a 'trash blanket' in many countries. The potential for trash retention to alter N fertilizer requirements and sequester SOC was investigated in this study. The APSIM model was calibrated with data from field and laboratory studies of trash decomposition in the wet tropics of northern Australia. APSIM was then validated against four independent data sets, before simulating location × soil × fertilizer × trash management scenarios. Soil carbon increased in trash blanketed soils relative to SOC in soils with burnt trash. However, further increases in SOC for the study region may be limited because the SOC in trash blanketed soils could be approaching equilibrium; future GHG mitigation efforts in this region should therefore focus on N fertilizer management. Simulated N fertilizer rates were able to be reduced from conventional rates regardless of trash management, because of low yield potential in the wet tropics. For crops subjected to continuous trash blanketing, there was substantial immobilization of N in decomposing trash so conventional N fertilizer rates were required for up to 24 years after trash blanketing commenced. After this period, there was potential to reduce N fertilizer

  11. Premature loss of primary anterior teeth due to trauma--potential short- and long-term sequelae.

    PubMed

    Holan, Gideon; Needleman, Howard L

    2014-04-01

    Traumatic dental injuries (TDIs) can result in the premature loss of primary anterior teeth due to an immediate avulsion, extraction later after the injury because of poor prognosis or late complications, or early exfoliation. There are a number of potential considerations or sequelae as a result of this premature loss that have been cited in the dental literature, which include esthetics, quality of life, eating, speech development, arch integrity (space loss), development and eruption of the permanent successors, and development of oral habits. This article provides a comprehensive review of the dental literature on the possible consequences of premature loss of maxillary primary incisors following TDI.

  12. Long-term assessment of the self-purification potential of a technologically managed ecosystem: the Middle Iskar cascade

    PubMed Central

    Lincheva, Stilyana; Todorova, Yovana; Topalova, Yana

    2014-01-01

    The Middle Iskar cascade is situated along the middle course of the Iskar River (Bulgaria) after the capital city Sofia and has three small hydroelectric power plants that were put into operation by the end of 2012. The aim of this study was to evaluate the self-purification potential of water in the reservoirs of these plants as an important and necessary condition for their ecological functioning. The assessment was made by hydrochemical parameters (dissolved suspended solids, insoluble suspended solids, total suspended solids, nitrites, nitrates, ammonium, phosphates, chemical oxygen demand, dissolved oxygen) and microbiological parameters (aerobic heterotrophic bacteria and bacteria growing in an Endo medium) and covered a period of three years (2010, 2011 and 2012). Standard methods were applied, mainly colorimetric and microbiological cultivation methods. The obtained results showed high levels of some of the tested indicators during 2012. In the section of the Middle Iskar cascade a high self-purification potential was observed in the reservoirs which maintain good water quality. PMID:26019531

  13. A greener Greenland? Climatic potential and long-term constraints on future expansions of trees and shrubs

    PubMed Central

    Normand, Signe; Randin, Christophe; Ohlemüller, Ralf; Bay, Christian; Høye, Toke T.; Kjær, Erik D.; Körner, Christian; Lischke, Heike; Maiorano, Luigi; Paulsen, Jens; Pearman, Peter B.; Psomas, Achilleas; Treier, Urs A.; Zimmermann, Niklaus E.; Svenning, Jens-Christian

    2013-01-01

    Warming-induced expansion of trees and shrubs into tundra vegetation will strongly impact Arctic ecosystems. Today, a small subset of the boreal woody flora found during certain Plio-Pleistocene warm periods inhabits Greenland. Whether the twenty-first century warming will induce a re-colonization of a rich woody flora depends on the roles of climate and migration limitations in shaping species ranges. Using potential treeline and climatic niche modelling, we project shifts in areas climatically suitable for tree growth and 56 Greenlandic, North American and European tree and shrub species from the Last Glacial Maximum through the present and into the future. In combination with observed tree plantings, our modelling highlights that a majority of the non-native species find climatically suitable conditions in certain parts of Greenland today, even in areas harbouring no native trees. Analyses of analogous climates indicate that these conditions are widespread outside Greenland, thus increasing the likelihood of woody invasions. Nonetheless, we find a substantial migration lag for Greenland's current and future woody flora. In conclusion, the projected climatic scope for future expansions is strongly limited by dispersal, soil development and other disequilibrium dynamics, with plantings and unintentional seed dispersal by humans having potentially large impacts on spread rates. PMID:23836785

  14. How the mechanisms of long-term synaptic potentiation and depression serve experience-dependent plasticity in primary visual cortex.

    PubMed

    Cooke, Sam F; Bear, Mark F

    2014-01-01

    Donald Hebb chose visual learning in primary visual cortex (V1) of the rodent to exemplify his theories of how the brain stores information through long-lasting homosynaptic plasticity. Here, we revisit V1 to consider roles for bidirectional 'Hebbian' plasticity in the modification of vision through experience. First, we discuss the consequences of monocular deprivation (MD) in the mouse, which have been studied by many laboratories over many years, and the evidence that synaptic depression of excitatory input from the thalamus is a primary contributor to the loss of visual cortical responsiveness to stimuli viewed through the deprived eye. Second, we describe a less studied, but no less interesting form of plasticity in the visual cortex known as stimulus-selective response potentiation (SRP). SRP results in increases in the response of V1 to a visual stimulus through repeated viewing and bears all the hallmarks of perceptual learning. We describe evidence implicating an important role for potentiation of thalamo-cortical synapses in SRP. In addition, we present new data indicating that there are some features of this form of plasticity that cannot be fully accounted for by such feed-forward Hebbian plasticity, suggesting contributions from intra-cortical circuit components. PMID:24298166

  15. Long-term use of biosolids as organic fertilizers in agricultural soils: potentially toxic elements occurrence and mobility.

    PubMed

    Marguí, E; Iglesias, M; Camps, F; Sala, L; Hidalgo, M

    2016-03-01

    The presence of potentially toxic elements (PTEs) may hinder a more widespread application of biosolids in agriculture. At present, the European Directive 86/278/CEE limit the total concentrations of seven metals (Cu, Cr, Ni, Pb, Zn, Cd and Hg) in agricultural soils and in sewage sludges used as fertilizers but it has not taken into consideration the potential impacts of other emerging micropollutants that may be present in the biosolids as well as their mobility. The aim of this study was to evaluate the accumulation and mobility of 13 elements (including regulated metals and other inorganic species) in agricultural soils repeatedly amended with biosolids for 15 years. Firstly, three digestions programs using different acid mixtures were tested to evaluate the most accurate and efficient method for analysis of soil and sludge. Results demonstrated that sewage sludge application increased concentrations of Pb and Hg in soil, but values did not exceed the quality standard established by legislation. In addition, other elements (As, Co, Sb, Ag, Se and Mn) that at present are not regulated by the Spanish and European directives were identified in the sewage sludge, and significant differences were found between Ag content in soils amended with biosolids in comparison with control soils. This fact can be related to the increasing use of silver nanoparticles in consumer products due to their antibacterial properties. Results from the leaching tests show up that, in general, the mobility degree for both regulated and non-regulated elements in soils amended with biosolids was quite low (<10 %).

  16. [Biographical work in inpatient long-term care for people with dementia: potential of the DEMIAN nursing concept].

    PubMed

    Berendonk, C; Stanek, S; Schönit, M; Kaspar, R; Bär, M; Kruse, A

    2011-02-01

    In nursing care for people with dementia, biographical work is a popular concept. In the literature and practice, many different viewpoints of the way biographical work can/should be promoted exist. In the DEMIAN concept, a nursing concept to promote emotional well-being for people with dementia, it is also of major significance. This article gives an overview of the importance of biographical work in caring for people with dementia. In particular, the role and arrangement of biographical work in the DEMIAN concept are described. Within the anamnesis of the DEMIAN concept, meaningful themes are identified in conversations with different participants (person with dementia, reference persons, and care workers) and through observations. From these findings, specific interventions, aimed at supporting emotional well-being of people with dementia, are derived and integrated into everyday nursing care to promote emotional well-being. The potential of the DEMIAN nursing concept are discussed and further possibilities are highlighted.

  17. Parkin overexpression ameliorates hippocampal long-term potentiation and β-amyloid load in an Alzheimer's disease mouse model.

    PubMed

    Hong, Xiaoqi; Liu, Jie; Zhu, Guoqi; Zhuang, YingHan; Suo, Haiyun; Wang, Pan; Huang, Dongping; Xu, Jing; Huang, Yufang; Yu, Mei; Bian, MinJuan; Sheng, Zhejin; Fei, Jian; Song, Houyan; Behnisch, Thomas; Huang, Fang

    2014-02-15

    Alzheimer's disease (AD) is a progressive neurodegenerative disorder characterized by a severe decline of memory performance. A widely studied AD mouse model is the APPswe/PSEN1ΔE9 (APP/PS1) strain, as mice exhibit amyloid plaques as well as impaired memory capacities. To test whether restoring synaptic plasticity and decreasing β-amyloid load by Parkin could represent a potential therapeutic target for AD, we crossed APP/PS1 transgenic mice with transgenic mice overexpressing the ubiquitin ligase Parkin and analyzed offspring properties. Overexpression of Parkin in APP/PS1 transgenic mice restored activity-dependent synaptic plasticity and rescued behavioral abnormalities. Moreover, overexpression of Parkin was associated with down-regulation of APP protein expression, decreased β-amyloid load and reduced inflammation. Our data suggest that Parkin could be a promising target for AD therapy.

  18. [Biographical work in inpatient long-term care for people with dementia: potential of the DEMIAN nursing concept].

    PubMed

    Berendonk, C; Stanek, S; Schönit, M; Kaspar, R; Bär, M; Kruse, A

    2011-02-01

    In nursing care for people with dementia, biographical work is a popular concept. In the literature and practice, many different viewpoints of the way biographical work can/should be promoted exist. In the DEMIAN concept, a nursing concept to promote emotional well-being for people with dementia, it is also of major significance. This article gives an overview of the importance of biographical work in caring for people with dementia. In particular, the role and arrangement of biographical work in the DEMIAN concept are described. Within the anamnesis of the DEMIAN concept, meaningful themes are identified in conversations with different participants (person with dementia, reference persons, and care workers) and through observations. From these findings, specific interventions, aimed at supporting emotional well-being of people with dementia, are derived and integrated into everyday nursing care to promote emotional well-being. The potential of the DEMIAN nursing concept are discussed and further possibilities are highlighted. PMID:21359631

  19. Long-term use of biosolids as organic fertilizers in agricultural soils: potentially toxic elements occurrence and mobility.

    PubMed

    Marguí, E; Iglesias, M; Camps, F; Sala, L; Hidalgo, M

    2016-03-01

    The presence of potentially toxic elements (PTEs) may hinder a more widespread application of biosolids in agriculture. At present, the European Directive 86/278/CEE limit the total concentrations of seven metals (Cu, Cr, Ni, Pb, Zn, Cd and Hg) in agricultural soils and in sewage sludges used as fertilizers but it has not taken into consideration the potential impacts of other emerging micropollutants that may be present in the biosolids as well as their mobility. The aim of this study was to evaluate the accumulation and mobility of 13 elements (including regulated metals and other inorganic species) in agricultural soils repeatedly amended with biosolids for 15 years. Firstly, three digestions programs using different acid mixtures were tested to evaluate the most accurate and efficient method for analysis of soil and sludge. Results demonstrated that sewage sludge application increased concentrations of Pb and Hg in soil, but values did not exceed the quality standard established by legislation. In addition, other elements (As, Co, Sb, Ag, Se and Mn) that at present are not regulated by the Spanish and European directives were identified in the sewage sludge, and significant differences were found between Ag content in soils amended with biosolids in comparison with control soils. This fact can be related to the increasing use of silver nanoparticles in consumer products due to their antibacterial properties. Results from the leaching tests show up that, in general, the mobility degree for both regulated and non-regulated elements in soils amended with biosolids was quite low (<10 %). PMID:26507732

  20. Predicting the effects of human developments on individual dolphins to understand potential long-term population consequences.

    PubMed

    Pirotta, Enrico; Harwood, John; Thompson, Paul M; New, Leslie; Cheney, Barbara; Arso, Monica; Hammond, Philip S; Donovan, Carl; Lusseau, David

    2015-11-01

    Human activities that impact wildlife do not necessarily remove individuals from populations. They may also change individual behaviour in ways that have sublethal effects. This has driven interest in developing analytical tools that predict the population consequences of short-term behavioural responses. In this study, we incorporate empirical information on the ecology of a population of bottlenose dolphins into an individual-based model that predicts how individuals' behavioural dynamics arise from their underlying motivational states, as well as their interaction with boat traffic and dredging activities. We simulate the potential effects of proposed coastal developments on this population and predict that the operational phase may affect animals' motivational states. For such results to be relevant for management, the effects on individuals' vital rates also need to be quantified. We investigate whether the relationship between an individual's exposure and the survival of its calves can be directly estimated using a Bayesian multi-stage model for calf survival. The results suggest that any effect on calf survival is probably small and that a significant relationship could only be detected in large, closely studied populations. Our work can be used to guide management decisions, accelerate the consenting process for coastal and offshore developments and design targeted monitoring. PMID:26511044

  1. Preliminary Assessment of Potential Habitat Composites' Durability when Exposed to a Long-Term Radiation Environment and Micrometeoroid Impacts

    NASA Technical Reports Server (NTRS)

    Rojdev, Kristina; Graves, Russell; Golden, John; Atwell, William; O'Rouke, Mary Jane; Hill, Charles; Alred, John

    2011-01-01

    NASA's exploration goals include extending human presence beyond low earth orbit (LEO). As a result, habitation for crew is a critical requirement for meeting this goal. However, habitats are very large structures that contain a multitude of subsystems to sustain human life over long-durations in space, and one of the key challenges has been keeping weight to a minimum in order to reduce costs. Thus, light-weight and multifunctional structural materials are of great interest for habitation. NASA has started studying polymeric composite materials as potential lightweight and multifunctional structural materials for use in long-duration spaceflight. However, little is known about the survivability of these materials when exposed to the space environment outside of LEO for long durations. Thus, a study has been undertaken to investigate the durability of composite materials when exposed to long-duration radiation. Furthermore, as an addition to the primary study, a secondary preliminary investigation has been started on the micrometeoroid and orbital debris (MMOD) susceptibility of these materials after radiation exposure. The combined effects of radiation and MMOD impacts are the focus of this paper.

  2. Potential for long-term transfer of dissolved organic carbon from riparian zones to streams in boreal catchments.

    PubMed

    Ledesma, José L J; Grabs, Thomas; Bishop, Kevin H; Schiff, Sherry L; Köhler, Stephan J

    2015-08-01

    Boreal regions store most of the global terrestrial carbon, which can be transferred as dissolved organic carbon (DOC) to inland waters with implications for both aquatic ecology and carbon budgets. Headwater riparian zones (RZ) are important sources of DOC, and often just a narrow 'dominant source layer' (DSL) within the riparian profile is responsible for most of the DOC export. Two important questions arise: how long boreal RZ could sustain lateral DOC fluxes as the sole source of exported carbon and how its hydromorphological variability influences this role. We estimate theoretical turnover times by comparing carbon pools and lateral exports in the DSL of 13 riparian profiles distributed over a 69 km(2) catchment in northern Sweden. The thickness of the DSL was 36 ± 18 (average ± SD) cm. Thus, only about one-third of the 1-m-deep riparian profile contributed 90% of the lateral DOC flux. The 13 RZ exported 8.7 ± 6.5 g C m(-2) year(-1) , covering the whole range of boreal stream DOC exports. The variation could be explained by local hydromorphological characteristics including RZ width (R(2) = 0.90). The estimated theoretical turnover times were hundreds to a few thousands of years, that is there is a potential long-lasting supply of DOC. Estimates of net ecosystem production in the RZ suggest that lateral fluxes, including both organic and inorganic C, could be maintained without drawing down the riparian pools. This was supported by measurements of stream DO(14) C that indicated modern carbon as the predominant fraction exported, including streams disturbed by ditching. The transfer of DOC into boreal inland waters from new and old carbon sources has a major influence on surface water quality and global carbon balances. This study highlights the importance of local variations in RZ hydromorphology and DSL extent for future DOC fluxes under a changing climate.

  3. Japan's Long-term Energy Demand and Supply Scenario to 2050 - Estimation for the Potential of Massive CO2 Mitigation

    SciTech Connect

    Komiyama, Ryoichi; Marnay, Chris; Stadler, Michael; Lai, Judy; Borgeson, Sam; Coffey, Brian; Azevedo, Ines Lima

    2009-09-01

    In this analysis, the authors projected Japan's energy demand/supply and energy-related CO{sub 2} emissions to 2050. Their analysis of various scenarios indicated that Japan's CO{sub 2} emissions in 2050 could be potentially reduced by 26-58% from the current level (FY 2005). These results suggest that Japan could set a CO{sub 2} emission reduction target for 2050 at between 30% and 60%. In order to reduce CO{sub 2} emissions by 60% in 2050 from the present level, Japan will have to strongly promote energy conservation at the same pace as an annual rate of 1.9% after the oil crises (to cut primary energy demand per GDP (TPES/GDP) in 2050 by 60% from 2005) and expand the share of non-fossil energy sources in total primary energy supply in 2050 to 50% (to reduce CO{sub 2} emissions per primary energy demand (CO{sub 2}/TPES) in 2050 by 40% from 2005). Concerning power generation mix in 2050, nuclear power will account for 60%, solar and other renewable energy sources for 20%, hydro power for 10% and fossil-fired generation for 10%, indicating substantial shift away from fossil fuel in electric power supply. Among the mitigation measures in the case of reducing CO{sub 2} emissions by 60% in 2050, energy conservation will make the greatest contribution to the emission reduction, being followed by solar power, nuclear power and other renewable energy sources. In order to realize this massive CO{sub 2} abatement, however, Japan will have to overcome technological and economic challenges including the large-scale deployment of nuclear power and renewable technologies.

  4. Juvenile flatfish in the northern Baltic Sea - long-term decline and potential links to habitat characteristics

    NASA Astrophysics Data System (ADS)

    Jokinen, Henri; Wennhage, Håkan; Ollus, Victoria; Aro, Eero; Norkko, Alf

    2016-01-01

    Flatfish in the northern Baltic Sea are facing multiple environmental pressures due to on-going large-scale ecosystem changes linked to eutrophication and climate change. Shallow juvenile habitats of flatfishes are expected to be especially susceptible to these environmental pressures. Using previously unpublished historical and present-state data on juvenile flatfish in nursery areas along the Finnish coast we demonstrate a drastic (up to 40 ×) decline in 1-Y-O flounder densities since the 1980s and a particularly low current occurrence of both flounders and turbots in several known juvenile habitats. As a consequence of ongoing coastal eutrophication vegetation coverage and filamentous algae have generally increased in shallow areas. We examined the predicted negative effect of vegetation/algae by exploring quantitative relationships between juvenile flatfish (flounder and turbot) occurrence and vegetation/algae among other environmental factors in shallow juvenile habitats. Despite sparse occurrence of juveniles we found a significant negative relationship between flatfish abundance and vegetation cover, implicating eutrophication as a potential major driver affecting the value of juvenile habitat. Shallow littoral habitats play a particularly central role for flatfish due to the spatial concentration of fish in these areas during the critical juvenile stage. Despite their importance, these areas have been relatively poorly studied in the northern Baltic Sea, which makes it difficult to quantify overall changes in environmental conditions and to relate these changes to flatfish recruitment. The low present-state flatfish densities recorded preclude strong inferences of the role of habitat quality to be drawn. Our study does, however, provide a baseline for future assessment. Based on existing evidence, we cannot thus establish any bottlenecks but hypothesize that the current low occurrence of juvenile flatfish, and the population decline of flounder on the

  5. Acute and long-term behavioral correlates of underwater trauma--potential relevance to stress and post-stress syndromes.

    PubMed

    Richter-Levin, G

    1998-06-01

    As a consequence of a brief but significantly extreme stressor, an individual will experience a stress response, which may sometimes develop into Acute Stress Disorder (ASD) or Post-Traumatic Stress Disorder (PTSD). Though a rat model for ASD and PTSD is not expected to encompass the richness and complexity of the disorders in humans, it will enable the study of the common underlying mechanisms that generate the disorders, the study of pre-trauma etiological aspects of the disorders and the screening of drugs with potential relevance to the treatment of the disorders. One well-documented aspect of PTSD is the enhancing influence of contextual elements on the appearance of symptoms of the post-stress trauma. To exploit this effect, we have chosen to assess the effects of an underwater trauma in the Morris water maze since the effects of such trauma on memory and attention can be later evaluated in the context of the trauma. At both 1 h and 3 weeks after the trauma, significant behavioral deficits were observed in the water maze. The effects of the underwater trauma on the performance of rats in the water maze were context specific. Underwater trauma in a different (out-of-context) water container had no effects on the ability of rats to perform a spatial memory task in the water maze. An elevated level of anxiety was found in the plus maze test, independently of whether the trauma was performed in the water maze or in a different (out-of-context) water container. The results indicate that a within-context underwater trauma has both acute and lasting behavioral consequences which can be assessed using a spatial memory test in the context of the trauma. The results are discussed in relation to their relevance to stress and PTSD.

  6. Methamphetamine-induced enhancement of hippocampal long-term potentiation is modulated by NMDA and GABA receptors in the shell-accumbens.

    PubMed

    Heysieattalab, Soomaayeh; Naghdi, Nasser; Hosseinmardi, Narges; Zarrindast, Mohammad-Reza; Haghparast, Abbas; Khoshbouei, Habibeh

    2016-08-01

    Addictive drugs modulate synaptic transmission in the meso-corticolimbic system by hijacking normal adaptive forms of experience-dependent synaptic plasticity. Psychostimulants such as METH have been shown to affect hippocampal synaptic plasticity, albeit with a less understood synaptic mechanism. METH is one of the most addictive drugs that elicit long-term alterations in the synaptic plasticity in brain areas involved in reinforcement learning and reward processing. Dopamine transporter (DAT) is one of the main targets of METH. As a substrate for DAT, METH decreases dopamine uptake and increases dopamine efflux via the transporter in the target brain regions such as nucleus accumbens (NAc) and hippocampus. Due to cross talk between NAc and hippocampus, stimulation of NAc has been shown to alter hippocampal plasticity. In this study, we tested the hypothesis that manipulation of glutamatergic and GABA-ergic systems in the shell-NAc modulates METH-induced enhancement of long term potentiation (LTP) in the hippocampus. Rats treated with METH (four injections of 5 mg/kg) exhibited enhanced LTP as compared to saline-treated animals. Intra-NAc infusion of muscimol (GABA receptor agonist) decreased METH-induced enhancement of dentate gyrus (DG)-LTP, while infusion of AP5 (NMDA receptor antagonist) prevented METH-induced enhancement of LTP. These data support the interpretation that reducing NAc activity can ameliorate METH-induced hippocampal LTP through a hippocampus-NAc-VTA circuit loop. Synapse 70:325-335, 2016. © 2016 Wiley Periodicals, Inc. PMID:27029021

  7. The effect of long-term Cd and Ni exposure on seed endophytes of Agrostis capillaris and their potential application in phytoremediation of metal-contaminated soils.

    PubMed

    Truyens, S; Jambon, I; Croes, S; Janssen, J; Weyens, N; Mench, M; Carleer, R; Cuypers, A; Vangronsveld, J

    2014-01-01

    We examined whether long-term Cd exposure leads to beneficial changes in the cultivable endophytic bacteria present in the seeds of Agrostis capillaris. Therefore the cultivable seed endophytes of Agrostis capillaris growing on a long-term Cd/Ni-contaminated plot (Cd/Ni seeds) were compared with those originating from a non-contaminated plot (control seeds). We observed plant- and contaminant-dependent effects on the population composition between control and Cd/Ni seeds. Also differences in phenotypic characteristics were found: endophytes from Cd/Ni seeds exhibited more ACC deaminase activity and production of siderophores and IAA, while endophytes from control seeds, very surprisingly, showed more metal tolerance. Finally, the 3 most promising seed endophytes were selected based on their metal tolerance and plant growth promoting potential, and inoculated in Agrostis capillaris seedlings. In case of non-exposed plants, inoculation resulted in a significantly improved plant growth; after inoculation of Cd-exposed plants an increased Cd uptake was achieved without affecting plant growth. This indicates that inoculation of Agrostis with its seed endophytes might be beneficial for its establishment during phytoextraction and phytostabilisation of Cd-contaminated soils.

  8. Long-term operation of biological activated carbon pre-treatment for microfiltration of secondary effluent: Correlation between the organic foulants and fouling potential.

    PubMed

    Pramanik, Biplob Kumar; Roddick, Felicity A; Fan, Linhua

    2016-03-01

    The impact of long-term (>2 years) biological activated carbon (BAC) treatment for mitigating organic fouling in the microfiltration of biologically treated secondary effluent was investigated. Correlation between the organic constituents and hydraulic filtration resistance was investigated to identify the major components responsible for fouling. Over two years operation, the removal efficiency for dissolved organic carbon (DOC) by the BAC treatment was fairly consistent (30 ± 3%), although the reduction in UVA254 gradually decreased from 56 to 34%. BAC treatment effectively decreased the organic foulants in the effluent and so contributed to the mitigation of membrane fouling as shown by reduction in the unified membrane fouling index (UMFI). BAC consistently removed biopolymers whereas the removal of humic substances decreased from 52 to 25% after two years of BAC operation, and thus led to a gradual decrease in UMFI reduction efficiency from 78 to 43%. This was due to gradual reduction in adsorption capacity of the activated carbon as confirmed by analysis of its pore size distribution. Hence humics also played an important role in membrane fouling. However, there was a good correlation between protein and carbohydrate contents with hydraulically reversible and irreversible filtration resistance, compared with UVA254, turbidity and DOC. Although the mitigation of membrane fouling decreased over time, this study demonstrated that the long-term use of BAC pre-treatment of biologically treated secondary effluent prior to microfiltration has potential to reduce the need for frequent chemical cleaning and so increase membrane life span.

  9. Calcitonin gene-related peptide erases the fear memory and facilitates long-term potentiation in the central nucleus of the amygdala in rats.

    PubMed

    Wu, Xin; Zhang, Jie-Ting; Liu, Jue; Yang, Si; Chen, Tao; Chen, Jian-Guo; Wang, Fang

    2015-11-01

    Calcitonin gene-related peptide (CGRP) is a 37 amino acid neuropeptide, which plays a critical role in the central nervous system. CGRP binds to G protein-coupled receptors, including CGRP1, which couples positively to adenylyl cyclase (AC) and protein kinase A (PKA) activation. CGRP and CGRP1 receptors are enriched in central nucleus of the amygdala (CeA), the main part of the amygdala, which regulates conditioned fear memories. Here, we reported the importance of CGRP and CGRP1 receptor for synaptic plasticity in the CeA and the extinction of fear memory in rats. Our electrophysiological and behavioral in vitro and in vivo results showed exogenous application of CGRP induced an immediate and lasting long-term potentiation in the basolateral nucleus of amygdala-CeA pathway, but not in the lateral nucleus of amygdala-CeA pathway, while bilateral intra-CeA infusion CGRP (0, 5, 13 and 21 μM/side) dose dependently enhanced fear memory extinction. The effects were blocked by CGRP1 receptor antagonist (CGRP8-37 ), N-methyl-d-aspartate receptors antagonist MK801 and PKA inhibitor H89. These results demonstrate that CGRP can lead to long-term potentiation of basolateral nucleus of amygdala-CeA pathway through a PKA-dependent postsynaptic mechanism that involved N-methyl-d-aspartate receptors and enhance the extinction of fear memory in rats. Together, the results strongly support a pivotal role of CGRP in the synaptic plasticity of CeA and extinction of fear memory. Calcitonin gene-related peptide (CGRP) plays an essential role in synaptic plasticity in the amygdala and fear memory. We found that CGRP-induced chemical long-term potentiation (LTP) in a dose-dependent way in the BLA-CeA (basolateral and central nucleus of amygdala, respectively) pathway and enhanced fear memory extinction in rats through a protein kinase A (PKA)-dependent postsynaptic mechanism that involved NMDA receptors. These results support a pivotal role of CGRP in amygdala.

  10. Long-term low-dose α-particle enhanced the potential of malignant transformation in human bronchial epithelial cells through MAPK/Akt pathway

    SciTech Connect

    Liu, Weili; Xiao, Linlin; Dong, Chen; He, Mingyuan; Pan, Yan; Xie, Yuexia; Tu, Wenzhi; Fu, Jiamei; Shao, Chunlin

    2014-05-09

    Highlights: • Multi-exposures of 25 mGy α-ray enhanced cell proliferation, adhesion, and invasion. • MAPK/Akt but not JNK/P66 was positively correlated with cell invasive phenotypes. • LDR of α-irradiation triggers cell malignant transformation through MAPK/Akt. - Abstract: Since the wide usage of ionizing radiation, the cancer risk of low dose radiation (LDR) (<0.1 Gy) has become attractive for a long time. However, most results are derived from epidemiologic studies on atomic-bomb survivors and nuclear accidents surrounding population, and the molecular mechanism of this risk is elusive. To explore the potential of a long-term LDR-induced malignant transformation, human bronchial epithelial cells Beas-2B were fractionally irradiated with 0.025 Gy α-particles for 8 times in total and then further cultured for 1–2 months. It was found that the cell proliferation, the abilities of adhesion and invasion, and the protein expressions of p-ERK, p-Akt, especially p-P38 were not only increased in the multiply-irradiated cells but also in their offspring 1–2 months after the final exposure, indicating high potentiality of cell malignant transformation. On opposite, the expressions of p-JNK and p-P66 were diminished in the subcultures of irradiated cells and thus may play a role of negative regulation in canceration. When the cells were transferred with p38 siRNA, the LDR-induced enhancements of cell adhesion and invasion were significantly reduced. These findings suggest that long-term LDR of α-particles could enhance the potential of malignant transformation incidence in human bronchial epithelial cells through MAPK/Akt pathway.

  11. Testicular hormones do not regulate sexually dimorphic Pavlovian fear conditioning or perforant-path long-term potentiation in adult male rats.

    PubMed

    Anagnostaras, S G; Maren, S; DeCola, J P; Lane, N I; Gale, G D; Schlinger, B A; Fanselow, M S

    1998-04-01

    We recently reported that Pavlovian fear conditioning and hippocampal perforant-path long-term potentiation (LTP) are sexually dimorphic in rats. Males show greater contextual fear conditioning, which depends on the hippocampus, as well as greater hippocampal LTP. In order to examine the role of circulating gonadal hormones in adult male rats, animals were castrated in two experiments, and Pavlovian fear conditioning and in vivo perforant-path LTP were examined. It was found that sexually-dimorphic LTP and fear conditioning are not regulated by the activational effects of testicular hormones in adult male rats. That is, in every respect, castrated male rats were similar to intact male rats in Pavlovian fear conditioning and hippocampal LTP. It is likely that sexual dimorphism in this system is established earlier in development by the organizational effects of gonadal hormones.

  12. Thrombin induces long-term potentiation of reactivity to afferent stimulation and facilitates epileptic seizures in rat hippocampal slices: toward understanding the functional consequences of cerebrovascular insults.

    PubMed

    Maggio, Nicola; Shavit, Efrat; Chapman, Joab; Segal, Menahem

    2008-01-16

    The effects of thrombin, a blood coagulation serine protease, were studied in rat hippocampal slices, in an attempt to comprehend its devastating effects when released into the brain after stroke and head trauma. Thrombin acting through its receptor, protease-activated receptor 1 (PAR1), produced a long-lasting enhancement of the reactivity of CA1 neurons to afferent stimulation, an effect that saturated the ability of the tissue to undergo tetanus-induced long-term potentiation. This effect was mediated by activation of a PAR1 receptor, because it was shared by a PAR1 agonist, and was blocked by its selective antagonist. An independent effect of thrombin involved the lowering of the threshold for generating epileptic seizures in CA3 region of the hippocampus. Thus, the experiments in a slice mimicked epileptic and cognitive dysfunction induced by thrombin in the brain, and suggest that these effects are mediated by activation of the PAR1 receptor. PMID:18199772

  13. Long-Term Potentiation at CA3–CA1 Hippocampal Synapses with Special Emphasis on Aging, Disease, and Stress

    PubMed Central

    Kumar, Ashok

    2011-01-01

    Synaptic plasticity in the mammalian central nervous system has been the subject of intense investigation for the past four decades. Long-term potentiation (LTP), a major reflection of synaptic plasticity, is an activity-driven long-lasting increase in the efficacy of excitatory synaptic transmission following the delivery of a brief, high-frequency train of electrical stimulation. LTP is regarded as a principal candidate for the cellular mechanisms involved in learning and offers an attractive hypothesis of how memories are constructed. There are a number of exceptional full-length reviews published on LTP; the current review intends to present an overview of the research findings regarding hippocampal LTP with special emphasis on aging, diseases, and psychological insults. PMID:21647396

  14. Acute stress causes rapid synaptic insertion of Ca2+ -permeable AMPA receptors to facilitate long-term potentiation in the hippocampus.

    PubMed

    Whitehead, Garry; Jo, Jihoon; Hogg, Ellen L; Piers, Thomas; Kim, Dong-Hyun; Seaton, Gillian; Seok, Heon; Bru-Mercier, Gilles; Son, Gi Hoon; Regan, Philip; Hildebrandt, Lars; Waite, Eleanor; Kim, Byeong-Chae; Kerrigan, Talitha L; Kim, Kyungjin; Whitcomb, Daniel J; Collingridge, Graham L; Lightman, Stafford L; Cho, Kwangwook

    2013-12-01

    The neuroendocrine response to episodes of acute stress is crucial for survival whereas the prolonged response to chronic stress can be detrimental. Learning and memory are particularly susceptible to stress with cognitive deficits being well characterized consequences of chronic stress. Although there is good evidence that acute stress can enhance cognitive performance, the mechanism(s) for this are unclear. We find that hippocampal slices, either prepared from rats following 30 min restraint stress or directly exposed to glucocorticoids, exhibit an N-methyl-d-aspartic acid receptor-independent form of long-term potentiation. We demonstrate that the mechanism involves an NMDA receptor and PKA-dependent insertion of Ca2+ -permeable AMPA receptors into synapses. These then trigger the additional NMDA receptor-independent form of LTP during high frequency stimulation.

  15. M2 muscarinic acetylcholine receptors regulate long-term potentiation at hippocampal CA3 pyramidal cell synapses in an input-specific fashion

    PubMed Central

    Zheng, Fang; Wess, Jürgen

    2012-01-01

    Muscarinic receptors have long been known as crucial players in hippocampus-dependent learning and memory, but our understanding of the cellular underpinnings and the receptor subtypes involved lags well behind. This holds in particular for the hippocampal CA3 region, where the mechanisms of synaptic plasticity depend on the type of afferent input. Williams and Johnston (Williams S, Johnston D. Science 242: 84–87, 1988; Williams S, Johnston D. J Neurophysiol 64: 1089–1097, 1990) demonstrated muscarinic depression of mossy fiber (MF) long-term potentiation (LTP) through a presynaptic site of action and Maeda et al. (Maeda T, Kaneko S, Satoh M. Brain Res 619: 324–330, 1993) proposed a bidirectional modulation of MF LTP by muscarinic receptor subtypes. Since then, this issue, as well as muscarinic regulation of plasticity at associational/commissural (A/C) fiber-CA3 synapses has remained largely neglected, not least because of the lack of highly selective ligands for the different muscarinic receptor subtypes. In the present study, we performed field potential and whole cell recordings from the hippocampal CA3 region of M2 receptor knockout mice to determine the role of M2 receptors in short-term and long-term plasticity at A/C and MF inputs to CA3 pyramidal cells. At the A/C synapse, M2 receptors promoted short-term facilitation and LTP. Unexpectedly, M2 receptors mediated the opposite effect on LTP at the MF synapse, which was significantly reduced, most likely involving a depressant effect of M2 receptors on adenylyl cyclase activity in MF terminals. Our data demonstrate that cholinergic projections recruit M2 receptors to redistribute the gain of LTP in CA3 pyramidal cells in an input-specific manner. PMID:22490561

  16. Observed and Potential Responses of Upland Tundra Ecosystems to a Changing Climate: Results from the Arctic Long-Term Ecological Research Project, North Slope, Alaska, USA

    NASA Astrophysics Data System (ADS)

    Bowden, W. B.

    2014-12-01

    The Arctic is one of the most rapidly changing biomes on earth. Research at the Toolik Field Station by the Arctic Long-Term Ecological Research project provides a perspective on changes that are impacting the upland tussock tundra region of the North Slope of Alaska, a region that is typical of ~15% of the arctic region. The arctic is responding to a combination of long-term, gradual changes (presses) and short-term, event-driven changes (pulses). The most important press, of course, is the persistent rise in average annual air temperature observed in most places (though not at Toolik). Associated with this increase in SAT is a well-documented increase in shallow permafrost temperature (which is observed around Toolik). Our long-term research shows that this trend will favor taller and more productive shrub and grass vegetation. Higher SAT translates to earlier spring breakup and later onset of winter. This change in seasonality is affecting interactions between shrub leaf-out, insect emergence, and bird nesting. Persistent and more frequent droughts are having important impacts on the ability of Arctic grayling - the top consumer is most upland tundra streams - to survive and has the potential to block their ability to migrate to essential overwintering lakes. The interaction between temperature (which is changing) and light (which is not) creates a "seasonal asynchrony" that may be increasing the loading of nutrients - notably nitrate - to upland tundra streams late in the season, with impacts that we do not fully understand yet. The upland tundra environment is also responding to an increasing frequency of pulses, most notably wildfires and the development of thermo-erosional failures (TEFs). Wildfires transfer large quantities of carbon and nitrogen directly to the atmosphere. TEFs may deliver large quantities of sediment and nutrients to streams and lakes. Currently these pulse disturbances seem to be having only limited, local impacts. However, as shallow

  17. Effects of Joint Attention on Long-Term Memory in 9-Month-Old Infants: An Event-Related Potentials Study

    ERIC Educational Resources Information Center

    Kopp, Franziska; Lindenberger, Ulman

    2011-01-01

    Joint attention develops during the first year of life but little is known about its effects on long-term memory. We investigated whether joint attention modulates long-term memory in 9-month-old infants. Infants were familiarized with visually presented objects in either of two conditions that differed in the degree of joint attention (high…

  18. Evaluation of a deposit in the vicinity of the PBU L-106 Site, North Slope, Alaska, for a potential long-term test of gas production from hydrates

    SciTech Connect

    Moridis, G.J.; Reagan, M.T.; Boyle, K.L.; Zhang, K.

    2010-05-01

    As part of the effort to investigate the technical feasibility of gas production from hydrate deposits, a long-term field test (lasting 18-24 months) is under consideration in a project led by the U.S. Department of Energy. We evaluate a candidate deposit involving the C-Unit in the vicinity of the PBU-L106 site in North Slope, Alaska. This deposit is stratigraphically bounded by impermeable shale top and bottom boundaries (Class 3), and is characterized by high intrinsic permeabilities, high porosity, high hydrate saturation, and a hydrostatic pressure distribution. The C-unit deposit is composed of two hydrate-bearing strata separated by a 30-ft-thick shale interlayer, and its temperatrure across its boundaries ranges between 5 and 6.5 C. We investigate by means of numerical simulation involving very fine grids the production potential of these two deposits using both vertical and horizontal wells. We also explore the sensitivity of production to key parameters such as the hydrate saturation, the formation permeability, and the permeability of the bounding shale layers. Finally, we compare the production performance of the C-Unit at the PBU-L106 site to that of the D-Unit accumulation at the Mount Elbert site, a thinner, single-layer Class 3 deposit on the North Slope of Alaska that is shallower, less-pressurized and colder (2.3-2.6 C). The results indicate that production from horizontal wells may be orders of magnitude larger than that from vertical ones. Additionally, production increases with the formation permeability, and with a decreasing permeability of the boundaries. The effect of the hydrate saturation on production is complex and depends on the time frame of production. Because of higher production, the PBU-L106 deposit appears to have an advantage as a candidate for the long-term test.

  19. Priming of long-term potentiation in mouse hippocampus by corticotropin-releasing factor and acute stress: implications for hippocampus-dependent learning.

    PubMed

    Blank, Thomas; Nijholt, Ingrid; Eckart, Klaus; Spiess, Joachim

    2002-05-01

    In the present experiments, we characterized the action of human/rat corticotropin-releasing factor (h/rCRF) and acute stress (1 hr of immobilization) on hippocampus-dependent learning and on synaptic plasticity in the mouse hippocampus. We first showed that h/rCRF application and acute stress facilitated (primed) long-term potentiation of population spikes (PS-LTP) in the mouse hippocampus and enhanced context-dependent fear conditioning. Both the priming of PS-LTP and the improvement of context-dependent fear conditioning were prevented by the CRF receptor antagonist [Glu(11,16)]astressin. PS-LTP priming and improved learning were also reduced by the protein kinase C inhibitor bisindolylmaleimide I. Acute stress induced the activation of Ca2+/calmodulin-dependent kinase II (CaMKII) 2 hr after the end of the stress session. The CaMKII inhibitor KN-62 antagonized the stress-mediated learning enhancement, however, with no effect on PS-LTP persistence. Thus, long-lasting increased neuronal excitability as reflected in PS-LTP priming appeared to be essential for the enhancement of learning in view of the observation that inhibition of PS-LTP priming was associated with impaired learning. Conversely, it was demonstrated that inhibition of CaMKII activity reduced contextual fear conditioning without affecting PS-LTP priming. This observation suggests that priming of PS-LTP and activation of CaMKII represent two essential mechanisms that may contribute independently to long-term memory.

  20. Arsenic downregulates gene expression at the postsynaptic density in mouse cerebellum, including genes responsible for long-term potentiation and depression.

    PubMed

    Zhang, Cong; Li, Sheng; Sun, Yahui; Dong, Wei; Piao, Fengyuan; Piao, Yongjun; Liu, Shuang; Guan, Huai; Yu, Shengbo

    2014-08-01

    Arsenic (As) is a neurotoxin induces dysfunction of learning and memory. Research has indicated that cerebellum may be involved in arsenic-induced impairment of learning and memory. However, the molecular mechanisms that underlie these effects remain unclear. This study screened for the differentially expressed genes related to the long-term potentiation and long-term depression (LTP and LTD) at the cerebellar postsynaptic density (PSD) of mice following exposure to arsenic, and we provide evidence of the mechanism by which arsenic adversely affects the functions of learning and memory. Here, SPF mice were exposed to 1ppm, 2ppm and 4ppm As2O3 for 60 days. The ultrastructure of the synapses in cerebella of these mice was observed via transmission electron microscopy. The cerebellum global gene expression of mice exposed to 4ppm As2O3 was determined through GeneChip analysis. We used the web tool DAVID to analyze the Gene Ontology (GO) and KEGG pathways that were significantly enriched among the differentially expressed genes. Our observations of synaptic ultrastructure showed that the thickness of the cerebellar PSD was reduced in mice exposed to arsenic. Go analysis revealed the PSD as a significantly altered cellular component. KEGG pathway analysis showed that LTP and LTD were affected by arsenic with highest statistical significance, and 20 differentially expressed genes were associated with them. Among these differentially expressed genes, significant decreases in the mRNA expressions of CaMKII, Gria1, Gria2, Grin1, Itpr1, Grm1 and PLCβ4 related to the LTP and LTD were found at the PSD of mouse cerebellum exposed to arsenic. The downregulation of these genes was further confirmed via real-time reverse transcription PCR or Western blot at 1ppm, 2ppm and 4ppm As2O3. Our results indicate that the 7 genes with in cerebellar PSDs may be involved in arsenic-induced neurotoxicity, including impairment of learning and memory.

  1. Nitrogen transformations in a Vertisol under long-term tillage and no tillage management in dryland agricultual systems: key genes and potential rates

    NASA Astrophysics Data System (ADS)

    Melero, Sebastiana; Perez de Mora, Alfredo; Murillo, J. Manuel; Buegger, Franz; Kleinedam, Kristina; Kublik, Susanne; Vanderlinden, Karl; Moreno, Felix; Schloter, Michael

    2010-05-01

    The impact of tillage practices on microbial N transformations in semiarid regions is poorly understood and data from long-term field experiments are scarce. In this study, we evaluated the effects of traditional tillage (TT) vs no-tillage (NT) on key processes of the N cycle such as nitrification and denitrification in a long-term field experiment under a rainfed crop rotation system (cereal-sunflower-legumes) on a vertisol (SW Spain). Besides general soil chemical and biological parameters, we quantified the size of the ammonia oxidizing and denitrifying bacterial populations via real-time PCR (amoA, nirS and nosZ genes), and measured potential nitrification and denitrification rates. Soil was sampled at two depths (0-30, till layer; and 30-50 cm), once during the growing period of the crop (wheat) and another time after harvesting. Conservation tillage slightly increased total organic carbon and microbial biomass C content, whereas no effect on nutrient availability (C and N) was observed, likely due to the fertilization regime and the textural characteristics of the soil type (Vertisol). Gene abundance and potential rates were influenced by the interaction between tillage treatment and sampling period, mainly at 0-30 cm depth. In general, ammonia oxidizers and potential nitrification were enhanced under TT, particularly after harvesting. By contrast, higher abundance of denitrifiers, as reflected by both nirS and nosZ gene copy numbers and larger potential denitrification rates were found under NT during the growing period, but not after harvesting. Results also showed that the N2O/N2 ratio was constant throughout the experiment and thus was affected more significantly by environmental parameters such as the availability carbon than by changes in denitrifier abundance. Our results stress the importance of quantifying microbial populations to address the impact of agricultural practices on N transformations in soil. Furthermore, results suggest that the spatial

  2. Short and long term bystander effect induction by fathead minnows (Pimephales promelas, Rafinesque, 1820) injected with environmentally relevant whole body doses of 226Ra.

    PubMed

    Smith, Richard W; Seymour, Colin B; Mothersill, Carmel E

    2013-12-01

    Bystander effect induction by fathead minnows injected with environmentally relevant doses of (226)Ra was investigated. Twenty four h and 6 months after injection with a single dose of 21, 210 or 2100 μBq, fin tissue samples emitted a pro-apoptotic signal, which reduced the clonogenic survival of an apoptosis sensitive reporter cell line. Twenty four h and 10 weeks after injection explants from non-injected bystander fish, swum with the injected fish, also emitted a pro-apoptotic signal. However 6 months after injection the bystander fish to 21 and 210 μBq injected fish emitted an anti-apoptotic signal. This demonstrates that extremely low dose irradiation can have effects outside of the irradiated fish. This has implications for population and ecosystem responses to contamination. PMID:23981564

  3. Invasive fungal diseases during first induction chemotherapy affect complete remission achievement and long-term survival of patients with acute myeloid leukemia.

    PubMed

    Girmenia, Corrado; Micozzi, Alessandra; Piciocchi, Alfonso; Gentile, Giuseppe; Di Caprio, Luigi; Nasso, Daniela; Minotti, Clara; Capria, Saveria; Cartoni, Claudio; Alimena, Giuliana; Meloni, Giovanna; Amadori, Sergio; Foà, Robin; Venditti, Adriano

    2014-04-01

    We retrospectively evaluated, in a logistic-regression-model, the role of proven/probable invasive fungal diseases (PP-IFD), occurring during first induction chemotherapy, on the achievement of complete remission (CR) and overall survival (OS) in 198 acute myeloid leukemia (AML) patients. A PP-IFD was documented in 34 (17.2%) patients. Younger age, good performance status at AML diagnosis and no development of a PP-IFD (OR 4.09, 95% CI 1.71-9.81, p<0.0001) were independent factors associated to CR achievement. Younger age, good performance status, favorable genetic risk and no development of PP-IFD (HR 1.86, 95% CI 1.20-2.88, p=0.005) were independent factors associated to OS at 3 years.

  4. Long-term tolerability of capnography and respiratory inductance plethysmography for respiratory monitoring in pediatric patients treated with patient-controlled analgesia

    PubMed Central

    Miller, Karen M.; Kim, Andrew Y.; Yaster, Myron; Kudchadkar, Sapna R.; White, Elizabeth; Fackler, James; Monitto, Constance L.

    2016-01-01

    Background The Anesthesia Patient Safety Foundation has advocated the use of continuous electronic monitoring of oxygenation and ventilation to preemptively identify opioid-induced respiratory depression. In adults, capnography is the gold standard in respiratory monitoring. An alternative technique used in sleep laboratories is respiratory inductance plethysmography (RIP). However, it is not known if either monitor is well tolerated by pediatric patients for prolonged periods of time. Aim The goal of this study was to determine whether capnography or RIP is better tolerated in non-intubated, spontaneously breathing pediatric patients being treated with intravenous patient-controlled analgesia (IVPCA). Methods Nasal cannula capnography with oral sampling and thoracic and abdominal inductance plethysmography bands were placed along with routine monitors on pediatric patients being treated for acute pain with IVPCA. Study monitors were left in place for as long as they were tolerated by the patient, for a maximum of 24 consecutive hours. If the patient did not wear a particular study monitor for any reason, but tolerated the remaining monitor, participation in the study continued. If the patient would not wear either monitor, participation was terminated. Results Twenty-six patients (18 female, 8 male, average age 10.1 ± 5.5 years) consented to participate, but only 14 patients attempted to wear one or both devices. Among those who wore either device, median time to device removal was 8.33 hours (range 0.3–23.6 hours) for capnography and 23.5 hours (range 0.7–24 hours) for RIP bands. Conclusion Children did not tolerate wearing capnography cannulae for prolonged periods of time, limiting the usefulness of this device as a continuous monitor of ventilation in children. RIP bands were better tolerated; however, they require further assessment of their utility. Until more effective, child-friendly monitors are developed and their utility validated, guidelines

  5. A Power-Efficient Bio-Potential Acquisition Device with DS-MDE Sensors for Long-Term Healthcare Monitoring Applications

    PubMed Central

    Chang, Chia-Lin; Chang, Chih-Wei; Huang, Hong-Yi; Hsu, Chen-Ming; Huang, Chia-Hsuan; Chiou, Jin-Chern; Luo, Ching-Hsing

    2010-01-01

    This work describes a power-efficient bio-potential acquisition device for long-term healthcare applications that is implemented using novel microelectromechanical dry electrodes (MDE) and a low power bio-potential processing chip. Using micromachining technology, an attempt is also made to enhance the sensing reliability and stability by fabricating a diamond-shaped MDE (DS-MDE) that has a satisfactory self-stability capability and superior electric conductivity when attached onto skin without any extra skin tissue injury technology. To acquire differential bio-potentials such as ECG signals, the proposed processing chip fabricated in a standard CMOS process has a high common mode rejection ratio (C.M.R.R.) differential amplifier and a 12-bit analog-to-digital converter (ADC). Use of the proposed system and integrate simple peripheral commercial devices can obtain the ECG signal efficiently without additional skin tissue injury and ensure continuous monitoring more than 70 hours with a 400 mAh battery. PMID:22399907

  6. Caffeine treatment prevents rapid eye movement sleep deprivation-induced impairment of late-phase long-term potentiation in the dentate gyrus.

    PubMed

    Alhaider, Ibrahim A; Alkadhi, Karim A

    2015-11-01

    The CA1 and dentate gyrus (DG) are physically and functionally closely related areas of the hippocampus, but they differ in various respects, including their reactions to different insults. The purpose of this study was to determine the protective effects of chronic caffeine treatment on late-phase long-term potentiation (L-LTP) and its signalling cascade in the DG area of the hippocampus of rapid eye movement sleep-deprived rats. Rats were chronically treated with caffeine (300 mg/L drinking water) for 4 weeks, after which they were sleep-deprived for 24 h. L-LTP was induced in in anaesthetized rats, and extracellular field potentials from the DG area were recorded in vivo. The levels of L-LTP-related signalling proteins were assessed by western blot analysis. Sleep deprivation markedly reduced L-LTP magnitude, and basal levels of total cAMP response element-binding protein (CREB), phosphorylated CREB (P-CREB), and calcium/calmodulin kinase IV (CaMKIV). Chronic caffeine treatment prevented the reductions in the basal levels of P-CREB, total CREB and CaMKIV in sleep-deprived rats. Furthermore, caffeine prevented post-L-LTP sleep deprivation-induced downregulation of P-CREB and brain-derived neurotrophic factor in the DG. The current findings show that caffeine treatment prevents acute sleep deprivation-induced deficits in brain function.

  7. Modulation of DL-. alpha. -amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid/quisqualate receptors by phospholipase A sub 2 : A necessary step in long-term potentiation

    SciTech Connect

    Massicotte, G.; Baudry, M. ); Vanderklish, P.; Lynch, G. )

    1991-03-01

    The effects of kainate (KA)-induced epileptic seizures on the binding properites of hippocampal glutamate receptors, on the modulation of DL-{alpha}-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA)/quisqualate receptor by phospholipase A{sub 2} (PLA{sub 2}), and on the formation of long-term potentiation (LTP) were studied in hippocampal membranes and hippocampal slices. Systemic administration of KA produced specific changes in the binding properties of the AMPA/quisqualate receptors and its regulation. Whereas the binding of various ligands to the N-methyl-D-aspartate receptors was not modified by KA treatment, there was a singificant decrease in the maximal number of binding sites for ({sup 3}H)AMPA. The loss of LTP was not due to changes in postsynaptic responses elicited by the bursts that trigger the potentiation effect, thus suggesting that KA treatment disrupts processes that follow N-methyl-D-aspartate receptor activation. Systemic administration of KA was associated with calpain activation as the amount of spectrin breakdown products was increased severalfold in hippocampus but not in cerebellum. Pretreatment of telencephalic membranes with calpain greatly reduced the PLA{sub 2}-induced increase in ({sup 3}H)AMPA binding. The results provide evidence in favor of an essential role of PLA{sub 2} in the development of LTP and suggest that the order of activation of different calcium-dependent processes is critical for producing the final changes underlying LTP.

  8. The protective effect of Borago Officinalis extract on amyloid β (25-35)-induced long term potentiation disruption in the dentate gyrus of male rats.

    PubMed

    Zargooshnia, Somayeh; Shahidi, Siamak; Ghahremanitamadon, Fatemeh; Nikkhah, Ali; Mehdizadeh, Mehdi; Soleimani Asl, Sara

    2015-02-01

    Alzheimer's disease (AD) begins with impairment in synaptic functions before developing into later neurodegeneration and neural loss. In the present study we have examined the protective effects of Borago Officinalis (borage) extract on amyloid β (Aβ)--Induced long term potentiation (LTP) disruption in hippocampal dentate gyrus (DG). Wistar male rats received intrahippocampal (IHP) injection of the Aβ (25-35) and borage extract throughout gestation (100 mg/kg). LTP in perforant path- DG synapses was assessed using electrophysiology method and field excitatory post- synaptic potential (fEPSP) slope and population spike (PS) amplitude were measured by 400 Hz tetanization. Finally, the total thiol content of hippocampus was measured using colorimetric reaction based on the Ellman's method. The results showed that Aβ (25-35) significantly decreased fEPSP slope and SP amplitude comparing with the control and sham group, whereas borage extract administration increased these parameters compared to the Aβ group. Aβ induced a remarkable decrease in total thiol content of hippocampus and borage prevented the decrease of the hippocampal total sulfhydryl (SH) groups. This data suggest that Aβ (25-35) can effectively inhibit LTP in the granular cells of the DG in hippocampus, and borage supplementation reverse the synaptic plasticity in DG following Aβ treatment and that borage consumption may lead to an improvement of AD-induced cognitive dysfunction. PMID:25060965

  9. A brief, but repeated, swimming protocol is sufficient to overcome amyloid beta-protein inhibition of hippocampal long-term potentiation.

    PubMed

    Li, Shaomin; Feig, Larry A; Hartley, Dean M

    2007-09-01

    Alzheimer's disease starts as an almost imperceptible malady, first observed clinically as a mild memory problem. Accumulating genetic and biochemical data have suggested that amyloid beta-protein (Abeta) plays an important role in this memory loss, and Abeta has been shown to suppress long-term potentiation (LTP), a cellular model for memory and learning. Here we show that a very brief (3 min) swimming, twice daily for 2 weeks, rescues LTP inhibition in the CA1 region of hippocampal slices caused by Abeta(42) or Abeta(40) carrying the Arctic mutation using a theta burst stimulation (TBS) protocol. Whereas the input-output curve was not affected, the paired-pulse ratio was reduced in mice receiving our repeated swimming protocol, suggesting a possible involvement of presynaptic facilitation. Similar to swimming, Abeta's inhibition of LTP could be rescued with the adenylyl cyclase, forskolin. Interestingly, this swimming protocol produced conditions in which a weak-TBS could invoke LTP not observed in naïve mice, which again was mimicked by forskolin. In contrast, the protein kinase A (PKA) inhibitor, H89, blocked both the forskolin and swimming potentiation of LTP; these data implicate cAMP/PKA signaling in the protective effect of swimming and mediating Abeta' detrimental effects. Our data add a new simple behavior paradigm that shows the importance of an environmental factor in reversing the pathophysiological effects of Abeta, and suggest new therapeutic avenues.

  10. Caffeine treatment prevents rapid eye movement sleep deprivation-induced impairment of late-phase long-term potentiation in the dentate gyrus.

    PubMed

    Alhaider, Ibrahim A; Alkadhi, Karim A

    2015-11-01

    The CA1 and dentate gyrus (DG) are physically and functionally closely related areas of the hippocampus, but they differ in various respects, including their reactions to different insults. The purpose of this study was to determine the protective effects of chronic caffeine treatment on late-phase long-term potentiation (L-LTP) and its signalling cascade in the DG area of the hippocampus of rapid eye movement sleep-deprived rats. Rats were chronically treated with caffeine (300 mg/L drinking water) for 4 weeks, after which they were sleep-deprived for 24 h. L-LTP was induced in in anaesthetized rats, and extracellular field potentials from the DG area were recorded in vivo. The levels of L-LTP-related signalling proteins were assessed by western blot analysis. Sleep deprivation markedly reduced L-LTP magnitude, and basal levels of total cAMP response element-binding protein (CREB), phosphorylated CREB (P-CREB), and calcium/calmodulin kinase IV (CaMKIV). Chronic caffeine treatment prevented the reductions in the basal levels of P-CREB, total CREB and CaMKIV in sleep-deprived rats. Furthermore, caffeine prevented post-L-LTP sleep deprivation-induced downregulation of P-CREB and brain-derived neurotrophic factor in the DG. The current findings show that caffeine treatment prevents acute sleep deprivation-induced deficits in brain function. PMID:26449851

  11. The protective effect of Borago Officinalis extract on amyloid β (25-35)-induced long term potentiation disruption in the dentate gyrus of male rats.

    PubMed

    Zargooshnia, Somayeh; Shahidi, Siamak; Ghahremanitamadon, Fatemeh; Nikkhah, Ali; Mehdizadeh, Mehdi; Soleimani Asl, Sara

    2015-02-01

    Alzheimer's disease (AD) begins with impairment in synaptic functions before developing into later neurodegeneration and neural loss. In the present study we have examined the protective effects of Borago Officinalis (borage) extract on amyloid β (Aβ)--Induced long term potentiation (LTP) disruption in hippocampal dentate gyrus (DG). Wistar male rats received intrahippocampal (IHP) injection of the Aβ (25-35) and borage extract throughout gestation (100 mg/kg). LTP in perforant path- DG synapses was assessed using electrophysiology method and field excitatory post- synaptic potential (fEPSP) slope and population spike (PS) amplitude were measured by 400 Hz tetanization. Finally, the total thiol content of hippocampus was measured using colorimetric reaction based on the Ellman's method. The results showed that Aβ (25-35) significantly decreased fEPSP slope and SP amplitude comparing with the control and sham group, whereas borage extract administration increased these parameters compared to the Aβ group. Aβ induced a remarkable decrease in total thiol content of hippocampus and borage prevented the decrease of the hippocampal total sulfhydryl (SH) groups. This data suggest that Aβ (25-35) can effectively inhibit LTP in the granular cells of the DG in hippocampus, and borage supplementation reverse the synaptic plasticity in DG following Aβ treatment and that borage consumption may lead to an improvement of AD-induced cognitive dysfunction.

  12. An exploration of the effectiveness of artificial mini-magnetospheres as a potential Solar Storm shelter for long term human space missions

    NASA Astrophysics Data System (ADS)

    Bamford, Ruth; Kellett, Barry; Bradford, John; Todd, Tom N.; Stafford-Allen, Robin; Alves, E. Paulo; Silva, Luis; Collingwood, Cheryl; Crawford, Ian A.; Bingham, Robert

    2014-12-01

    In this paper we explore the effectiveness of an artificial mini-magnetosphere as a potential radiation shelter for long term human space missions. Our study includes the differences that the plasma environment makes to the efficiency of the shielding from the high energy charged particle component of solar and cosmic rays, which radically alters the power requirements. The incoming electrostatic charges are shielded by fields supported by the self captured environmental plasma of the solar wind, potentially augmented with additional density. The artificial magnetic field generated on board acts as the means of confinement and control. Evidence for similar behaviour of electromagnetic fields and ionised particles in interplanetary space can be gained by the example of the enhanced shielding effectiveness of naturally occurring "mini-magnetospheres" on the moon. The shielding effect of surface magnetic fields of the order of ~100s nanoTesla is sufficient to provide effective shielding from solar proton bombardment that culminate in visible discolouration of the lunar regolith known as "lunar swirls". Supporting evidence comes from theory, laboratory experiments and computer simulations that have been obtained on this topic. The result of this work is, hopefully, to provide the tools for a more realistic estimation of the resources versus effectiveness and risk that spacecraft engineers need to work with in designing radiation protection for long-duration human space missions.

  13. Quantifying the benefit of wellbore leakage potential estimates for prioritizing long-term MVA well sampling at a CO2 storage site.

    PubMed

    Azzolina, Nicholas A; Small, Mitchell J; Nakles, David V; Glazewski, Kyle A; Peck, Wesley D; Gorecki, Charles D; Bromhal, Grant S; Dilmore, Robert M

    2015-01-20

    This work uses probabilistic methods to simulate a hypothetical geologic CO2 storage site in a depleted oil and gas field, where the large number of legacy wells would make it cost-prohibitive to sample all wells for all measurements as part of the postinjection site care. Deep well leakage potential scores were assigned to the wells using a random subsample of 100 wells from a detailed study of 826 legacy wells that penetrate the basal Cambrian formation on the U.S. side of the U.S./Canadian border. Analytical solutions and Monte Carlo simulations were used to quantify the statistical power of selecting a leaking well. Power curves were developed as a function of (1) the number of leaking wells within the Area of Review; (2) the sampling design (random or judgmental, choosing first the wells with the highest deep leakage potential scores); (3) the number of wells included in the monitoring sampling plan; and (4) the relationship between a well’s leakage potential score and its relative probability of leakage. Cases where the deep well leakage potential scores are fully or partially informative of the relative leakage probability are compared to a noninformative base case in which leakage is equiprobable across all wells in the Area of Review. The results show that accurate prior knowledge about the probability of well leakage adds measurable value to the ability to detect a leaking well during the monitoring program, and that the loss in detection ability due to imperfect knowledge of the leakage probability can be quantified. This work underscores the importance of a data-driven, risk-based monitoring program that incorporates uncertainty quantification into long-term monitoring sampling plans at geologic CO2 storage sites.

  14. Effects of neonatal exposure to the flame retardant tetrabromobisphenol-A, aluminum diethylphosphinate or zinc stannate on long-term potentiation and synaptic protein levels in mice.

    PubMed

    Hendriks, Hester S; Koolen, Lucas A E; Dingemans, Milou M L; Viberg, Henrik; Lee, Iwa; Leonards, Pim E G; Ramakers, Geert M J; Westerink, Remco H S

    2015-12-01

    Brominated flame retardants such as tetrabromobisphenol-A (TBBPA) may exert (developmental) neurotoxic effects. However, data on (neuro)toxicity of halogen-free flame retardants (HFFRs) are scarce. Recent in vitro studies indicated a high neurotoxic potential for some HFFRs, e.g., zinc stannate (ZS), whereas the neurotoxic potential of other HFFRs, such as aluminum diethylphosphinate (Alpi), appears low. However, the in vivo (neuro)toxicity of these compounds is largely unknown. We therefore investigated effects of neonatal exposure to TBBPA, Alpi or ZS on synaptic plasticity in mouse hippocampus. Male C57bl/6 mice received a single oral dose of 211 µmol/kg bw TBBPA, Alpi or ZS on postnatal day (PND) 10. On PND 17-19, effects on hippocampal synaptic plasticity were investigated using ex vivo extracellular field recordings. Additionally, we measured levels of postsynaptic proteins involved in long-term potentiation (LTP) as well as flame retardant concentrations in brain, muscle and liver tissues. All three flame retardants induced minor, but insignificant, effects on LTP. Additionally, TBBPA induced a minor decrease in post-tetanic potentiation. Despite these minor effects, expression of selected synaptic proteins involved in LTP was not affected. The flame retardants could not be measured in significant amounts in the brains, suggesting low bioavailability and/or rapid elimination/metabolism. We therefore conclude that a single neonatal exposure on PND 10 to TBBPA, Alpi or ZS does affect neurodevelopment and synaptic plasticity only to a small extent in mice. Additional data, in particular on persistence, bioaccumulation and (in vivo) toxicity, following prolonged (developmental) exposure are required for further (human) risk assessment.

  15. Quantifying the benefit of wellbore leakage potential estimates for prioritizing long-term MVA well sampling at a CO2 storage site.

    PubMed

    Azzolina, Nicholas A; Small, Mitchell J; Nakles, David V; Glazewski, Kyle A; Peck, Wesley D; Gorecki, Charles D; Bromhal, Grant S; Dilmore, Robert M

    2015-01-20

    This work uses probabilistic methods to simulate a hypothetical geologic CO2 storage site in a depleted oil and gas field, where the large number of legacy wells would make it cost-prohibitive to sample all wells for all measurements as part of the postinjection site care. Deep well leakage potential scores were assigned to the wells using a random subsample of 100 wells from a detailed study of 826 legacy wells that penetrate the basal Cambrian formation on the U.S. side of the U.S./Canadian border. Analytical solutions and Monte Carlo simulations were used to quantify the statistical power of selecting a leaking well. Power curves were developed as a function of (1) the number of leaking wells within the Area of Review; (2) the sampling design (random or judgmental, choosing first the wells with the highest deep leakage potential scores); (3) the number of wells included in the monitoring sampling plan; and (4) the relationship between a well’s leakage potential score and its relative probability of leakage. Cases where the deep well leakage potential scores are fully or partially informative of the relative leakage probability are compared to a noninformative base case in which leakage is equiprobable across all wells in the Area of Review. The results show that accurate prior knowledge about the probability of well leakage adds measurable value to the ability to detect a leaking well during the monitoring program, and that the loss in detection ability due to imperfect knowledge of the leakage probability can be quantified. This work underscores the importance of a data-driven, risk-based monitoring program that incorporates uncertainty quantification into long-term monitoring sampling plans at geologic CO2 storage sites. PMID:25551254

  16. Rescue of Cyclic AMP Mediated Long Term Potentiation Impairment in the Hippocampus of Mecp2 Knockout (Mecp2-/y) Mice by Rolipram

    PubMed Central

    Balakrishnan, Saju; Niebert, Marcus; Richter, Diethelm W.

    2016-01-01

    Rett syndrome (RTT) patients experience learning difficulties and memory loss. Analogous deficits of hippocampal plasticity are reported in mouse models of RTT. To elucidate the underlying pathophysiology, we studied long term potentiation (LTP) at the CA3 to CA1 synapses in the hippocampus in acute brain slices from WT and Mecp2-/y mice, by either activating cAMP dependent pathway or using high frequency stimulation, by means of patch clamp. We have observed that, the NMDA channel current characteristics remain unchanged in the Mecp2-/y mice. The adenylyl cyclase (AC) agonist forskolin evoked a long lasting potentiation of evoked EPSCs in WT CA1 neurons, but only minimally enhanced the EPSCs in the Mecp2-/y mice. This weaker potentiation in Mecp2-/y mice was ameliorated by application of phosphodiesterase 4 inhibitor rolipram. The hyperpolarization activated cyclic nucleotide gated channel current (Ih) was potentiated to similar extent by forskolin in both phenotypes. Multiple tetanus induced cAMP-dependent plasticity was also impaired in the Mecp2-/y mice, and was also partially rescued by rolipram. Western blot analysis of CA region of Mecp2-/y mice hippocampus revealed more than twofold up-regulation of protein kinase A (PKA) regulatory subunits, while the expression of the catalytic subunit remained unchanged. We hypothesize that the overexpressed PKA regulatory subunits buffer cAMP and restrict the PKA mediated phosphorylation of target proteins necessary for LTP. Blocking the degradation of cAMP, thereby saturating the regulatory subunits alleviated this defect. PMID:26869885

  17. Modulation of Long-Term Potentiation of Cortico-Amygdala Synaptic Responses and Auditory Fear Memory by Dietary Polyunsaturated Fatty Acid

    PubMed Central

    Yamada, Daisuke; Wada, Keiji; Sekiguchi, Masayuki

    2016-01-01

    Converging evidence suggests that an imbalance of ω3 to ω6 polyunsaturated fatty acid (PUFA) in the brain is involved in mental illnesses such as anxiety disorders. However, the underlying mechanism is unknown. We previously reported that the dietary ratio of ω3 to ω6 PUFA alters this ratio in the brain, and influences contextual fear memory. In addition to behavioral change, enhancement of cannabinoid CB1 receptor-mediated short-term synaptic plasticity and facilitation of the agonist sensitivity of CB1 receptors have been observed in excitatory synaptic responses in the basolateral nucleus of the amygdala (BLA). However, it is not known whether long-term synaptic plasticity in the amygdala is influenced by the dietary ratio of ω3 to ω6 PUFA. In the present study, we examined long-term potentiation (LTP) of optogenetically-evoked excitatory synaptic responses in synapses between the terminal of the projection from the auditory cortex (ACx) and the pyramidal cells in the lateral nucleus of the amygdala. We found that LTP in this pathway was attenuated in mice fed with a high ω3 to ω6 PUFA ratio diet (0.97), compared with mice fed with a low ω3 to ω6 PUFA ratio diet (0.14). Furthermore, mice in the former condition showed reduced fear responses in an auditory fear conditioning test, compared with mice in the latter condition. In both electrophysiological and behavioral experiments, the effect of a diet with a high ω3 to ω6 PUFA diet ratio was completely blocked by treatment with a CB1 receptor antagonist. Furthermore, a significant reduction was observed in cholesterol content, but not in the level of an endogenous CB1 receptor agonist, 2-arachidonoylglycerol (2-AG), in brain samples containing the amygdala. These results suggest that the balance of ω3 to ω6 PUFA has an impact on fear memory and cortico-amygdala synaptic plasticity, both in a CB1 receptor–dependent manner.

  18. Modulation of Long-Term Potentiation of Cortico-Amygdala Synaptic Responses and Auditory Fear Memory by Dietary Polyunsaturated Fatty Acid

    PubMed Central

    Yamada, Daisuke; Wada, Keiji; Sekiguchi, Masayuki

    2016-01-01

    Converging evidence suggests that an imbalance of ω3 to ω6 polyunsaturated fatty acid (PUFA) in the brain is involved in mental illnesses such as anxiety disorders. However, the underlying mechanism is unknown. We previously reported that the dietary ratio of ω3 to ω6 PUFA alters this ratio in the brain, and influences contextual fear memory. In addition to behavioral change, enhancement of cannabinoid CB1 receptor-mediated short-term synaptic plasticity and facilitation of the agonist sensitivity of CB1 receptors have been observed in excitatory synaptic responses in the basolateral nucleus of the amygdala (BLA). However, it is not known whether long-term synaptic plasticity in the amygdala is influenced by the dietary ratio of ω3 to ω6 PUFA. In the present study, we examined long-term potentiation (LTP) of optogenetically-evoked excitatory synaptic responses in synapses between the terminal of the projection from the auditory cortex (ACx) and the pyramidal cells in the lateral nucleus of the amygdala. We found that LTP in this pathway was attenuated in mice fed with a high ω3 to ω6 PUFA ratio diet (0.97), compared with mice fed with a low ω3 to ω6 PUFA ratio diet (0.14). Furthermore, mice in the former condition showed reduced fear responses in an auditory fear conditioning test, compared with mice in the latter condition. In both electrophysiological and behavioral experiments, the effect of a diet with a high ω3 to ω6 PUFA diet ratio was completely blocked by treatment with a CB1 receptor antagonist. Furthermore, a significant reduction was observed in cholesterol content, but not in the level of an endogenous CB1 receptor agonist, 2-arachidonoylglycerol (2-AG), in brain samples containing the amygdala. These results suggest that the balance of ω3 to ω6 PUFA has an impact on fear memory and cortico-amygdala synaptic plasticity, both in a CB1 receptor–dependent manner. PMID:27601985

  19. Modulation of Long-Term Potentiation of Cortico-Amygdala Synaptic Responses and Auditory Fear Memory by Dietary Polyunsaturated Fatty Acid.

    PubMed

    Yamada, Daisuke; Wada, Keiji; Sekiguchi, Masayuki

    2016-01-01

    Converging evidence suggests that an imbalance of ω3 to ω6 polyunsaturated fatty acid (PUFA) in the brain is involved in mental illnesses such as anxiety disorders. However, the underlying mechanism is unknown. We previously reported that the dietary ratio of ω3 to ω6 PUFA alters this ratio in the brain, and influences contextual fear memory. In addition to behavioral change, enhancement of cannabinoid CB1 receptor-mediated short-term synaptic plasticity and facilitation of the agonist sensitivity of CB1 receptors have been observed in excitatory synaptic responses in the basolateral nucleus of the amygdala (BLA). However, it is not known whether long-term synaptic plasticity in the amygdala is influenced by the dietary ratio of ω3 to ω6 PUFA. In the present study, we examined long-term potentiation (LTP) of optogenetically-evoked excitatory synaptic responses in synapses between the terminal of the projection from the auditory cortex (ACx) and the pyramidal cells in the lateral nucleus of the amygdala. We found that LTP in this pathway was attenuated in mice fed with a high ω3 to ω6 PUFA ratio diet (0.97), compared with mice fed with a low ω3 to ω6 PUFA ratio diet (0.14). Furthermore, mice in the former condition showed reduced fear responses in an auditory fear conditioning test, compared with mice in the latter condition. In both electrophysiological and behavioral experiments, the effect of a diet with a high ω3 to ω6 PUFA diet ratio was completely blocked by treatment with a CB1 receptor antagonist. Furthermore, a significant reduction was observed in cholesterol content, but not in the level of an endogenous CB1 receptor agonist, 2-arachidonoylglycerol (2-AG), in brain samples containing the amygdala. These results suggest that the balance of ω3 to ω6 PUFA has an impact on fear memory and cortico-amygdala synaptic plasticity, both in a CB1 receptor-dependent manner. PMID:27601985

  20. Arsenic downregulates gene expression at the postsynaptic density in mouse cerebellum, including genes responsible for long-term potentiation and depression.

    PubMed

    Zhang, Cong; Li, Sheng; Sun, Yahui; Dong, Wei; Piao, Fengyuan; Piao, Yongjun; Liu, Shuang; Guan, Huai; Yu, Shengbo

    2014-08-01

    Arsenic (As) is a neurotoxin induces dysfunction of learning and memory. Research has indicated that cerebellum may be involved in arsenic-induced impairment of learning and memory. However, the molecular mechanisms that underlie these effects remain unclear. This study screened for the differentially expressed genes related to the long-term potentiation and long-term depression (LTP and LTD) at the cerebellar postsynaptic density (PSD) of mice following exposure to arsenic, and we provide evidence of the mechanism by which arsenic adversely affects the functions of learning and memory. Here, SPF mice were exposed to 1ppm, 2ppm and 4ppm As2O3 for 60 days. The ultrastructure of the synapses in cerebella of these mice was observed via transmission electron microscopy. The cerebellum global gene expression of mice exposed to 4ppm As2O3 was determined through GeneChip analysis. We used the web tool DAVID to analyze the Gene Ontology (GO) and KEGG pathways that were significantly enriched among the differentially expressed genes. Our observations of synaptic ultrastructure showed that the thickness of the cerebellar PSD was reduced in mice exposed to arsenic. Go analysis revealed the PSD as a significantly altered cellular component. KEGG pathway analysis showed that LTP and LTD were affected by arsenic with highest statistical significance, and 20 differentially expressed genes were associated with them. Among these differentially expressed genes, significant decreases in the mRNA expressions of CaMKII, Gria1, Gria2, Grin1, Itpr1, Grm1 and PLCβ4 related to the LTP and LTD were found at the PSD of mouse cerebellum exposed to arsenic. The downregulation of these genes was further confirmed via real-time reverse transcription PCR or Western blot at 1ppm, 2ppm and 4ppm As2O3. Our results indicate that the 7 genes with in cerebellar PSDs may be involved in arsenic-induced neurotoxicity, including impairment of learning and memory. PMID:24831965

  1. Methodological Aspects of the Potential Use of Dendrochronological Techniques When Analyzing the Long-Term Impact of Tourism on Protected Areas.

    PubMed

    Ciapała, Szymon; Adamski, Paweł

    2015-01-01

    Intensification of pedestrian tourism causes damage to trees near tourist tracks, and likewise changes the soil structure. As a result, one may expect that annual amount of trees growing near tracks is significantly lower than deeper in the forest. However, during the study of the long-term impact of tourism on the environment (determined from tree increment dynamics), some methodological problems may occur. It is particularly important in protected areas where law and administrative regulations related to nature conservation force research to be conducted using small samples. In this paper we have analyzed the data collected in the Polish part of the Tatra National Park in the two study plots divided into two zones each: the area directly under the influence of the tourist's trampling and the control group. The aim of such analyses was to present the potential effects of the factors which may affect the results of dendrochronological analysis: (i) small size of samples that affects their representativeness, (ii) spatial differences in the rates of the process, as a result of spatial variability of environmental factors and (iii) temporal differences in the rates of the process. This study confirms that the factors mentioned above could significantly influence the results and should be taken into consideration during the analysis. PMID:26325062

  2. The group I metabotropic glutamate receptor mGluR5 is required for fear memory formation and long-term potentiation in the lateral amygdala.

    PubMed

    Rodrigues, Sarina M; Bauer, Elizabeth P; Farb, Claudia R; Schafe, Glenn E; LeDoux, Joseph E

    2002-06-15

    The group I metabotropic glutamate receptor subtype mGluR5 has been shown to play a key role in the modulation of synaptic plasticity. The present experiments examined the function of mGluR5 in the circuitry underlying Pavlovian fear conditioning using neuroanatomical, electrophysiological, and behavioral techniques. First, we show using immunocytochemical and tract-tracing methods that mGluR5 is localized to dendritic shafts and spines in the lateral nucleus of the amygdala (LA) and is postsynaptic to auditory thalamic inputs. In electrophysiological experiments, we show that long-term potentiation at thalamic input synapses to the LA is impaired by bath application of a specific mGluR5 antagonist, 2-methyl-6-(phenyle-thynyl)-pyridine (MPEP), in vitro. Finally, we show that intra-amygdala administration of MPEP dose-dependently impairs the acquisition, but not expression or consolidation, of auditory and contextual fear conditioning. Collectively, the results of this study indicate that mGluR5 in the LA plays a crucial role in fear conditioning and in plasticity at synapses involved in fear conditioning.

  3. Methodological Aspects of the Potential Use of Dendrochronological Techniques When Analyzing the Long-Term Impact of Tourism on Protected Areas

    PubMed Central

    Ciapała, Szymon; Adamski, Paweł

    2015-01-01

    Intensification of pedestrian tourism causes damage to trees near tourist tracks, and likewise changes the soil structure. As a result, one may expect that annual amount of trees growing near tracks is significantly lower than deeper in the forest. However, during the study of the long-term impact of tourism on the environment (determined from tree increment dynamics), some methodological problems may occur. It is particularly important in protected areas where law and administrative regulations related to nature conservation force research to be conducted using small samples. In this paper we have analyzed the data collected in the Polish part of the Tatra National Park in the two study plots divided into two zones each: the area directly under the influence of the tourist's trampling and the control group. The aim of such analyses was to present the potential effects of the factors which may affect the results of dendrochronological analysis: (i) small size of samples that affects their representativeness, (ii) spatial differences in the rates of the process, as a result of spatial variability of environmental factors and (iii) temporal differences in the rates of the process. This study confirms that the factors mentioned above could significantly influence the results and should be taken into consideration during the analysis. PMID:26325062

  4. TRPA1 Channels Are Regulators of Astrocyte Basal Calcium Levels and Long-Term Potentiation via Constitutive d-Serine Release

    PubMed Central

    Shigetomi, Eiji; Jackson-Weaver, Olan; Huckstepp, Robert T.

    2013-01-01

    Astrocytes are found throughout the brain where they make extensive contacts with neurons and synapses. Astrocytes are known to display intracellular Ca2+ signals and release signaling molecules such as d-serine into the extracellular space. However, the role(s) of astrocyte Ca2+ signals in hippocampal long-term potentiation (LTP), a form of synaptic plasticity involved in learning and memory, remains unclear. Here, we explored a recently discovered novel TRPA1 channel-mediated transmembrane Ca2+ flux pathway in astrocytes. Specifically, we determined whether block or genetic deletion of TRPA1 channels affected LTP of Schaffer collateral to CA1 pyramidal neuron synapses. Using pharmacology, TRPA1−/− mice, imaging, electrophysiology, and d-serine biosensors, our data indicate that astrocyte TRPA1 channels contribute to basal Ca2+ levels and are required for constitutive d-serine release into the extracellular space, which contributes to NMDA receptor-dependent LTP. The findings have broad relevance for the study of astrocyte–neuron interactions by demonstrating how TRPA1 channel-mediated fluxes contribute to astrocyte basal Ca2+ levels and neuronal function via constitutive d-serine release. PMID:23761909

  5. Long-term effects of application of sewage sludge to soil on composition of herbage with respect to potentially toxic elements.

    PubMed

    Purves, D

    1986-03-01

    Repeated applications of metal-contaminated sewage sludge can have a drastic effect on soil levels of trace elements and lead to serious toxicity effects in plants. In some cases, land can be rendered sterile.It has been demonstrated that contamination of soils with respect to cadmium, copper, lead, mercury, nickel and zinc is largely irreversible, although there does appear to be a long-term tendency for these metals to become progressively less available to plants over a long period of time. Most national guidelines designed to regulate the disposal of sewage sludge on agricultural land are based on the assumption that relatively rapid fixation of contaminant metals does take place in the soil after sludge application. There is a dearth of information relating to the rates at which potentially toxic-elements commonly present in sewage sludge become immobilised in soils, although it is clear that contaminant boron can be leached down the profile in the short term.Evidence is presented that contamination of top soil can persist for a period of six years after a single application of sludge (150 tonnes dry matter/ha). Over this period, there was little change in 'available' levels of boron, cadmium, copper, lead and zinc in the top soil and the degree of enhancement of these elements in perennial ryegrass grown in the sludge-treated area remained more or less unchanged. PMID:24213837

  6. Enhancement of hippocampal long-term potentiation induced by cocaine self-administration is maintained during the extinction of this behavior.

    PubMed

    del Olmo, Nuria; Miguéns, Miguel; Higuera-Matas, Alejandro; Torres, Isabel; García-Lecumberri, Carmen; Solís, José María; Ambrosio, Emilio

    2006-10-20

    Drug addiction may involve learning and memory processes requiring the participation of hippocampal formation. One of the best studied examples of hippocampal synaptic plasticity is the long-term potentiation (LTP) which usually occurs when hippocampal synapses are stimulated with high-frequency stimulation. The aim of this work has been to study the effect of extinction of cocaine self-administration behavior on synaptic plasticity in rat hippocampal slices. LTP was induced using a tetanization paradigm consisting of a single train of high-frequency (100 Hz) stimulation for one second. This tetanization protocol evoked a greater and more perdurable LTP in slices obtained after 10 days of extinction of cocaine self-administration (1 mg/kg/injection) than that elicited in slices from saline self-administering (0.9% NaCl) animals. In addition, this LTP facilitation in animals which have followed the cocaine self-administration extinction protocol was very similar to that obtained in slices from cocaine self-administering animals. These results suggest that chronic cocaine self-administration induces enduring neuroadaptive changes in hippocampal synaptic plasticity which last even after the extinction of this behavior and that they may be involved in cocaine dependence.

  7. Levothyroxine rescues the lead-induced hypothyroidism and impairment of long-term potentiation in hippocampal CA1 region of the developmental rats

    SciTech Connect

    Wu Chuanyun; Liu Bing; Wang Huili; Ruan Diyun

    2011-10-15

    Lead (Pb) exposure during development has been associated with impaired long-term potentiation (LTP). Hypothyroidism happening upon subjects with occupational exposure to Pb is suggestive of an adverse effect of Pb on thyroid homeostasis, leading to the hypothesis that Pb exposure may alter thyroid hormone homeostasis. Hippocampus is one of the targets of Pb exposure, and is sensitive to and dependent on thyroid hormones, leading us to explore whether levothyroxine (L-T{sub 4}) administration could alter the thyroid disequilibrium and impairment of LTP in rat hippocampus caused by Pb exposure. Our results show that Pb exposure caused a decrease in triiodothyronine (T{sub 3}) and tetraiodothyronine (T{sub 4}) levels accompanied by a dramatic decrease of TSH and application of L-T{sub 4} restored these changes to about control levels. Hippocampal and blood Pb concentration were significantly reduced following L-T{sub 4} treatment. L-T{sub 4} treatment rescued the impairment of LTP induced by the Pb exposure. These results suggest that Pb exposure may lead to thyroid dysfunction and induce hypothyroidism and provide a direct electrophysiological proof that L-T{sub 4} relieves chronic Pb exposure-induced impairment of synaptic plasticity. - Highlights: > Lead may interfere with thyroid hormone homeostasis and induce hypothyroidism. > Levothyroxine decreases the hippocampal and blood Pb concentration. > Levothyroxine amends the T{sub 3}, T{sub 4} and TSH levels in blood. > Levothyroxine rescues the impaired LTP in CA1.

  8. Exendin-4 antagonizes Aβ1-42-induced suppression of long-term potentiation by regulating intracellular calcium homeostasis in rat hippocampal neurons.

    PubMed

    Wang, Xiaohui; Wang, Li; Jiang, Ruirui; Yuan, Yuan; Yu, Qianqian; Li, Yameng

    2015-11-19

    An imbalance of intracellular calcium homeostasis induced by amyloid β-protein (Aβ) contributes to the pathogenesis of Alzheimer's disease (AD), such as deficits in learning and memory. Therefore, regulation of calcium homeostasis may represent a new strategy for treatment of AD. Growing evidence suggests that type 2 diabetes mellitus (T2DM) and AD are closely related in pathogenesis. Thus, drugs used in treatment of T2DM may modify the pathogenesis of AD. This study demonstrated that Exendin-4, which is a glucagon-like peptide-1 (GLP-1) analog used as a therapeutic drug for T2DM, significantly antagonized suppression of long-term potentiation (LTP) induced by Aβ1-42 in the rat hippocampal CA1 region in vivo. This neuroprotection may be mediated by regulation of calcium homeostasis. Pretreatment with Exendin-4 suppressed Aβ1-42-induced elevation in intracellular calcium concentration ([Ca(2+)]i) through L-type voltage-dependent calcium channels (L-VDCCs) and N-methyl-D-aspartate receptors (NMDARs). Furthermore, Exendin-4 antagonized the decrease in p-Ca(2+)/calmodulin-dependent protein kinase IIα (p-CaMKIIα) induced by Aβ1-42 in the rat hippocampal CA1 region. Thus, the neuroprotective effects of Exendin-4, which likely involve regulation of calcium homeostasis, provide theoretical support for using Exendin-4 to treat and prevent AD in the future.

  9. Evalution of Renal Involvement in Patients with Behçet Disease: Need to be Aware About Potential Hypertension in Long Term Follow Up?

    PubMed Central

    Ozel, Deniz; Ozel, Betul Duran; Ozkan, Fuat; Kutlu, Ramazan

    2016-01-01

    Summary Backround The aim of this study was to evaluate frequency and severity of kidney involvement with some clinical, ultrasonography and color Doppler measurements in patients with Behçet disease. Material/Methods This study was including 32 patients with Behçet disease and 32 healthy sex and age-matched control subjects. Patients were divided into two groups as period of disease 0–6 years and 7 years and above to evaluate effect of duration of disease. We evaluated some biochemical tests in both blood and urine related to renal functions, blood pressure values. Gray scale and color Doppler findings were noted. Results Renal artery volume flow in patients with a duration of 7 years or above was significantly decreased compared to control group (p<0.05). However, gray scale ultrasound and color Doppler measurements reveal there was not statistically significant change compared to control group. There was no biochemical abnormalities in any patient. Four patients had elevated blood pressure but mean blood pressure values were not statistically different compared to volunteers. Conclusions Renal involvement ratios varies in different studies but not common. End stage renal failure can be seen very rare. Furthermore, vasculitic changes can lead renal artery narrowness and can result to decrease in renal blood flow. It has a potential to activate renin angiotensin aldosterone cascade to elevate blood pressure. We must be aware about blood pressure of patients with Behçet disease, especially with long term follow up. PMID:26937259

  10. Exendin-4 antagonizes Aβ1-42-induced suppression of long-term potentiation by regulating intracellular calcium homeostasis in rat hippocampal neurons.

    PubMed

    Wang, Xiaohui; Wang, Li; Jiang, Ruirui; Yuan, Yuan; Yu, Qianqian; Li, Yameng

    2015-11-19

    An imbalance of intracellular calcium homeostasis induced by amyloid β-protein (Aβ) contributes to the pathogenesis of Alzheimer's disease (AD), such as deficits in learning and memory. Therefore, regulation of calcium homeostasis may represent a new strategy for treatment of AD. Growing evidence suggests that type 2 diabetes mellitus (T2DM) and AD are closely related in pathogenesis. Thus, drugs used in treatment of T2DM may modify the pathogenesis of AD. This study demonstrated that Exendin-4, which is a glucagon-like peptide-1 (GLP-1) analog used as a therapeutic drug for T2DM, significantly antagonized suppression of long-term potentiation (LTP) induced by Aβ1-42 in the rat hippocampal CA1 region in vivo. This neuroprotection may be mediated by regulation of calcium homeostasis. Pretreatment with Exendin-4 suppressed Aβ1-42-induced elevation in intracellular calcium concentration ([Ca(2+)]i) through L-type voltage-dependent calcium channels (L-VDCCs) and N-methyl-D-aspartate receptors (NMDARs). Furthermore, Exendin-4 antagonized the decrease in p-Ca(2+)/calmodulin-dependent protein kinase IIα (p-CaMKIIα) induced by Aβ1-42 in the rat hippocampal CA1 region. Thus, the neuroprotective effects of Exendin-4, which likely involve regulation of calcium homeostasis, provide theoretical support for using Exendin-4 to treat and prevent AD in the future. PMID:26390937

  11. Methodological Aspects of the Potential Use of Dendrochronological Techniques When Analyzing the Long-Term Impact of Tourism on Protected Areas.

    PubMed

    Ciapała, Szymon; Adamski, Paweł

    2015-01-01

    Intensification of pedestrian tourism causes damage to trees near tourist tracks, and likewise changes the soil structure. As a result, one may expect that annual amount of trees growing near tracks is significantly lower than deeper in the forest. However, during the study of the long-term impact of tourism on the environment (determined from tree increment dynamics), some methodological problems may occur. It is particularly important in protected areas where law and administrative regulations related to nature conservation force research to be conducted using small samples. In this paper we have analyzed the data collected in the Polish part of the Tatra National Park in the two study plots divided into two zones each: the area directly under the influence of the tourist's trampling and the control group. The aim of such analyses was to present the potential effects of the factors which may affect the results of dendrochronological analysis: (i) small size of samples that affects their representativeness, (ii) spatial differences in the rates of the process, as a result of spatial variability of environmental factors and (iii) temporal differences in the rates of the process. This study confirms that the factors mentioned above could significantly influence the results and should be taken into consideration during the analysis.

  12. Temporal Variation in Honey Production by the Stingless Bee Melipona subnitida (Hymenoptera: Apidae): Long-Term Management Reveals its Potential as a Commercial Species in Northeastern Brazil.

    PubMed

    Koffler, Sheina; Menezes, Cristiano; Menezes, Paulo Roberto; Kleinert, Astrid de Matos Peixoto; Imperatriz-Fonseca, Vera Lucia; Pope, Nathaniel; Jaffé, Rodolfo

    2015-06-01

    Even though stingless beekeeping has a great potential as a sustainable development tool, the activity remains essentially informal, technical knowledge is scarce, and management practices lack the sophistication and standardization found in apiculture. Here, we contributed to the further development of stingless beekeeping by investigating the long-term impact of management and climate on honey production and colony survival in the stingless bee Melipona subnitida Ducke (1910). We analyzed a 10-yr record of 155 M. subnitida colonies kept by a commercial honey producer of northeastern Brazil. This constitutes the longest and most accurate record available for a stingless bee. We modeled honey production in relation to time (years), age, management practices (colony division and food supplementation), and climatic factors (temperature and precipitation), and used a model selection approach to identify which factors best explained honey production. We also modeled colony mortality in relation to climatic factors. Although the amount of honey produced by each colony decreased over time, we found that the probability of producing honey increased over the years. Colony divisions decreased honey production, but did not affect honey presence, while supplementary feeding positively affected honey production. In warmer years, the probability of producing honey decreased and the amount of honey produced was lower. In years with lower precipitation, fewer colonies produced honey. In contrast, colony mortality was not affected by climatic factors, and some colonies lived up to nine years, enduring extreme climatic conditions. Our findings provide useful guidelines to improve management and honey production in stingless bees. PMID:26470204

  13. Adolescent mice show anxiety- and aggressive-like behavior and the reduction of long-term potentiation in mossy fiber-CA3 synapses after neonatal maternal separation.

    PubMed

    Shin, S Y; Han, S H; Woo, R-S; Jang, S H; Min, S S

    2016-03-01

    Exposure to maternal separation (MS) during early life is an identified risk factor for emotional disorders such as anxiety and depression later in life. This study investigated the effects of neonatal MS on the behavior and long-term potentiation (LTP) as well as basic synaptic transmission at hippocampal CA3-CA1 and mossy fiber (MF)-CA3 synapses in adolescent mice for 19days. When mice were adolescents, we measured depression, learning, memory, anxious and aggressive behavior using the forced swimming test (FST), Y-maze, Morris water maze (MWM), elevated plus maze (EPM), three consecutive days of the open field test, the social interaction test, the tube-dominance test and the resident-intruder test. The results showed that there was no difference in FST, Y-maze, and MWM performance. However, MS mice showed more anxiety-like behavior in the EPM test and aggressive-like behavior in the tube-dominance and resident-intruder tests. In addition, the magnitude of LTP and release probability in the MF-CA3 synapses was reduced in the MS group but not in the CA3-CA1 synapse. Our results indicate that early life stress due to MS may induce anxiety- and aggressive-like behavior during adolescence, and these effects are associated with synaptic plasticity at the hippocampal MF-CA3 synapses.

  14. Temporal Variation in Honey Production by the Stingless Bee Melipona subnitida (Hymenoptera: Apidae): Long-Term Management Reveals its Potential as a Commercial Species in Northeastern Brazil.

    PubMed

    Koffler, Sheina; Menezes, Cristiano; Menezes, Paulo Roberto; Kleinert, Astrid de Matos Peixoto; Imperatriz-Fonseca, Vera Lucia; Pope, Nathaniel; Jaffé, Rodolfo

    2015-06-01

    Even though stingless beekeeping has a great potential as a sustainable development tool, the activity remains essentially informal, technical knowledge is scarce, and management practices lack the sophistication and standardization found in apiculture. Here, we contributed to the further development of stingless beekeeping by investigating the long-term impact of management and climate on honey production and colony survival in the stingless bee Melipona subnitida Ducke (1910). We analyzed a 10-yr record of 155 M. subnitida colonies kept by a commercial honey producer of northeastern Brazil. This constitutes the longest and most accurate record available for a stingless bee. We modeled honey production in relation to time (years), age, management practices (colony division and food supplementation), and climatic factors (temperature and precipitation), and used a model selection approach to identify which factors best explained honey production. We also modeled colony mortality in relation to climatic factors. Although the amount of honey produced by each colony decreased over time, we found that the probability of producing honey increased over the years. Colony divisions decreased honey production, but did not affect honey presence, while supplementary feeding positively affected honey production. In warmer years, the probability of producing honey decreased and the amount of honey produced was lower. In years with lower precipitation, fewer colonies produced honey. In contrast, colony mortality was not affected by climatic factors, and some colonies lived up to nine years, enduring extreme climatic conditions. Our findings provide useful guidelines to improve management and honey production in stingless bees.

  15. Expression of p53 Target Genes in the Early Phase of Long-Term Potentiation in the Rat Hippocampal CA1 Area

    PubMed Central

    Pustylnyak, Vladimir O.; Lisachev, Pavel D.; Shtark, Mark B.

    2015-01-01

    Gene expression plays an important role in the mechanisms of long-term potentiation (LTP), which is a widely accepted experimental model of synaptic plasticity. We have studied the expression of at least 50 genes that are transcriptionally regulated by p53, as well as other genes that are related to p53-dependent processes, in the early phase of LTP. Within 30 min after Schaffer collaterals (SC) tetanization, increases in the mRNA and protein levels of Bax, which are upregulated by p53, and a decrease in the mRNA and protein levels of Bcl2, which are downregulated by p53, were observed. The inhibition of Mdm2 by nutlin-3 increased the basal p53 protein level and rescued its tetanization-induced depletion, which suggested the involvement of Mdm2 in the control over p53 during LTP. Furthermore, nutlin-3 caused an increase in the basal expression of Bax and a decrease in the basal expression of Bcl2, whereas tetanization-induced changes in their expression were occluded. These results support the hypothesis that p53 may be involved in transcriptional regulation during the early phase of LTP. We hope that the presented data may aid in the understanding of the contribution of p53 and related genes in the processes that are associated with synaptic plasticity. PMID:25767724

  16. Age-Dependent Switch of the Role of Serotonergic 5-HT1A Receptors in Gating Long-Term Potentiation in Rat Visual Cortex In Vivo

    PubMed Central

    Gagolewicz, Peter J.; Dringenberg, Hans C.

    2016-01-01

    The rodent primary visual cortex (V1) is densely innervated by serotonergic axons and previous in vitro work has shown that serotonin (5-HT) can modulate plasticity (e.g., long-term potentiation (LTP)) at V1 synapses. However, little work has examined the effects of 5-HT on LTP under in vivo conditions. We examined the role of 5-HT on LTP in V1 elicited by theta burst stimulation (TBS) of the lateral geniculate nucleus in urethane-anesthetized (adult and juvenile) rats. Thalamic TBS consistently induced potentiation of field postsynaptic potentials (fPSPs) recorded in V1. While 5-HT application (0.1–10 mM) itself did not alter LTP levels, the broad-acting 5-HT receptor antagonists methiothepin (1 mM) resulted in a clear facilitation of LTP in adult animals, an effect that was mimicked by the selective 5-HT1A receptor antagonist WAY 100635 (1 mM). Interestingly, in juvenile rats, WAY 100635 application inhibited LTP, indicative of an age-dependent switch in the role of 5-HT1A receptors in gating V1 plasticity. Analyses of spontaneous electrocorticographic (ECoG) activity in V1 indicated that the antagonist-induced LTP enhancement was not related to systematic changes in oscillatory activity in V1. Together, these data suggest a facilitating role of 5-HT1A receptor activation on LTP in the juvenile V1, which switches to a tonic, inhibitory influence in adulthood. PMID:27247804

  17. Neurotoxicity of developmental hypothyroxinemia and hypothyroidism in rats: Impairments of long-term potentiation are mediated by phosphatidylinositol 3-kinase signaling pathway

    SciTech Connect

    Wang, Yi; Wei, Wei; Wang, Yuan; Dong, Jing; Song, Binbin; Min, Hui; Teng, Weiping; Chen, Jie

    2013-09-01

    Neurotoxicity of iodine deficiency-induced hypothyroidism during developmental period results in serious impairments of brain function, such as learning and memory. These impairments are largely irreversible, and the underlying mechanisms remain unclear. In addition to hypothyroidism, iodine deficiency may cause hypothyroxinemia, a relatively subtle form of thyroid hormone deficiency. Neurotoxicity of developmental hypothyroxinemia also potentially impairs learning and memory. However, more direct evidence of the associations between developmental hypothyroxinemia and impairments of learning and memory should be provided, and the underlying mechanisms remain to be elucidated. Thus, in the present study, we investigated the effects of developmental hypothyroxinemia and hypothyroidism on long-term potentiation (LTP), a widely accepted cellular model of learning and memory, in the hippocampal CA1 region. The activation of the phosphatidylinositol 3-kinase (PI3K) signaling pathway – a pathway closely associated with synaptic plasticity and learning and memory – was also investigated. Wistar rats were treated with iodine deficient diet or methimazole (MMZ) to induce developmental hypothyroxinemia or hypothyroidism. The results showed that developmental hypothyroxinemia caused by mild iodine deficiency and developmental hypothyroidism caused by severe iodine deficiency or MMZ significantly reduced the field-excitatory postsynaptic potential (f-EPSP) slope and the population spike (PS) amplitude. Decreased activation of the PI3K signaling pathway was also observed in rats subjected to developmental hypothyroxinemia or hypothyroidism. Our results may support the hypothesis that neurotoxicity of both developmental hypothyroxinemia and hypothyroidism causes damages to learning and memory. Our results also suggest that decreased activation of the PI3K signaling pathway may contribute to impairments of LTP caused by neurotoxicity of both developmental hypothyroxinemia and

  18. α1-Adrenoceptors in the hippocampal dentate gyrus involved in learning-dependent long-term potentiation during active-avoidance learning in rats.

    PubMed

    Lv, Jing; Zhan, Su-Yang; Li, Guang-Xie; Wang, Dan; Li, Ying-Shun; Jin, Qing-Hua

    2016-11-01

    The hippocampus is the key structure for learning and memory in mammals and long-term potentiation (LTP) is an important cellular mechanism responsible for learning and memory. The influences of norepinephrine (NE) on the modulation of learning and memory, as well as LTP, through β-adrenoceptors are well documented, whereas the role of α1-adrenoceptors in learning-dependent LTP is not yet clear. In the present study, we measured extracellular concentrations of NE in the hippocampal dentate gyrus (DG) region using an in-vivo brain microdialysis and high-performance liquid chromatography techniques during the acquisition and extinction of active-avoidance behavior in freely moving conscious rats. Next, the effects of prazosin (an antagonist of α1-adrenoceptor) and phenylephrine (an agonist of the α1-adrenoceptor) on amplitudes of field excitatory postsynaptic potential were measured in the DG region during the active-avoidance behavior. Our results showed that the extracellular concentration of NE in the DG was significantly increased during the acquisition of active-avoidance behavior and gradually returned to the baseline level following extinction training. A local microinjection of prazosin into the DG significantly accelerated the acquisition of the active-avoidance behavior, whereas a local microinjection of phenylephrine retarded the acquisition of the active-avoidance behavior. Furthermore, in all groups, the changes in field excitatory postsynaptic potential amplitude were accompanied by corresponding changes in active-avoidance behavior. Our results suggest that NE activation of α1-adrenoceptors in the hippocampal DG inhibits active-avoidance learning by modulation of synaptic efficiency in rats.

  19. Neurotoxicity of developmental hypothyroxinemia and hypothyroidism in rats: Impairments of long-term potentiation are mediated by phosphatidylinositol 3-kinase signaling pathway.

    PubMed

    Wang, Yi; Wei, Wei; Wang, Yuan; Dong, Jing; Song, Binbin; Min, Hui; Teng, Weiping; Chen, Jie

    2013-09-01

    Neurotoxicity of iodine deficiency-induced hypothyroidism during developmental period results in serious impairments of brain function, such as learning and memory. These impairments are largely irreversible, and the underlying mechanisms remain unclear. In addition to hypothyroidism, iodine deficiency may cause hypothyroxinemia, a relatively subtle form of thyroid hormone deficiency. Neurotoxicity of developmental hypothyroxinemia also potentially impairs learning and memory. However, more direct evidence of the associations between developmental hypothyroxinemia and impairments of learning and memory should be provided, and the underlying mechanisms remain to be elucidated. Thus, in the present study, we investigated the effects of developmental hypothyroxinemia and hypothyroidism on long-term potentiation (LTP), a widely accepted cellular model of learning and memory, in the hippocampal CA1 region. The activation of the phosphatidylinositol 3-kinase (PI3K) signaling pathway - a pathway closely associated with synaptic plasticity and learning and memory - was also investigated. Wistar rats were treated with iodine deficient diet or methimazole (MMZ) to induce developmental hypothyroxinemia or hypothyroidism. The results showed that developmental hypothyroxinemia caused by mild iodine deficiency and developmental hypothyroidism caused by severe iodine deficiency or MMZ significantly reduced the field-excitatory postsynaptic potential (f-EPSP) slope and the population spike (PS) amplitude. Decreased activation of the PI3K signaling pathway was also observed in rats subjected to developmental hypothyroxinemia or hypothyroidism. Our results may support the hypothesis that neurotoxicity of both developmental hypothyroxinemia and hypothyroidism causes damages to learning and memory. Our results also suggest that decreased activation of the PI3K signaling pathway may contribute to impairments of LTP caused by neurotoxicity of both developmental hypothyroxinemia and

  20. α1-Adrenoceptors in the hippocampal dentate gyrus involved in learning-dependent long-term potentiation during active-avoidance learning in rats.

    PubMed

    Lv, Jing; Zhan, Su-Yang; Li, Guang-Xie; Wang, Dan; Li, Ying-Shun; Jin, Qing-Hua

    2016-11-01

    The hippocampus is the key structure for learning and memory in mammals and long-term potentiation (LTP) is an important cellular mechanism responsible for learning and memory. The influences of norepinephrine (NE) on the modulation of learning and memory, as well as LTP, through β-adrenoceptors are well documented, whereas the role of α1-adrenoceptors in learning-dependent LTP is not yet clear. In the present study, we measured extracellular concentrations of NE in the hippocampal dentate gyrus (DG) region using an in-vivo brain microdialysis and high-performance liquid chromatography techniques during the acquisition and extinction of active-avoidance behavior in freely moving conscious rats. Next, the effects of prazosin (an antagonist of α1-adrenoceptor) and phenylephrine (an agonist of the α1-adrenoceptor) on amplitudes of field excitatory postsynaptic potential were measured in the DG region during the active-avoidance behavior. Our results showed that the extracellular concentration of NE in the DG was significantly increased during the acquisition of active-avoidance behavior and gradually returned to the baseline level following extinction training. A local microinjection of prazosin into the DG significantly accelerated the acquisition of the active-avoidance behavior, whereas a local microinjection of phenylephrine retarded the acquisition of the active-avoidance behavior. Furthermore, in all groups, the changes in field excitatory postsynaptic potential amplitude were accompanied by corresponding changes in active-avoidance behavior. Our results suggest that NE activation of α1-adrenoceptors in the hippocampal DG inhibits active-avoidance learning by modulation of synaptic efficiency in rats. PMID:27603730

  1. The role of BRAF V600E mutation as a potential marker for prognostic stratification of papillary thyroid carcinoma: a long-term follow-up study.

    PubMed

    Daliri, Mahdi; Abbaszadegan, Mohammad Reza; Bahar, Mostafa Mehrabi; Arabi, Azadeh; Yadollahi, Mona; Ghafari, Azar; Taghehchian, Negin; Zakavi, Seyed Rasoul

    2014-01-01

    Abstract Papillary carcinoma is the most prevalent malignancy of thyroid gland, and its incidence has been recently increased. The BRAF(V600E) mutation is the most frequent genetic alteration in papillary thyroid carcinoma (PTC). The role of BRAF(V600E) mutation as a potential prognostic factor has been controversially reported in different studies, with short-term follow-up. In this study, we evaluated the role of BRAF(V600E) mutation as a potential marker for prognostic stratification of patients with PTC in long-term follow-up. We studied 69 PTC patients with a mean follow-up period of 63.9 months (median: 60 m). The BRAF(V600E) mutation was analyzed by PCR-single-strand conformational polymorphism and sequencing. The correlation between the presence or absence of the BRAF(V600E) mutation, clinicopathological features and prognosis of PTC patients were studied. The BRAF(V600E) mutation was found in 28 of 69 (40.6%) PTC patients, and it was significantly more frequent in older patients (p < 0.001), in advanced tumor stages (p = 0.006) and in patients with history of radiation exposure (p = 0.037). Incomplete response to treatment in PTC patients was significantly correlated with certain clinicopathological characteristics (follow-up time, distant metastases, advanced stage, first thyroglobulin (fTg) level, history of reoperation and external radiotherapy and delay in iodine therapy) but it was not related to the presence of BRAF(V600E) mutation. Prevalence of BRAF(V600E) mutation was 40.6% in patients with papillary thyroid cancer in northeast of Iran. The BRAF(V600E) mutation was associated with older age and advanced tumor stage but was not correlated with incomplete response during follow-up.

  2. IN VIVO EVALUATION OF SKIN IRRITATION POTENTIAL, MELASMA AND SEBUM CONTENT FOLLOWING LONG TERM APPLICATION OF SKIN CARE CREAM IN HEALTHY ADULTS, USING NON-INVASIVE BIOMETROLOGICAL TECHNIQUES.

    PubMed

    Arshad, Atif I; Khan, Shoaib H M; Akhtar, Naveed; Mahmood, Asif; Sarfraz, Rai Muhammad

    2016-01-01

    The present investigation was conducted to evaluate non-invasively, various functional skin parameters i.e., irritation potential, melasma and sebum contents following long term application of topical cream (w/o) loaded with 2% methanolic extract of Ananas comosus L. versus placebo control (base) in healthy adults. Healthy human volunteers (n = 11, aged 20-30 years) were recruited for investigation and written informed consent was taken from each volunteer. In this single blinded study every volunteer applied formulation on one side of face and placebo on the other side of face twice daily for a period of 12 weeks (three months). Different skin parameters i.e., skin irritancy, melasma, and sebum contents were measured on both sides of face at baseline and after two weeks interval, using photometric device Mexameter and Sebumeter in a draught free room with modulated conditions of temperature (22-25°C) and humidity (55-60%). It was evident from the results that no primary skin irritancy was observed with patch test. Besides, statistical interpretation indicates that treatment with formulation is superior to placebo because it significantly (p ≤ 0.05) reduced the skin irritancy, melasma and sebum secretions throughout the study and reaching maximum -20.76 ± 0.89, -54.2 ± 0.37 and -40.71 ± 0.75%, respectively, at the end of study period. Antioxidant activity of extract was 92% compared to standard antioxidant. Conclusively, active cream loaded with fruit extract was well tolerated by all the volunteers and suitable to treat contact dermatitis, greasy skin, acne and seborrheic dermatitis and augmenting beauty and attraction by depigmentation of human skin. So, in the future, there is need to clinically evaluate these formulations in patients with compromised skin functions i.e., contact dermatitis, melasma, and acne vulgaris in order to explore the actual potential of this fruit. PMID:27008816

  3. IN VIVO EVALUATION OF SKIN IRRITATION POTENTIAL, MELASMA AND SEBUM CONTENT FOLLOWING LONG TERM APPLICATION OF SKIN CARE CREAM IN HEALTHY ADULTS, USING NON-INVASIVE BIOMETROLOGICAL TECHNIQUES.

    PubMed

    Arshad, Atif I; Khan, Shoaib H M; Akhtar, Naveed; Mahmood, Asif; Sarfraz, Rai Muhammad

    2016-01-01

    The present investigation was conducted to evaluate non-invasively, various functional skin parameters i.e., irritation potential, melasma and sebum contents following long term application of topical cream (w/o) loaded with 2% methanolic extract of Ananas comosus L. versus placebo control (base) in healthy adults. Healthy human volunteers (n = 11, aged 20-30 years) were recruited for investigation and written informed consent was taken from each volunteer. In this single blinded study every volunteer applied formulation on one side of face and placebo on the other side of face twice daily for a period of 12 weeks (three months). Different skin parameters i.e., skin irritancy, melasma, and sebum contents were measured on both sides of face at baseline and after two weeks interval, using photometric device Mexameter and Sebumeter in a draught free room with modulated conditions of temperature (22-25°C) and humidity (55-60%). It was evident from the results that no primary skin irritancy was observed with patch test. Besides, statistical interpretation indicates that treatment with formulation is superior to placebo because it significantly (p ≤ 0.05) reduced the skin irritancy, melasma and sebum secretions throughout the study and reaching maximum -20.76 ± 0.89, -54.2 ± 0.37 and -40.71 ± 0.75%, respectively, at the end of study period. Antioxidant activity of extract was 92% compared to standard antioxidant. Conclusively, active cream loaded with fruit extract was well tolerated by all the volunteers and suitable to treat contact dermatitis, greasy skin, acne and seborrheic dermatitis and augmenting beauty and attraction by depigmentation of human skin. So, in the future, there is need to clinically evaluate these formulations in patients with compromised skin functions i.e., contact dermatitis, melasma, and acne vulgaris in order to explore the actual potential of this fruit.

  4. Comparative Analysis of Short- and Long-Term Changes in Gene Expression Caused by Low Water Potential in Potato (Solanum tuberosum) Cell-Suspension Cultures.

    PubMed

    Leone, A.; Costa, A.; Tucci, M.; Grillo, S.

    1994-10-01

    To dissect the cellular response to water stress and compare changes induced as a generalized response with those involved in tolerance/acclimation mechanisms, we analyzed changes in two-dimensional electrophoretic patterns of in vivo [35S]methionine-labeled polypeptides of cultured potato (Solanum tuberosum) cells after gradual and long exposure to polyethylene glycol (PEG)- mediated low water potential versus those induced in cells abruptly exposed to the same stress intensity. Protein synthesis was not inhibited by gradual stress imposition, and the expression of 17 proteins was induced in adapted cells. Some polypeptides were inducible under mild stress conditions (5% PEG) and accumulated further when cells were exposed to a higher stress intensity (10 and 20% PEG). The synthesis of another set of polypeptides was up-regulated only when more severe water-stress conditions were applied, suggesting that plant cells were able to monitor different levels of stress intensity and modulate gene expression accordingly. In contrast, in potato cells abruptly exposed to 20% PEG, protein synthesis was strongly inhibited. Nevertheless, a large set of polypeptides was identified whose expression was increased. Most of these polypeptides were not induced in adapted cells, but many of them were common to those observed in abscisic acid (ABA)-treated cells. These data, along with the finding that cellular ABA content increased in PEG-shocked cells but not in PEG-adapted cells, suggested that this hormone is mainly involved in the rapid response to stress rather than long-term adaptation. A further group of proteins included those induced after long exposure to both water stress and shock. Western blot analysis revealed that osmotin was one protein belonging to this common group. This class may represent induced proteins that accumulate specifically in response to low water potential and that are putatively involved in the maintenance of cellular homeostasis under prolonged

  5. The Contribution of Spatial and Temporal Molecular Networks in the Induction of Long-term Memory and Its Underlying Synaptic Plasticity

    PubMed Central

    Mirisis, Anastasios A.; Alexandrescu, Anamaria; Carew, Thomas J.; Kopec, Ashley M.

    2016-01-01

    The ability to form long-lasting memories is critical to survival and thus is highly conserved across the animal kingdom. By virtue of its complexity, this same ability is vulnerable to disruption by a wide variety of neuronal traumas and pathologies. To identify effective therapies with which to treat memory disorders, it is critical to have a clear understanding of the cellular and molecular mechanisms which subserve normal learning and memory. A significant challenge to achieving this level of understanding is posed by the wide range of distinct temporal and spatial profiles of molecular signaling induced by learning-related stimuli. In this review we propose that a useful framework within which to address this challenge is to view the molecular foundation of long-lasting plasticity as composed of unique spatial and temporal molecular networks that mediate signaling both within neurons (such as via kinase signaling) as well as between neurons (such as via growth factor signaling). We propose that evaluating how cells integrate and interpret these concurrent and interacting molecular networks has the potential to significantly advance our understanding of the mechanisms underlying learning and memory formation.

  6. Genetic knockout of the α7 nicotinic acetylcholine receptor gene alters hippocampal long-term potentiation in a background strain-dependent manner.

    PubMed

    Freund, Ronald K; Graw, Sharon; Choo, Kevin S; Stevens, Karen E; Leonard, Sherry; Dell'Acqua, Mark L

    2016-08-01

    Reduced α7 nicotinic acetylcholine receptor (nAChR) function is linked to impaired hippocampal-dependent sensory processing and learning and memory in schizophrenia. While knockout of the Chrna7 gene encoding the α7nAChR on a C57/Bl6 background results in changes in cognitive measures, prior studies found little impact on hippocampal synaptic plasticity in these mice. However, schizophrenia is a multi-genic disorder where complex interactions between specific genetic mutations and overall genetic background may play a prominent role in determining phenotypic penetrance. Thus, we compared the consequences of knocking out the α7nAChR on synaptic plasticity in C57/Bl6 and C3H mice, which differ in their basal α7nAChR expression levels. Homozygous α7 deletion in C3H mice, which normally express higher α7nAChR levels, resulted in impaired long-term potentiation (LTP) at hippocampal CA1 synapses, while C3H α7 heterozygous mice maintained robust LTP. In contrast, homozygous α7 deletion in C57 mice, which normally express lower α7nAChR levels, did not alter LTP, as had been previously reported for this strain. Thus, the threshold of Chrna7 expression required for LTP may be different in the two strains. Measurements of auditory gating, a hippocampal-dependent behavioral paradigm used to identify schizophrenia-associated sensory processing deficits, was abnormal in C3H α7 knockout mice confirming that auditory gating also requires α7nAChR expression. Our studies highlight the importance of genetic background on the regulation of synaptic plasticity and could be relevant for understanding genetic and cognitive heterogeneity in human studies of α7nAChR dysfunction in mental disorders.

  7. Inhibition of the Motor Protein Eg5/Kinesin-5 in Amyloid β-Mediated Impairment of Hippocampal Long-Term Potentiation and Dendritic Spine Loss.

    PubMed

    Freund, Ronald K; Gibson, Emily S; Potter, Huntington; Dell'Acqua, Mark L

    2016-05-01

    Alzheimer's disease (AD) is characterized by neurofibrillary tangles, amyloid plaques, and neurodegeneration. However, this pathology is preceded by increased soluble amyloid beta (Aβ) 1-42 oligomers that interfere with the glutamatergic synaptic plasticity required for learning and memory, includingN-methyl-d-aspartate receptor (NMDAR)-dependent long-term potentiation (LTP). In particular, soluble Aβ(1-42) acutely inhibits LTP and chronically causes synapse loss. Many mechanisms have been proposed for Aβ-induced synaptic dysfunction, but we recently found that Aβ(1-42) inhibits the microtubule motor protein Eg5/kinesin-5. Here we compared the impacts of Aβ(1-42) and monastrol, a small-molecule Eg5 inhibitor, on LTP in hippocampal slices and synapse loss in neuronal cultures. Acute (20-minute) treatment with monastrol, like Aβ, completely inhibited LTP at doses >100 nM. In addition, 1 nM Aβ(1-42) or 50 nM monastrol inhibited LTP #x223c;50%, and when applied together caused complete LTP inhibition. At concentrations that impaired LTP, neither Aβ(1-42) nor monastrol inhibited NMDAR synaptic responses until #x223c;60 minutes, when only #x223c;25% inhibition was seen for monastrol, indicating that NMDAR inhibition was not responsible for LTP inhibition by either agent when applied for only 20 minutes. Finally, 48 hours of treatment with either 0.5-1.0μM Aβ(1-42) or 1-5μM monastrol reduced the dendritic spine/synapse density in hippocampal cultures up to a maximum of #x223c;40%, and when applied together at maximal concentrations, no additional spine loss resulted. Thus, monastrol can mimic and in some cases occlude the impact of Aβon LTP and synapse loss, suggesting that Aβinduces acute and chronic synaptic dysfunction in part through inhibiting Eg5.

  8. Investigating the potential for long-term permeable reactive barrier (PRB) monitoring from the electrical signatures associated with the reduction in reactive iron performance

    SciTech Connect

    Slater, Lee D.; Korte, N.; Baker, J.

    2005-12-14

    The objective of this work was to conduct laboratory and field experiments to determine the sensitivity of low frequency electrical measurements (resistivity and induced polarization) to the processes of corrosion and precipitation that are believed to limit permeable reactive barrier (PRB) performance. The research was divided into four sets of experiments that were each written up and submitted to a peer-reviewed journal: [1] A laboratory experiment to define the controls of aqueous chemistry (electrolyte activity; pH; valence) and total zero valent iron (Fe0) available surface area on the electrical properties of Fe0 columns. [2] A laboratory experiment to determine the impact of corrosion and precipitation on the electrical response of synthetic Fe0 columns as a result of geochemical reactions with NaSO4 and NaCO3 electrolytes. [3] Laboratory experiments on a sequence of cores retrieved from the Kansas City PRB to determine the magnitude of electrical and geochemical changes within a field active PRB after eight years of operation [4] Field-scale cross borehole resistivity and induced polarization monitoring of the Kansas City PRB to evaluate the potential of electrical imaging as a technology for non-invasive, long-term monitoring of indicators of reduced PRB performance This report first summarizes the findings of the four major experiments conducted under this research. The reader is referred to the four papers in Appendices 1-4 for a full description of each experiment, including motivation and significance, technical details, findings and implications. The deliverables of the project, including the publications, conference papers and new collaborative arrangements that have resulted are then described. Appendices 5-6 contain two technical reports written by co-PI Korte describing (1) supporting geochemical measurements, and (2) the coring procedure, conducted at the Kansas City PRB as part of this project.

  9. Test-Retest Reliability of 10 Hz Conditioning Electrical Stimulation Inducing Long-Term Potentiation (LTP)-Like Pain Amplification in Humans

    PubMed Central

    Xia, Weiwei; Mørch, Carsten Dahl; Andersen, Ole Kæseler

    2016-01-01

    Background 10 Hz conditioning electrical stimulation (CES) has been shown to induce long-term potentiation (LTP)-like pain amplification similar to traditional 100 Hz CES in healthy humans. The aim of this study was to assess the test-retest reliability and to estimate sample sizes required for future crossover and parallel study designs. Methods The 10 Hz paradigm (500 rectangular pulses lasting 50 s) was repeated on two separate days with one week interval in twenty volunteers. Perceptual intensities to single electrical stimulation (SES) at the conditioned skin site and to mechanical stimuli (pinprick and light stroking) in immediate vicinity to the conditioned skin site were recorded. Superficial blood flow (SBF) was assessed as indicator of neurogenic inflammation. All outcome measures were assessed with 10 min interval three times before and six times after the CES. The coefficient of variation and intra-class correlation coefficient were calculated within session and between sessions. Sample sizes were estimated for future crossover (Ncr) and parallel (Np) drug testing studies expected to detect a 30% decrease for the individual outcome measure following 10 Hz CES. Results Perceptual intensity ratings to light stroking (Ncr = 2, Np = 33) and pinprick stimulation (491 mN) (Ncr = 6, Np = 54) increased after CES and showed better reliability in crossover than parallel design. The SBF increased after CES, and then declined until reaching a plateau 20 minutes postCES. SBF showed acceptable reliability both in crossover and parallel designs (Ncr = 3, Np = 13). Pain ratings to SES were reliable, but with large estimated sample sizes (Ncr = 634, Np = 11310) due to the minor pain amplification. Conclusions The reliability of 10 Hz CES was acceptable in inducing LTP-like effects in the assessments of superficial blood flow, heterotopic mechanical hyperalgesia, and dysesthesia in terms of sample sizes for future crossover study designs. PMID:27529175

  10. Long-term reindeer grazing limits warming-induced increases in CO2 released by tundra heath soil: potential role of soil C quality

    NASA Astrophysics Data System (ADS)

    Väisänen, Maria; Sjögersten, Sofie; Large, David; Drage, Trevor; Stark, Sari

    2015-09-01

    The current climate warming in the Arctic may increase the microbial degradation of vast pools of soil carbon (C); however, the temperature sensitivity of decomposition is often highly dependent on the quality of accumulated soil C. Grazing by reindeer (Rangifer tarandus L.) substantially affects the dominant vegetation and often increases graminoids in relation to dwarf shrubs in ecosystems, but the effect of this vegetation shift on the soil C quality has not been previously investigated. We analyzed the soil C quality and rate of microbially mediated CO2 release at different temperatures in long-term laboratory incubations using soils from lightly grazed dwarf shrub-dominated and heavily grazed graminoid-dominated tundra ecosystem. The soil C quality was characterized by solid-state cross-polarization magic angle spinning (CPMAS 13C NMR) spectroscopy, which showed a higher relative proportion of carbohydrate C under light grazing and higher relative proportion of aliphatic not-O-substituted C under heavy grazing. Initial measurements showed lower temperature sensitivity of the CO2 release in soils under light grazing compared with soil under heavy grazing, but the overall CO2 release rate and its temperature sensitivity increased under light grazing as the soil incubation progressed. At the end of incubation, significantly more carbohydrate C had been lost in soils under light grazing compared with heavy grazing. These findings indicate that there may be a link between the grazer-induced effects on soil C quality and the potential of soils to release CO2 to atmosphere. We suggest that vegetation shifts induced by grazing could influence the proportion of accumulated soil C that is vulnerable to microbial degradation under warming climate.

  11. Decreased striatal dopamine release underlies increased expression of long-term synaptic potentiation at corticostriatal synapses 24 hours after 3-nitropropionic acid induced chemical hypoxia

    PubMed Central

    Akopian, Garnik; Crawford, Cynthia; Beal, M. Flint; Cappelletti, Maurand; Jakowec, Michael W.; Petzinger, Giselle M.; Zheng, Ling; Gheorghe, Stacey L.; Reichel, Carmela M.; Chow, Robert; Walsh, John P

    2008-01-01

    The striatum is particularly sensitive to the irreversible inhibitor of succinate dehyrdrogenase 3-nitropropionic acid (3-NP). In the present study we examined early changes in behavior and dopamine and glutamate synaptic physiology created by a single systemic injection of 3-NP in Fischer 344 rats. Hind limb dystonia was seen 2 hours after 3-NP injections and rats performed poorly on balance beam and rota-rod motor tests 24 hours later. Systemic 3-NP increased NMDA receptor-dependent long-term potentiation (LTP) at corticostriatal synapses over the same time period. The 3-NP induced corticostriatal LTP was not due to increased NMDA receptor number or function, since 3-NP did not change MK-801 binding or NMDA/AMPA receptor current ratios. The LTP seen 24 hours after 3-NP was D1 receptor-dependent and reversed by exogenous addition of dopamine or a D2 receptor agonist to brain slices. High performance liquid chromatography and fast scan cyclic voltammetry revealed a decrease in dopamine content and release in rats injected 24 hours earlier with 3-NP, and much like the enhanced LTP, dopamine changes were reversed by 48 hours. Tyrosine hydroxylase expression was not changed and there was no evidence of striatal cell loss at 24–48 hours after 3-NP exposure. Sprague-Dawley rats showed similar physiological responses to systemic 3-NP, albeit with reduced sensitivity. Thus, 3-NP causes significant changes in motor behavior marked by parallel changes in striatal dopamine release and corticostriatal synaptic plasticity. PMID:18799690

  12. Long-term environmental stewardship.

    SciTech Connect

    Nagy, Michael David

    2010-08-01

    The purpose of this Supplemental Information Source Document is to effectively describe Long-Term Environmental Stewardship (LTES) at Sandia National Laboratories/New Mexico (SNL/NM). More specifically, this document describes the LTES and Long-Term Stewardship (LTS) Programs, distinguishes between the LTES and LTS Programs, and summarizes the current status of the Environmental Restoration (ER) Project.

  13. Influence of climate, fire severity and forest mortality on predictions of long term streamflow: Potential effect of the 2009 wildfire on Melbourne's water supply catchments

    NASA Astrophysics Data System (ADS)

    Feikema, Paul M.; Sherwin, Christopher B.; Lane, Patrick N. J.

    2013-04-01

    SummaryIn February 2009, wildfire affected nine catchments, or approximately 28% of forested catchment area that supplies water to the city of Melbourne, Australia. This has potential to significantly affect the long term water use of these Eucalyptus forests and the consequential water yield because of the ecohydrologic response of some eucalypt species. Approximately 11% of the catchment area was severely burnt by intense fire, where vegetation mortality is higher. Catchment scale models using a physically-based approach were developed for the fire-affected water supply catchments. Different inputs of climate and forest mortality after fire were used to examine the relative contributions of rainfall, fire severity, forest type and forest age on post-fire streamflow. Simulations show the effect of fire on long term streamflow is likely to depend on a number of factors, the relative influence of which changes as rainfall becomes more limiting. Under average rainfall conditions, total reduction in post-fire streamflow after 100 years estimated to be between 1.4% (˜12 GL year-1) and 2.8% (˜24 GL year-1) are an order of magnitude lower than reductions in total catchment inflow during the period of low rainfall between 1997 and 2009, in which reservoir inflow was reduced by nearly 37%. The main reasons for the lower than expected changes in water yield are that a lower proportion of the catchments were affected by severe fire, and so mortality within the fire area was relatively low, and that the average age of the forest canopy (93 years) is younger than what is generally considered old growth forest. This means that the baseline (no-fire) streamflow used for reference is lower than would be expected with older, mature forest. The greatest post-fire affect on total water yield was predicted for the O'Shannassy catchment. This is due to the average forest age, which is the oldest of any of the catchments, that it has the highest average rainfall (1680 mm year-1), and

  14. Erection capability is potentiated by long-term sildenafil treatment: role of blood flow-induced endothelial nitric-oxide synthase phosphorylation.

    PubMed

    Musicki, Biljana; Champion, Hunter C; Becker, Robyn E; Liu, Tongyun; Kramer, Melissa F; Burnett, Arthur L

    2005-07-01

    Despite demonstrated clinical efficacy of sildenafil for the temporary treatment of erectile dysfunction, the possibility that sildenafil used long-term durably augments erectile ability remains unclear. We investigated whether continuous long-term administration of sildenafil at clinically relevant levels to aged rats "primes" the penis for improved erectile ability and involves nitric oxide (NO) or RhoA/Rho-kinase signaling pathways. In aged, but not young rats, sildenafil prolonged erection and increased the protein expressions of phosphorylated endothelial NO synthase (eNOS) at serine-1177 and phosphorylated Akt at serine-473 in penes. Only in the young rat penis, protein expressions of phosphodiesterase-5 and phosphomyosin phosphatase target subunit 1, a marker of Rho-kinase activity, were increased by sildenafil. Sildenafil inhibited phosphodiesterase-5 activity in penes of young and aged rats coincident with assayed free plasma levels of the drug equivalent to clinically therapeutic measurements. We conclude that erectile ability can be enhanced under preconditions of erectile impairment by long-term inhibition of phosphodiesterase-5 and that the effect is mediated by Akt-dependent eNOS phosphorylation. The lack of erectile ability enhancement in young rats by long-term phosphodiesterase-5 inhibition may relate to restrained NO signaling by phosphodiesterase-5 up-regulation, lack of incremental Akt and eNOS phosphorylation, and heightened Rho-kinase signaling in the penis. PMID:15851653

  15. Understanding the potential impact of climate change on long term soil carbon dynamics in tropical cropping systems - evidence from West Africa

    NASA Astrophysics Data System (ADS)

    Cretenet, Michel; Tittonell, Pablo; Guibert, Herve

    2010-05-01

    Long term experiments offer a unique opportunity to assess sustainability and temporal dynamics of biogeochemical cycles in agriculture, as well as the gradual impact on these of relatively slow processes such as climate change. Two long term experiments on annual cropping systems representing locally common crop rotations and cultural practices were established on two contrasting agroecological zones in Ivory Coast (in 1971) and in Mali (in 1965). These experiments were designed to assess the long-term productivity of these systems under different organic matter and nutrient management regimes, applying organic and mineral soil amendments alone or in combination. Organic soil amendments - such as animal manure, compost or plant material collected from the surroundings - were included in the experiments with the double purpose of adding nutrients for immediate crop production and adding organic matter inputs to the soil to restore (or maintain) its organic C content. Here, we provide an overview of the major trends in crop productivity and soil organic C observed in these experiments that illustrates the potential impact of climate change on the effectiveness of different measures to sustain agricultural productivity. Materials and methods Both experiments compared crop productivity on control plots without any soil amendment versus plots receiving organic matter, mineral fertilisers or both combined. The experiment at Gagnoa (southern Ivory Coast) was conducted during 23 years in a zone characterised by a bimodal rainfall regime (c. 1300 mm year-1) that allows two cropping seasons per year (Alfisols 15% clay). Every year maize was planted during the first rainy season. Organic matter was added as compost at a rate of 10 t ha-1 year-1, with or without application of 160 kg N ha-1 year-1 in mineral fertiliser (Chabalier, 1986). The experiment at N'Tarla (southern Mali) was conducted during 24 years in a zone of mono-modal rainfall (c. 900 mm year-1); Alfisols 5

  16. Understanding the potential impact of climate change on long term soil carbon dynamics in tropical cropping systems - evidence from West Africa

    NASA Astrophysics Data System (ADS)

    Cretenet, Michel; Tittonell, Pablo; Guibert, Herve

    2010-05-01

    Long term experiments offer a unique opportunity to assess sustainability and temporal dynamics of biogeochemical cycles in agriculture, as well as the gradual impact on these of relatively slow processes such as climate change. Two long term experiments on annual cropping systems representing locally common crop rotations and cultural practices were established on two contrasting agroecological zones in Ivory Coast (in 1971) and in Mali (in 1965). These experiments were designed to assess the long-term productivity of these systems under different organic matter and nutrient management regimes, applying organic and mineral soil amendments alone or in combination. Organic soil amendments - such as animal manure, compost or plant material collected from the surroundings - were included in the experiments with the double purpose of adding nutrients for immediate crop production and adding organic matter inputs to the soil to restore (or maintain) its organic C content. Here, we provide an overview of the major trends in crop productivity and soil organic C observed in these experiments that illustrates the potential impact of climate change on the effectiveness of different measures to sustain agricultural productivity. Materials and methods Both experiments compared crop productivity on control plots without any soil amendment versus plots receiving organic matter, mineral fertilisers or both combined. The experiment at Gagnoa (southern Ivory Coast) was conducted during 23 years in a zone characterised by a bimodal rainfall regime (c. 1300 mm year-1) that allows two cropping seasons per year (Alfisols 15% clay). Every year maize was planted during the first rainy season. Organic matter was added as compost at a rate of 10 t ha-1 year-1, with or without application of 160 kg N ha-1 year-1 in mineral fertiliser (Chabalier, 1986). The experiment at N'Tarla (southern Mali) was conducted during 24 years in a zone of mono-modal rainfall (c. 900 mm year-1); Alfisols 5

  17. Effects of long-term in vitro culturing of transgenic bovine donor fibroblasts on cell viability and in vitro developmental potential after nuclear transfer.

    PubMed

    Bressan, F F; Miranda, M S; Bajgelman, M C; Perecin, F; Mesquita, L G; Fantinato-Neto, P; Merighe, G F K; Strauss, B E; Meirelles, F V

    2013-04-01

    SCNT experiments, no difference was observed between groups reconstructed with early or late-passage cells when fusion (63.1% and 49%), cleavage (67.7% and 69.9%), eight-cell embryo (36.4% and 44.4%) and blastocyst (21.6% and 20.8%) rates were compared. In conclusion, culture behavior was different between control and eGFP cells. However, when different in vitro culturing periods were compared, long-term cultured transgenic fetal fibroblasts remained competent for blastocyst production when used as nuclei donors in the nuclear transfer technique, a feature needed for the genetic manipulation of cell culture experiments aiming for transgenic animal production.

  18. Short-term facilitation evoked during brief afferent tetani is not altered by long-term potentiation in the guinea-pig hippocampal CA1 region.

    PubMed

    Pananceau, M; Chen, H; Gustafsson, B

    1998-04-15

    1. The aim was to examine whether long-term potentiation (LTP) had effects on short-term synaptic plasticity outside those predicted from its effect on single volley-induced responses. Field recordings from the CA1 region of guinea-pig hippocampal slices were used, and short- term plasticity was evoked by five-impulse trains of 20 and 50 Hz. 2. The five-impulse trains were evoked in the presence of D(-)-2-amino-5-phosphonopentanoic acid (D-AP5; 20-50 microM), picrotoxin (100 microM), and 2-OH-saclofen (200 microM), and care was taken to avoid initiation of postsynaptic spike activation. Field responses were thus considered to reflect non-NMDA receptor-mediated activity only, and demonstrated a net facilitation during the trains. 3. The facilitation was found, on average, to be unaffected by LTP, evoked by strong afferent tetanization. This was true also when release probability had been altered either by the adenosine agonist N-cyclohexyladenosine (CHA; 100 nM) or the antagonist 8-cyclopentyl-1,3-dipropylxanthine (DPCPX; 200 nM). When examined for individual experiments, cases with increases, or decreases, of facilitation following LTP were observed. These deviations showed no relation to initial release probability or to LTP magnitude, and they were also observed in control inputs not subjected to LTP. 4. Impairment of non-NMDA receptor desensitization by cyclothiazide (30 microM) increased facilitation observed during a 50 Hz, but not a 20 Hz, train. LTP had no effect on facilitation, in the presence of this drug, either during 20 or 50 Hz trains. 5. The results suggest that the effect of LTP in the hippocampal CA1 region on non-NMDA receptor-mediated synaptic responses to a brief afferent tetanus does not differ from that on a low-frequency, single volley-induced response. They do not support the notion that LTP is based on changes in release probability of previously active synapses. If LTP is based on recruitment of previously, pre- or postsynaptically, silent

  19. The E3 Ligase APC/C-Cdh1 Is Required for Associative Fear Memory and Long-Term Potentiation in the Amygdala of Adult Mice

    ERIC Educational Resources Information Center

    Pick, Joseph E.; Malumbres, Marcos; Klann, Eric

    2013-01-01

    The anaphase promoting complex/cyclosome (APC/C) is an E3 ligase regulated by Cdh1. Beyond its role in controlling cell cycle progression, APC/C-Cdh1 has been detected in neurons and plays a role in long-lasting synaptic plasticity and long-term memory. Herein, we further examined the role of Cdh1 in synaptic plasticity and memory by generating…

  20. Long term complications of diabetes

    MedlinePlus

    ... this page: //medlineplus.gov/ency/patientinstructions/000327.htm Long term complications of diabetes To use the sharing ... sores and infections. If it goes on too long, your toes, foot, or leg may need to ...

  1. Abdominal Pain, Long-Term

    MedlinePlus

    MENU Return to Web version Abdominal Pain, Long-term See complete list of charts. Ongoing or recurrent abdominal pain, also called chronic pain, may be difficult to diagnose, causing frustration for ...

  2. Long-term biomass research

    SciTech Connect

    Not Available

    1981-03-01

    Some of DOE's long term R and D programs for biomass are summarized in this article. These include research efforts in the fields of anaerobic digestion, energy farming, short rotation cultivation and aquatic farming. (DMC)

  3. Biodegradation potential of MTBE in a fractured chalk aquifer under aerobic conditions in long-term uncontaminated and contaminated aquifer microcosms.

    PubMed

    Shah, Nadeem W; Thornton, Steven F; Bottrell, Simon H; Spence, Michael J

    2009-01-26

    metabolites occurred. The availability of dissolved O2 did not affect MTBE biodegradation significantly, with similar MTBE biodegradation behaviour and rates down to ca. 0.7 mg/L dissolved O2 concentration. The results indicate that aerobic MTBE biodegradation could be significant in the plume fringe, during mixing of the contaminant plume and uncontaminated groundwater and that, relative to the plume migration, aerobic biodegradation is important for MTBE attenuation. Moreover, should the groundwater dissolved O2 concentration fall to zero such that MTBE biodegradation was inhibited, an engineered approach to enhance in situ bioremediation could supply O2 at relatively low levels (e.g. 2-3 mg/L) to effectively stimulate MTBE biodegradation, which has significant practical advantages. The study shows that aerobic MTBE biodegradation can occur at environmentally significant rates in this aquifer, and that long-term microcosm experiments (100s days) may be necessary to correctly interpret contaminant biodegradation potential in aquifers to support site management decisions.

  4. Long Term Surface Salinity Measurements

    NASA Technical Reports Server (NTRS)

    Schmitt, Raymond W.; Brown, Neil L.

    2005-01-01

    Our long-term goal is to establish a reliable system for monitoring surface salinity around the global ocean. Salinity is a strong indicator of the freshwater cycle and has a great influence on upper ocean stratification. Global salinity measurements have potential to improve climate forecasts if an observation system can be developed. This project is developing a new internal field conductivity cell that can be protected from biological fouling for two years. Combined with a temperature sensor, this foul-proof cell can be deployed widely on surface drifters. A reliable in-situ network of surface salinity sensors will be an important adjunct to the salinity sensing satellite AQUARIUS to be deployed by NASA in 2009. A new internal-field conductivity cell has been developed by N Brown, along with new electronics. This sensor system has been combined with a temperature sensor to make a conductivity - temperature (UT) sensor suitable for deployment on drifters. The basic sensor concepts have been proven on a high resolution CTD. A simpler (lower cost) circuit has been built for this application. A protection mechanism for the conductivity cell that includes antifouling protection has also been designed and built. Mr. A.Walsh of our commercial partner E-Paint has designed and delivered time-release formulations of antifoulants for our application. Mr. G. Williams of partner Clearwater Instrumentation advised on power and communication issues and supplied surface drifters for testing.

  5. Long-term equilibrium tides

    NASA Astrophysics Data System (ADS)

    Shaffer, John A.; Cerveny, Randall S.

    1998-08-01

    Extreme equilibrium tides, or ``hypertides,'' are computed in a new equilibrium tidal model combining algorithms of a version of the Chapront ELP-2000/82 Lunar Theory with the BER78 Milankovitch astronomical expansions. For the recent past, a high correspondence exists between computed semidiurnal tide levels and a record of coastal flooding demonstrating that astronomical alignment is a potential influence on such flooding. For the Holocene and near future, maximum tides demonstrate cyclic variations with peaks at near 5000 B.P. and 4000 A.P. On the late Quaternary timescale, variations in maximum equilibrium tide level display oscillations with periods of approximately 10,000, 100,000 and 400,000 years, because of precessional shifts in tidal maxima between vernal and autumnal equinoxes. While flooding occurs under the combined effects of tides and storms via ``storm surges,'' the most extensive flooding will occur with the coincidence of storms and the rarer hypertides and is thus primarily influenced by hypertides. Therefore we suggest that astronomical alignment's relationship to coastal flooding is probabilistic rather than deterministic. Data derived from this model are applicable to (1) archaeological and paleoclimatic coastal reconstructions, (2) long-term planning, for example, radioactive waste site selection, (3) sealevel change and paleoestuarine studies or (4) ocean-meteorological interactions.

  6. Rationale for a long-term evaluation of the consequences of potentially life-threatening maternal conditions and maternal "near-miss" incidents using a multidimensional approach.

    PubMed

    Pacagnella, Rodolfo C; Cecatti, Jose G; Camargo, Rodrigo P; Silveira, Carla; Zanardi, Dulce T; Souza, Joao P; Parpinelli, Mary A; Haddad, Samira M

    2010-08-01

    Recent advances in health care mean that women survive severe conditions and events related to pregnancy that would previously have resulted in death. Therefore, a greater number of women will experience significant maternal morbidity with significant consequences. Little is known, however, about these long-term consequences. Some investigators have evaluated the repercussions of severe biological or traumatic events, and have reported that survivors are at an increased risk of death in the five years after the event. In addition, they continue to experience both organic and emotional problems such as clinical, cardiac, respiratory, and neurological complications, as well as anxiety and depression, following discharge from hospital. Following a maternal "near-miss" incident, various life domains may be affected (organic, mental, cognitive, and social function), and these must be evaluated in addition to the related economic issues and quality of life. However, because of the diversity of methods and instruments used to evaluate possible repercussions, comparisons between the few studies available on the subject are difficult. An in-depth debate should be initiated to discuss the methodological aspects of such investigation. We propose a conceptual and methodological discussion on the long-term repercussions of severe maternal morbidity based on the evaluation of the following variables: reproductive health, quality of life, posttraumatic stress syndrome, sexual function, postpartum depression, daily functioning, and the physical, neurological, and psychomotor development of the children born after a complicated pregnancy.

  7. Potential for Local Fertilization: A Benthocosm Test of Long-Term and Short-Term Effects of Mussel Excretion on the Plankton

    PubMed Central

    Granados, Monica; Duffy, Sean; Robert, Pauline; Péquin, Bérangère; Mohit, Vani; McKindsey, Christopher W.; Archambault, Philippe; Myrand, Bruno; Lovejoy, Connie; Tremblay, Réjean; Plourde, Stéphane; Fussmann, Gregor F.

    2016-01-01

    Mussel aquaculture has expanded worldwide and it is important to assess its impact on the water column and the planktonic food web to determine the sustainability of farming practices. Mussel farming may affect the planktonic food web indirectly by excreting bioavailable nutrients in the water column (a short-term effect) or by increasing nutrient effluxes from biodeposit-enriched sediments (a long-term effect). We tested both of these indirect effects in a lagoon by using plankton-enclosing benthocosms that were placed on the bottom of a shallow lagoon either inside of a mussel farm or at reference sites with no history of aquaculture. At each site, half of the benthocosms were enriched with seawater that had held mussels (excretion treatment), the other half received non-enriched seawater as a control treatment. We monitored nutrients ([PO43-] and [NH4+]), dissolved oxygen and plankton components (bacteria, the phytoplankton and the zooplankton) over 5 days. We found a significant relationship between long-term accumulation of mussel biodeposits in sediments, water-column nutrient concentrations and plankton growth. Effects of mussel excretion were not detected, too weak to be significant given the spatial and temporal variability observed in the lagoon. Effects of mussels on the water column are thus likely to be coupled to benthic processes in such semi-enclosed water bodies. PMID:27249793

  8. Potential for Local Fertilization: A Benthocosm Test of Long-Term and Short-Term Effects of Mussel Excretion on the Plankton.

    PubMed

    Cherif, Mehdi; Granados, Monica; Duffy, Sean; Robert, Pauline; Péquin, Bérangère; Mohit, Vani; McKindsey, Christopher W; Archambault, Philippe; Myrand, Bruno; Lovejoy, Connie; Tremblay, Réjean; Plourde, Stéphane; Fussmann, Gregor F

    2016-01-01

    Mussel aquaculture has expanded worldwide and it is important to assess its impact on the water column and the planktonic food web to determine the sustainability of farming practices. Mussel farming may affect the planktonic food web indirectly by excreting bioavailable nutrients in the water column (a short-term effect) or by increasing nutrient effluxes from biodeposit-enriched sediments (a long-term effect). We tested both of these indirect effects in a lagoon by using plankton-enclosing benthocosms that were placed on the bottom of a shallow lagoon either inside of a mussel farm or at reference sites with no history of aquaculture. At each site, half of the benthocosms were enriched with seawater that had held mussels (excretion treatment), the other half received non-enriched seawater as a control treatment. We monitored nutrients ([PO43-] and [NH4+]), dissolved oxygen and plankton components (bacteria, the phytoplankton and the zooplankton) over 5 days. We found a significant relationship between long-term accumulation of mussel biodeposits in sediments, water-column nutrient concentrations and plankton growth. Effects of mussel excretion were not detected, too weak to be significant given the spatial and temporal variability observed in the lagoon. Effects of mussels on the water column are thus likely to be coupled to benthic processes in such semi-enclosed water bodies. PMID:27249793

  9. Muscle derived stem cell contains the potential to enhance long term retention as well as an aesthetic outcome of autologous fat grafting.

    PubMed

    Han, Duanyang; Ma, Zhiqiang; Zhang, Peipei; Yang, Jenny F; Zhang, Yingbo; Yang, Daping; Liu, Jianyu

    2011-06-01

    Autologous fat graft has been mentioned as a prospective source of soft-tissue filler for decades. It gives a natural consistency, is easy and safe to harvest, exhibits no hypersensitivity or foreign body reactions, and is readily available. However, the traditional fat grafting has its limitations in long term process, such as partial necrosis, loss of volume, and internal calcification. They all compromise the functional and aesthetic outcome of this procedure. In recent studies, the best results were obtained by transplanting fat tissue inside muscle, thus benefiting from its better blood supply. Muscle-derived stem cells have recently emerged as a promising source of multipotent cells which give rise to muscle fibers within muscular environment. Previous studies have also proved that muscle-derived stem cells are capable of releasing various kinds of angiogenesis agents, such as VEGF, HGF, and FGF. These cytokines are known to promote revascularization. Based on the foregoing facts, we postulate that co-transplant of autologous fat and muscle derived stem cells may enhance the long term retention and aesthetic outcome of fat grafting. PMID:21419577

  10. Epinephrine: a short- and long-term regulator of stress and development of illness : a potential new role for epinephrine in stress.

    PubMed

    Wong, Dona Lee; Tai, T C; Wong-Faull, David C; Claycomb, Robert; Meloni, Edward G; Myers, Karyn M; Carlezon, William A; Kvetnansky, Richard

    2012-07-01

    Epinephrine (Epi), which initiates short-term responses to cope with stress, is, in part, stress-regulated via genetic control of its biosynthetic enzyme, phenylethanolamine N-methyltransferase (PNMT). In rats, immobilization (IMMO) stress activates the PNMT gene in the adrenal medulla via Egr-1 and Sp1 induction. Yet, elevated Epi induced by acute and chronic stress is associated with stress induced, chronic illnesses of cardiovascular, immune, cancerous, and behavioral etiologies. Major sources of Epi include the adrenal medulla and brainstem. Although catecholamines do not cross the blood-brain barrier, circulating Epi from the adrenal medulla may communicate with the central nervous system and stress circuitry by activating vagal nerve β-adrenergic receptors to release norepinephrine, which could then stimulate release of the same from the nucleus tractus solitarius and locus coeruleus. In turn, the basal lateral amygdala (BLA) may activate to stimulate afferents to the hypothalamus, neocortex, hippocampus, caudate nucleus, and other brain regions sequentially. Recently, we have shown that repeated IMMO or force swim stress may evoke stress resiliency, as suggested by changes in expression and extinction of fear memory in the fear-potentiated startle paradigm. However, concomitant adrenergic changes seem stressor dependent. Present studies aim to identify stressful conditions that elicit stress resiliency versus stress sensitivity, with the goal of developing a model to investigate the potential role of Epi in stress-associated illness. If chronic Epi over expression does elicit illness, possibilities for alternative therapeutics exist through regulating stress-induced Epi expression, adrenergic receptor function and/or corticosteroid effects on Epi, adrenergic receptors and the stress axis.

  11. Potential long-term effects of a mind-body intervention for women with major depressive disorder: sustained mental health improvements with a pilot yoga intervention.

    PubMed

    Kinser, Patricia Anne; Elswick, R K; Kornstein, Susan

    2014-12-01

    Despite pharmacologic and psychotherapeutic advances over the past decades, many individuals with major depressive disorder (MDD) experience recurrent depressive episodes and persistent depressive symptoms despite treatment with the usual care. Yoga is a mind-body therapeutic modality that has received attention in both the lay and research literature as a possible adjunctive therapy for depression. Although promising, recent findings about the positive mental health effects of yoga are limited because few studies have used standardized outcome measures and none of them have involved long-term follow-up beyond a few months after the intervention period. The goal of our research study was to evaluate the feasibility, acceptability, and effects of a yoga intervention for women with MDD using standardized outcome measures and a long follow-up period (1year after the intervention). The key finding is that previous yoga practice has long-term positive effects, as revealed in both qualitative reports of participants' experiences and in the quantitative data about depression and rumination scores over time. Although generalizability of the study findings is limited because of a very small sample size at the 1-year follow-up assessment, the trends in the data suggest that exposure to yoga may convey a sustained positive effect on depression, ruminations, stress, anxiety, and health-related quality of life. Whether an individual continues with yoga practice, simple exposure to a yoga intervention appears to provide sustained benefits to the individual. This is important because it is rare that any intervention, pharmacologic or non-pharmacologic, for depression conveys such sustained effects for individuals with MDD, particularly after the treatment is discontinued.

  12. Potential long-term effects of a mind-body intervention for women with major depressive disorder: sustained mental health improvements with a pilot yoga intervention.

    PubMed

    Kinser, Patricia Anne; Elswick, R K; Kornstein, Susan

    2014-12-01

    Despite pharmacologic and psychotherapeutic advances over the past decades, many individuals with major depressive disorder (MDD) experience recurrent depressive episodes and persistent depressive symptoms despite treatment with the usual care. Yoga is a mind-body therapeutic modality that has received attention in both the lay and research literature as a possible adjunctive therapy for depression. Although promising, recent findings about the positive mental health effects of yoga are limited because few studies have used standardized outcome measures and none of them have involved long-term follow-up beyond a few months after the intervention period. The goal of our research study was to evaluate the feasibility, acceptability, and effects of a yoga intervention for women with MDD using standardized outcome measures and a long follow-up period (1year after the intervention). The key finding is that previous yoga practice has long-term positive effects, as revealed in both qualitative reports of participants' experiences and in the quantitative data about depression and rumination scores over time. Although generalizability of the study findings is limited because of a very small sample size at the 1-year follow-up assessment, the trends in the data suggest that exposure to yoga may convey a sustained positive effect on depression, ruminations, stress, anxiety, and health-related quality of life. Whether an individual continues with yoga practice, simple exposure to a yoga intervention appears to provide sustained benefits to the individual. This is important because it is rare that any intervention, pharmacologic or non-pharmacologic, for depression conveys such sustained effects for individuals with MDD, particularly after the treatment is discontinued. PMID:25457687

  13. Long-term parenteral nutrition

    PubMed Central

    Ladefoged, Karin; Jarnum, Stig

    1978-01-01

    Nineteen patients (11 women and eight men) aged 20-68 received long-term parenteral nutrition, mostly at home, for six to 63 months (mean 19 months). Indications for LTPN were extensive, active Crohn's disease in three patients, intestinocutaneous fistulas in three, and short-bowel syndrome in the remaining 13 patients. Subclavian or intra-atrial (Broviac) catheters were most commonly used, for which the average life was four and seven months respectively. Complications of long-term parenteral nutrition included pneumothorax in four out of 48 subclavian vein punctures. Catheter-induced thrombosis of central veins was shown by phlebography 17 times in nine patients, and eight episodes of total occlusion occurred. Two of these patients had pulmonary infarction. Nineteen episodes of catheter sepsis occurred in 11 patients, but only one was fatal. Complications related to intestinal disease included intra-abdominal abscesses and intestinal fistulas, and disturbances of liver function. Five patients died, though in only two was death related to long-term parenteral nutrition. One of these patients died from catheter sepsis, the other had subdural haematoma possibly caused by anticoagulant treatment. Eight of the 14 surviving patients still needed parenteral nutrition. All received a disability pension, but six had an acceptable quality of life with almost normal social activities. Despite problems such as difficulties in maintaining standardised infusion programmes, it was concluded that long-term parenteral nutrition at home is practicable and consistent with an acceptable quality of life. ImagesFIG 2 PMID:98199

  14. A long-term investigation of the anti-hepatocarcinogenic potential of an indigenous medicine comprised of Nigella sativa, Hemidesmus indicus and Smilax glabra

    PubMed Central

    Iddamaldeniya, SS; Thabrew, MI; Wickramasinghe, SMDN; Ratnatunge, N; Thammitiyagodage, MG

    2006-01-01

    Background A decoction comprised of Nigella sativa seeds, Hemidesmus indicus root bark and Smilax glabra rhizome is being recommended for cancer patients by a family of traditional medical practitioners of Sri Lanka. Previous investigations have demonstrated that a short term (10 weeks) treatment with the decoction can significantly inhibit diethylnitrosamine (DEN) mediated expression of Glutathione S-transferase P form (GST-P) in rat liver. The objective of the present investigation was to determine whether long term (16 months) treatment with the decoction would be successful in inhibiting in rat livers, not only DEN- mediated expression of GST-P, but also the carcinogen mediated development of overt tumours (OT) or histopathological changes leading to tumour development (HT). Methods Thirty-six male Wistar rats were divided into 3 groups of 12 each. Groups 1 and 2 were injected intraperitoneally (i.p) with DEN (200 mg/kg) while group 3 was injected normal saline (NS). Twenty-four hours later, decoction (DC; 6 g/kg body weight/day) was orally administered to group 1 rats, while groups 2 and 3 (DEN-control and normal control) were given distilled water (DW). Treatment with DC or DW continued for 16 months. At the end of the 9th month and 16th months (study 1 and study 2 respectively), six rats from each group were sacrificed, and livers observed for OT or HT, both visually and by subjecting liver sections to staining with Haemotoxylin and Eosin (H & E), Sweet's Silver stain (for reticulin fibers), Periodic Acid Schiff (PAS) staining (for glycogen), and immunohistochemical staining (for GST-P). Results At the end of 9 months (study 1) a hepatocellular adenoma (HA) developed in one of the rats in the DEN + DW treated group (group 2). At the end of 16 months (study 2), livers of all rats of group 2 developed OT and HT. Large areas of GST-P positive foci were also observed. No OT, HT or GST-P positive foci were detected in any of the other groups. Conclusion

  15. Long-term data archiving

    SciTech Connect

    Moore, David Steven

    2009-01-01

    Long term data archiving has much value for chemists, not only to retain access to research and product development records, but also to enable new developments and new discoveries. There are some recent regulatory requirements (e.g., FDA 21 CFR Part 11), but good science and good business both benefit regardless. A particular example of the benefits of and need for long term data archiving is the management of data from spectroscopic laboratory instruments. The sheer amount of spectroscopic data is increasing at a scary rate, and the pressures to archive come from the expense to create the data (or recreate it if it is lost) as well as its high information content. The goal of long-term data archiving is to save and organize instrument data files as well as any needed meta data (such as sample ID, LIMS information, operator, date, time, instrument conditions, sample type, excitation details, environmental parameters, etc.). This editorial explores the issues involved in long-term data archiving using the example of Raman spectral databases. There are at present several such databases, including common data format libraries and proprietary libraries. However, such databases and libraries should ultimately satisfy stringent criteria for long term data archiving, including readability for long times into the future, robustness to changes in computer hardware and operating systems, and use of public domain data formats. The latter criterion implies the data format should be platform independent and the tools to create the data format should be easily and publicly obtainable or developable. Several examples of attempts at spectral libraries exist, such as the ASTM ANDI format, and the JCAMP-DX format. On the other hand, proprietary library spectra can be exchanged and manipulated using proprietary tools. As the above examples have deficiencies according to the three long term data archiving criteria, Extensible Markup Language (XML; a product of the World Wide Web

  16. Recent advances in long-term climate and moisture reconstructions from the Baltic region: Exploring the potential for a new multi-millennial tree-ring chronology

    NASA Astrophysics Data System (ADS)

    Edvardsson, Johannes; Corona, Christophe; Mažeika, Jonas; Pukienė, Rutile; Stoffel, Markus

    2016-01-01

    This study presents the first results from an ongoing initiative to develop a multi-millennial Baltic tree-ring width (TRW) chronology consisting of 12 floating records from subfossil Scots pines (Pinus sylvestris L.) extracted from three Lithuanian peat-mining areas. The floating series have been complemented with absolutely dated TRW chronologies which were obtained from living trees growing in unmanaged and unexploited peatland areas adjacent to each of the above study sites. The subfossil material has been dated by radiocarbon and shows a temporal spread over the last 6000 years, with assemblages of trees during the Holocene Thermal Maximum (HTM; 8000-4000 BP) and the onset of the Medieval Warm Period (MWP, AD 900-1350). Annual tree growth and sample replication of peatland pines reflect moisture variations and long-term climate variability. The importance of extending the TRW chronologies should not therefore be underestimated as (1) climate records of comparable length and resolution do not exist for the Baltic region, but also as (2) a result of a widespread lack of detailed moisture proxies spanning several millennia. Our data clearly show that a 6000-yr, continuous pine chronology from the Baltic region is a realistic objective, and would doubtlessly fill a major geographic gap in an ecologically sensitive region located at the interface between the temperate and boreal vegetation zones.

  17. Evidence that limbic neural plasticity in the right hemisphere mediates partial kindling induced lasting increases in anxiety-like behavior: effects of low frequency stimulation (quenching?) on long term potentiation of amygdala efferents and behavior following kindling.

    PubMed

    Adamec, R E

    1999-08-21

    Behavioral and physiological effects of partial kindling of the right ventral hippocampus by perforant path (PP) stimulation were investigated in the cat. Partial kindling produced lasting changes in affect (increased defensive response to rats) and predatory attack (decreased pawing and biting attack). Partial kindling also induced long term potentiation (LTP) of amygdala efferent transmission to ventromedial hypothalamus (VMH) and periaqueductal gray (PAG) in left and right hemispheres. LTP of field population spikes evoked in area CA3 by PP stimulation was also observed. LTP was detected using evoked potential methods. These findings parallel previous studies of left PP-CA3 partial kindling. Analysis of covariance removing effects of LTP from behavioral changes suggests that initiation of increased defensiveness at 2 days after completion of partial kindling depended on LTP of left and right amygdalo-VMH and right amygdalo-PAG transmission. From 6 days after kindling onward, increased defensiveness depended on LTP of right amygdalo-PAG transmission. Depotentiation of amygdala efferent LTP by bilateral low frequency amygdala stimulation (LFS) (900 pulses at 1 Hz, once daily for 7 days) selectively reduced LTP in right amygdala efferents. At the same time, defensive, but not predatory attack behavior, was returned to levels seen prior to partial kindling. Both depotentiation and reduction of defensiveness were transient. Defensiveness increased to post-kindling levels by 76 days after LFS. At the same time, LTP was restored in the right amygdalo-PAG pathway. In contrast LTP in the right amygdalo-VMH pathway remained depotentiated. Effects of LFS were not due to damage, as thresholds to evoke amygdala efferent response were unchanged. These findings suggest that lasting change in affect following partial hippocampal kindling depends on LTP of right amygdala efferent transmission to PAG. The findings parallel studies of non-convulsant pharmacological induction of

  18. Dopamine receptors and groups I and II mGluRs cooperate for long-term depression induction in rat prefrontal cortex through converging postsynaptic activation of MAP kinases.

    PubMed

    Otani, S; Auclair, N; Desce, J M; Roisin, M P; Crépel, F

    1999-11-15

    Tetanic stimuli to layer I-II afferents in rat prefrontal cortex induced long-term depression (LTD) of layer I-II to layer V pyramidal neuron glutamatergic synapses when tetani were coupled to bath application of dopamine. This LTD was blocked by the following metabotropic glutamate receptor (mGluR) antagonists coapplied with dopamine: (S)-alpha-methyl-4-carboxyphenylglycine (MCPG; group I and II antagonist), (RS)-1-aminoindan-1,5-dicarboxylic acid (AIDA; group I antagonist), or (RS)-alpha-methylserine-O-phosphate monophenyl ester (MSOPPE; group II antagonist). This suggests that the dopamine-facilitated LTD requires synaptic activation of groups I and II mGluRs during tetanus. LTD could also be induced by coupling tetani to bath application of groups I and II mGluR agonist (1S, 3R)-1-aminocyclopentane-1,3-dicarboxylic acid (1S,3R-ACPD). In the next series of experiments, coapplication of dopamine and 1S,3R-ACPD, but not application of either drug alone, consistently induced LTD without tetani or even single test stimuli during drug application, suggesting that coactivation of dopamine receptors and the mGluRs is sufficient for LTD induction. Immunoblot analyses with anti-active mitogen-activated protein kinases (MAP-Ks) revealed that D1 receptors, D2 receptors, group I mGluRs, and group II mGluRs all contribute to MAP-K activation in prefrontal cortex, and that combined activation of dopamine receptors and mGluRs synergistically or additively activate MAP-Ks. Consistently, LTD by dopamine + 1S, 3R-ACPD coapplication, as well as the two other forms of LTD (LTD by dopamine + tetani and LTD by 1S,3R-ACPD + tetani), was blocked by bath application of MAP-K kinase inhibitor PD98059. LTD by dopamine + 1S,3R-ACPD coapplication was also blocked by postsynaptic injection of synthetic MAP-K substrate peptide. Our results suggest that dopamine receptors and groups I and II mGluRs cooperate to induce LTD through converging postsynaptic activation of MAP-Ks.

  19. Evaluation of guanfacine as a potential medication for alcohol use disorder in long-term drinking rats: behavioral and electrophysiological findings.

    PubMed

    Fredriksson, Ida; Jayaram-Lindström, Nitya; Wirf, Malin; Nylander, Erik; Nyström, Erica; Jardemark, Kent; Steensland, Pia

    2015-03-13

    One of the main treatment challenges in alcohol use disorder (AUD) is the high rate of craving in combination with decreased cognitive functioning including impaired decision making and impulse control that often lead to relapse. Recent studies show that guanfacine, an α-2-adrenoceptor agonist and FDA-approved ADHD medication, attenuates stress-induced relapse of several drugs of abuse including alcohol. Here we evaluated guanfacine's effects on voluntary alcohol intake, the alcohol deprivation effect (ADE), alcohol seeking behavior, and cue/priming-induced reinstatement in Wistar rats that had voluntarily consumed alcohol for at least 2 months before treatment. In addition, guanfacine's ability to regulate glutamatergic neurotransmission was evaluated through electrophysiological recordings in medial prefrontal cortex (mPFC) slices prepared from long-term drinking rats (and alcohol-naive controls) that had received three daily guanfacine (0.6 mg/kg/day) or vehicle injections in vivo. Guanfacine decreased alcohol intake in high, but not low, alcohol-consuming rats and the effects were generally more long lasting than that of the AUD medication naltrexone. Repeated guanfacine treatment induced a long-lasting decrease in alcohol intake, persistent up to five drinking sessions after the last injection. In addition, guanfacine attenuated the ADE as well as alcohol seeking and cue/priming-induced reinstatement of alcohol seeking. Finally, subchronic guanfacine treatment normalized an alcohol-induced dysregulated glutamatergic neurotransmission in the mPFC. These results support previous studies showing that guanfacine has the ability to improve prefrontal connectivity through modulation of the glutamatergic system. Together with the fact that guanfacine appears to be clinically safe, these results merit evaluation of guanfacine's clinical efficacy in AUD individuals.

  20. Leukodepleted blood components do not remove the potential for long-term transfusion-associated microchimerism in Australian major trauma patients

    PubMed Central

    Hirani, Rena; Balogh, Zsolt J; Lott, Natalie J; Hsu, Jeremy M; Irving, David O

    2014-01-01

    Despite the introduction of leukodepleted blood components, it has been shown that donor leukocyte engraftment (microchimerism) remains a long-term consequence of red blood cell (RBC) transfusion. The incidence of microchimerism may be affected by international disparities in blood processing methods or variations in transfusion practices. This study was conducted to determine the prevalence of microchimerism in Australian trauma patients. A secondary aim was to examine whether any patient complications correlated to the incidence of microchimerism. Australian trauma patients (n = 86) who had been transfused with red blood cell (RBC) units between 2000 and 2012 with an injury severity score (ISS) of greater than 15 were recruited. The prevalence of microchimerism was determined using genetic screening with a panel of insertion/deletion biallelic polymorphisms. The mean storage age of the transfused RBC units was 20 ± 8 days and the mean length of stay (LOS) in hospital was 40 ± 39 days. There were no significant associations in this study sample to bias for patient age, gender, number of transfused RBC units or ISS. Nine of the 55 (16.3%) patients transfused with non-leukodepleted blood components displayed an incidence of microchimerism. Of the 31 patients transfused with leukodepleted RBC units, 3 (9.6%) displayed an incidence of microchimerism. Therefore, despite the universal introduction of leukodepleted blood components in Australia, the prevalence of transfusion-associated microchimerism was found to be unchanged. Furthermore, half of the patients exhibiting microchimerism were recorded to have had splenic injury or required splenectomy at the time of transfusion. PMID:26252809

  1. Electrodes for long-term esophageal electrocardiography.

    PubMed

    Niederhauser, Thomas; Haeberlin, Andreas; Marisa, Thanks; Jungo, Michael; Goette, Josef; Jacomet, Marcel; Abacherli, Roger; Vogel, Rolf

    2013-09-01

    The emerging application of long-term and high-quality ECG recording requires alternative electrodes to improve the signal quality and recording capability of surface skin electrodes. The esophageal ECG has the potential to overcome these limitations but necessitates novel recorder and lead designs. The electrode material is of particular interest, since the material has to ensure conflicting requirements like excellent biopotential recording properties and inertness. To this end, novel electrode materials like PEDOT and silver-PDMS as well as established electrode materials such as stainless steel, platinum, gold, iridium oxide, titanium nitride, and glassy carbon were investigated by long-term electrochemical impedance spectroscopy and model-based signal analysis using the derived in vitro interfacial properties in conjunction with a dedicated ECG amplifier. The results of this novel approach show that titanium nitride and iridium oxide featuring microstructured surfaces did not degrade when exposed to artificial acidic saliva. These materials provide low electrode potential drifts and insignificant signal distortion superior to surface skin electrodes making them compatible with accepted standards for ambulatory ECG. They are superior to the noble and polarizable metals such as platinum, silver, and gold that induced more signal distortions and are superior to esophageal stainless steel electrodes that corrode in artificial saliva. The study provides rigorous criteria for the selection of electrode materials for prolonged ECG recording by combining long-term in vitro electrode material properties with ECG signal quality assessment.

  2. IMPAIRMENT IN SHORT-TERM BUT ENHANCED LONG-TERM SYNAPTIC POTENTIATION AND ERK ACTIVATION IN ADULT HIPPOCAMPAL AREA CA1 FOLLOWING DEVELOPMENTAL HYPOTHYROIDISM.

    EPA Science Inventory

    The EPA must evaluate the risk of exposure of the developing brain to chemicals with the potential to disrupt thyroid hormone homeostasis. The existing literature identifies morphological and neurochemical indices of severe neonatal hypothyroidism in the early postnatal period i...

  3. Potential long-term chemical effects of diesel fuel emissions on a mining environment: A preliminary assessment based on data from a deep subsurface tunnel at Rainer Mesa, Nevada test site

    SciTech Connect

    Meike, A.; Bourcier, W.L.; Alai, M.

    1995-09-01

    The general purpose of the Yucca Mountain Site Characterization Project (YMSCP) Introduced Materials Task is to understand and predict potential long-term modifications of natural water chemistry related to the construction and operation of a radioactive waste repository that may significantly affect performance of the waste packages. The present study focuses on diesel exhaust. Although chemical information on diesel exhaust exists in the literature, it is either not explicit or incomplete, and none of it establishes mechanisms that might be used to predict long-term behavior. In addition, the data regarding microbially mediated chemical reactions are not well correlated with the abiotic chemical data. To obtain some of the required long-term information, we chose a historical analog: the U12n tunnel at Rainier Mesa, Nevada Test Site. This choice was based on the tunnel`s extended (30-year) history of diesel usage, its geological similarity to Yucca Mountain, and its availability. The sample site within the tunnel was chosen based on visual inspection and on information gathered from miners who were present during tunnel operations. The thick layer of dark deposit at that site was assumed to consist primarily of rock powder and diesel exhaust. Surface samples and core samples were collected with an intent to analyze the deposit and to measure potential migration of chemical components into the rock. X-ray diffraction (XRD), x-ray fluorescence (XRF), scanning electron microscopy (SEM) with energy dispersive spectra (EDS) analysis, secondary-ion mass spectrometry (SIMS), and Fourier transform infrared (FTIR) analysis were used to measure both spatial distribution and concentration for the wide variety of chemical components that were expected based on our literature survey.

  4. Long-Term Corrosion Potential Behavior of Alloy 22 in Hot 5 m CaCl2 + 5 m Ca(NO3)2 Brines

    SciTech Connect

    Rodriguez, M A; Carranza, R M; Stuart, M L; Rebak, R B

    2007-02-20

    Alloy 22 is a nickel base alloy highly resistant to all forms of corrosion. In very aggressive conditions (e.g. hot concentrated chloride containing brines) Alloy 22 could suffer localized attack, namely pitting and crevice corrosion. The occurrence of localized corrosion in a given environment is governed by the values of the critical potential (E{sub crit}) for crevice corrosion and the corrosion potential (E{sub corr}) that the alloy may establish in the studied environment. If E{sub corr} is equal or higher than E{sub crit}, localized corrosion may be expected. This paper discusses the evolution of E{sub corr} of Alloy 22 specimens in 5 m CaCl{sub 2} + 5 m Ca(NO{sub 3}){sub 2} brines at 100 C and 120 C. Two types of specimens were used, polished as-welded (ASW) creviced and noncreviced specimens and as-welded plus solution heat-treated (ASW+SHT) creviced specimens. The latter contained the black annealing oxide film on the surface. Results show that, for all types of Alloy 22 specimens the E{sub corr} was higher at 120 C than at 100 C, probably because a more protective film formed at the higher temperature. Specimens with the black oxide film on the surface showed more oscillations in the potential. None of the tested specimens suffered crevice corrosion probably because of the relatively high concentration of nitrate in the electrolyte, R = [NO3]/[Cl] = 1.

  5. Polyaromatic hydrocarbon (PAH) degradation potential of a new acid tolerant, diazotrophic P-solubilizing and heavy metal resistant bacterium Cupriavidus sp. MTS-7 isolated from long-term mixed contaminated soil.

    PubMed

    Kuppusamy, Saranya; Thavamani, Palanisami; Megharaj, Mallavarapu; Lee, Yong Bok; Naidu, Ravi

    2016-11-01

    An isolate of Cupriavidus (strain MTS-7) was identified from a long-term PAHs and heavy metals mixed contaminated soil with the potential to biodegrade both LMW and HMW PAHs with added unique traits of acid and alkali tolerance, heavy metal tolerance, self-nutrient assimilation by N fixation and P solubilization. This strain completely degraded the model 3 (150 mg L(-1) Phe), 4 (150 mg L(-1) Pyr) and 5 (50 mg L(-1) BaP) ring PAHs in 4, 20 and 30 days, respectively. It could mineralize 90-100% of PAHs (200 mg L(-1) of Phe and Pyr) within 15 days across pH ranging from 5 to 8 and even in the presence of toxic metal contaminations. During biodegradation, the minimum inhibitory concentrations were 5 (Cu(2+)) and 3 (Cd(2+), Pb(2+), Zn(2+)) mg L(-1) of the potentially bioavailable metal ions and over 17 mg L(-1) metal levels was lethal for the microbe. Further, it could fix 217-274 μg mL(-1) of N and solubilize 79-135 μg mL(-1) of P while PAHs degradation. MTS-7 as a superior candidate could be thus used in the enhanced bioaugmentation and/or phytoremediation of long-term mixed contaminated sites. PMID:27475295

  6. Mice lacking the PSD-95–interacting E3 ligase, Dorfin/Rnf19a, display reduced adult neurogenesis, enhanced long-term potentiation, and impaired contextual fear conditioning

    PubMed Central

    Park, Hanwool; Yang, Jinhee; Kim, Ryunhee; Li, Yan; Lee, Yeunkum; Lee, Chungwoo; Park, Jongil; Lee, Dongmin; Kim, Hyun; Kim, Eunjoon

    2015-01-01

    Protein ubiquitination has a significant influence on diverse aspects of neuronal development and function. Dorfin, also known as Rnf19a, is a RING finger E3 ubiquitin ligase implicated in amyotrophic lateral sclerosis and Parkinson’s disease, but its in vivo functions have not been explored. We report here that Dorfin is a novel binding partner of the excitatory postsynaptic scaffolding protein PSD-95. Dorfin-mutant (Dorfin−/−) mice show reduced adult neurogenesis and enhanced long-term potentiation in the hippocampal dentate gyrus, but normal long-term potentiation in the CA1 region. Behaviorally, Dorfin−/− mice show impaired contextual fear conditioning, but normal levels of cued fear conditioning, fear extinction, spatial learning and memory, object recognition memory, spatial working memory, and pattern separation. Using a proteomic approach, we also identify a number of proteins whose ubiquitination levels are decreased in the Dorfin−/− brain. These results suggest that Dorfin may regulate adult neurogenesis, synaptic plasticity, and contextual fear memory. PMID:26553645

  7. Transplantation-Associated Long-Term Immunosuppression Promotes Oral Colonization by Potentially Opportunistic Pathogens without Impacting Other Members of the Salivary Bacteriome

    PubMed Central

    Hong, Bo-Young; Frias-Lopez, Jorge; Dupuy, Amanda K.; Angeloni, Mark; Abusleme, Loreto; Terzi, Evimaria; Ioannidou, Effie; Strausbaugh, Linda D.

    2013-01-01

    Solid-organ transplant recipients rely on pharmacological immunosuppression to prevent allograft rejection. The effect of such chronic immunosuppression on the microflora at mucosal surfaces is not known. We evaluated the salivary bacterial microbiome of 20 transplant recipients and 19 nonimmunosuppressed controls via 454 pyrosequencing of 16S rRNA gene amplicons. Alpha-diversity and global community structure did not differ between transplant and control subjects. However, principal coordinate analysis showed differences in community membership. Taxa more prevalent in transplant subjects included operational taxonomic units (OTUs) of potentially opportunistic Gammaproteobacteria such as Klebsiella pneumoniae, Pseudomonas fluorescens, Acinetobacter species, Vibrio species, Enterobacteriaceae species, and the genera Acinetobacter and Klebsiella. Transplant subjects also had increased proportions of Pseudomonas aeruginosa, Acinetobacter species, Enterobacteriaceae species, and Enterococcus faecalis, among other OTUs, while genera with increased proportions included Klebsiella, Acinetobacter, Staphylococcus, and Enterococcus. Furthermore, in transplant subjects, the dose of the immunosuppressant prednisone positively correlated with bacterial richness, while prednisone and mycophenolate mofetil doses positively correlated with the prevalence and proportions of transplant-associated taxa. Correlation network analysis of OTU relative abundance revealed a cluster containing potentially opportunistic pathogens as transplant associated. This cluster positively correlated with serum levels of C-reactive protein, suggesting a link between the resident flora at mucosal compartments and systemic inflammation. Network connectivity analysis revealed opportunistic pathogens as highly connected to each other and to common oral commensals, pointing to bacterial interactions that may influence colonization. This work demonstrates that immunosuppression aimed at limiting T

  8. Long Term Analysis for the BAM device

    NASA Astrophysics Data System (ADS)

    Bonino, D.; Gardiol, D.

    2011-02-01

    Algorithms aimed at the evaluation of critical quantities are based on models with many parameters, which values are estimated from data. The knowledge, with high accuracy, of these values and the control of their temporal evolution are important features. In this work, we focus on the latter subject, and we show a proposed pipeline for the BAM (Basic Angle Monitoring) Long Term Analysis, aimed at the study of the calibration parameters of the BAM device and of the Basic Angle variation, searching for unwanted trends, cyclic features, or other potential unexpected behaviours.

  9. TiO2 nanotube arrays deposited on Ti substrate by anodic oxidation and their potential as a long-term drug delivery system for antimicrobial agents

    NASA Astrophysics Data System (ADS)

    Moseke, Claus; Hage, Felix; Vorndran, Elke; Gbureck, Uwe

    2012-05-01

    Nanotube arrays on medical titanium surfaces were fabricated by two different anodization methods and their potential for storage and release of antimicrobial substances was evaluated. The treatment of the Ti surfaces in fluoride containing electrolytes on water as well as on polyethylene glycol basis led to the formation of TiO2 nanotubes with up to 6.54 μm length and average diameters of up to 160 nm. Drug release experiments with the model antibiotic vancomycin and with antibacterial silver ions showed that the increased surface area of the anodized samples enabled them to be loaded with up to 450% more active agent than the untreated Ti surfaces. Significant surface-dependent differences in the release kinetics of vancomycin were observed. In comparison to surfaces anodized in an aqueous electrolyte, the release of the antibiotic from surfaces anodized in an electrolyte based on ethylene glycol was significantly retarded, with a release of noticeable amounts over a period of more than 300 days. Loading of nanotube surfaces fabricated in aqueous electrolyte with silver ions revealed increased amounts of adsorbed silver by up to 230%, while the release kinetics showed significant differences in comparison to untreated Ti. It was concluded that nanotube arrays on favored medical implant materials have a high potential for loading with antimicrobial agents and also provide the possibility of tailored release kinetics by variation of anodization parameters.

  10. Long-term oral administration of memory-enhancing doses of tacrine in mice: a study of potential toxicity and side effects.

    PubMed

    Fitten, L J; Flood, J F; Baxter, C F; Tachiki, K H; Perryman, K

    1987-11-01

    Recently, tacrine (1, 2, 3, 4-tetrahydro-9-aminoacridine; THA; TAC) has received international attention as an oral agent capable of relieving some of the cognitive symptoms accompanying Alzheimer's disease (AD). When given acutely and parenterally (by injection), tacrine has also enhanced memory retention in animals and man. This study evaluates the clinical potential of this agent by assessing toxicity and major side effects of a memory-enhancing dose of tacrine in mice. Groups of mice received either tacrine or vehicle (placebo) orally for 4 to 6 months. A lack of toxicity after this prolonged treatment with TAC was indicated by: (a) no significant impairment on a battery of behavioral toxicity tests; (b) improved memory retention; (c) a significant but only slight elevation of ornithine transcarbamylase activity in blood serum; (d) no abnormality as revealed with light microscopy of liver tissue; and (e) no gross organ pathology in visceral organs.

  11. Long-term agricultural land-cover change and potential for cropland expansion in the former Virgin Lands area of Kazakhstan

    NASA Astrophysics Data System (ADS)

    Kraemer, Roland; Prishchepov, Alexander V.; Müller, Daniel; Kuemmerle, Tobias; Radeloff, Volker C.; Dara, Andrey; Terekhov, Alexey; Frühauf, Manfred

    2015-05-01

    During the Soviet Virgin Lands Campaign, approximately 23 million hectares (Mha) of Eurasian steppe grassland were converted into cropland in Northern Kazakhstan from 1954 to 1963. As a result Kazakhstan became an important breadbasket of the former Soviet Union. However, the collapse of the Soviet Union in 1991 triggered widespread agricultural abandonment, and much cropland reverted to grasslands. Our goal in this study was to reconstruct and analyze agricultural land-cover change since the eve of the Virgin Lands Campaign, from 1953 to 2010 in Kostanay Province, a region that is representative of Northern Kazakhstan. Further, we assessed the potential of currently idle cropland for re-cultivation. We reconstructed the cropland extent before and after the Virgin Lands Campaign using archival maps, and we mapped the agricultural land cover in the late Soviet and post-Soviet period using multi-seasonal Landsat TM/ETM+ images from circa 1990, 2000 and 2010. Cropland extent peaked at approximately 3.1 Mha in our study area in 1990, 38% of which had been converted from grasslands from 1954 to 1961. After the collapse of the Soviet Union, 45% of the Soviet cropland was abandoned and had reverted to grassland by 2000. After 2000, cropland contraction and re-cultivation were balanced. Using spatial logistic regressions we found that cropland expansion during the Virgin Lands Campaign was significantly associated with favorable agro-environmental conditions. In contrast, cropland expansion after the Campaign until 1990, as well as cropland contraction after 1990, occurred mainly in areas that were less favorable for agriculture. Cropland re-cultivation after 2000 was occurring on lands with relatively favorable agro-environmental conditions in comparison to remaining idle croplands, albeit with much lower agro-environmental endowment compared to stable croplands from 1990 to 2010. In sum, we found that cropland production potentials of the currently uncultivated areas are

  12. Impact of long-term N, P, K, and NPK fertilization on the composition and potential functions of the bacterial community in grassland soil.

    PubMed

    Pan, Yao; Cassman, Noriko; de Hollander, Mattias; Mendes, Lucas W; Korevaar, Hein; Geerts, Rob H E M; van Veen, Johannes A; Kuramae, Eiko E

    2014-10-01

    Soil abiotic and biotic interactions govern important ecosystem processes. However, the mechanisms behind these interactions are complex, and the links between specific environmental factors, microbial community structures, and functions are not well understood. Here, we applied DNA shotgun metagenomic techniques to investigate the effect of inorganic fertilizers N, P, K, and NPK on the bacterial community composition and potential functions in grassland soils in a 54-year experiment. Differences in total and available nutrients were found in the treatment soils; interestingly, Al, As, Mg, and Mn contents were variable in N, P, K, and NPK treatments. Bacterial community compositions shifted and Actinobacteria were overrepresented under the four fertilization treatments compared to the control. Redundancy analysis of the soil parameters and the bacterial community profiles showed that Mg, total N, Cd, and Al were linked to community variation. Using correlation analysis, Acidobacteria, Bacteroidetes, and Verrucomicrobia were linked similarly to soil parameters, and Actinobacteria and Proteobacteria were linked separately to different suites of parameters. Surprisingly, we found no fertilizers effect on microbial functional profiles which supports functional redundancy as a mechanism for stabilization of functions during changes in microbial composition. We suggest that functional profiles are more resistant to environmental changes than community compositions in the grassland ecosystem. PMID:25046442

  13. Long-term increases in BK potassium channel underlie increased action potential firing in dentate granule neurons following pilocarpine-induced status epilepticus in rats.

    PubMed

    Mehranfard, Nasrin; Gholamipour-Badie, Hamid; Motamedi, Fereshteh; Janahmadi, Mahyar; Naderi, Nima

    2015-01-12

    Temporal lobe epilepsy (TLE) is the most common form of acquired epilepsy in adult. Since dentate gyrus granule cells (GCs) play a critical role in hippocampal seizure generation, it is, therefore, important to understand changes in intrinsic properties of GCs in TLE. In this study, the electrophysiological properties of GCs obtained from epileptic rates were compared with the control group using whole cell patch-clamp recording. Results indicated a significant increase in the number of action potentials (APs) in depolarizing currents of 150 pA, 200 pA, and 250 pA. In addition, there was a significant decrease in AP half-width of GCs. The amplitude of fast afterhyperpolarization (fAHP) in epileptic group significantly decreased compared to control group. Blockade of large conductance calcium activated potassium channel (BK), channels with paxilline and iberiotoxin reversed pilocarpine-induced changes in electrophysiological properties of GCs in epileptic group. These results suggest that the BK channel blockers by reversing the firing properties of GCs might have beneficial preventative effects on pilocarpine-induced electrophysiological changes.

  14. Impact of long-term N, P, K, and NPK fertilization on the composition and potential functions of the bacterial community in grassland soil.

    PubMed

    Pan, Yao; Cassman, Noriko; de Hollander, Mattias; Mendes, Lucas W; Korevaar, Hein; Geerts, Rob H E M; van Veen, Johannes A; Kuramae, Eiko E

    2014-10-01

    Soil abiotic and biotic interactions govern important ecosystem processes. However, the mechanisms behind these interactions are complex, and the links between specific environmental factors, microbial community structures, and functions are not well understood. Here, we applied DNA shotgun metagenomic techniques to investigate the effect of inorganic fertilizers N, P, K, and NPK on the bacterial community composition and potential functions in grassland soils in a 54-year experiment. Differences in total and available nutrients were found in the treatment soils; interestingly, Al, As, Mg, and Mn contents were variable in N, P, K, and NPK treatments. Bacterial community compositions shifted and Actinobacteria were overrepresented under the four fertilization treatments compared to the control. Redundancy analysis of the soil parameters and the bacterial community profiles showed that Mg, total N, Cd, and Al were linked to community variation. Using correlation analysis, Acidobacteria, Bacteroidetes, and Verrucomicrobia were linked similarly to soil parameters, and Actinobacteria and Proteobacteria were linked separately to different suites of parameters. Surprisingly, we found no fertilizers effect on microbial functional profiles which supports functional redundancy as a mechanism for stabilization of functions during changes in microbial composition. We suggest that functional profiles are more resistant to environmental changes than community compositions in the grassland ecosystem.

  15. Long-Term Planning in Higher Education.

    ERIC Educational Resources Information Center

    United Nations Educational, Scientific and Cultural Organization, Bangkok (Thailand). Principal Regional Office for Asia and the Pacific.

    This report presents the concepts and issues discussed at a Regional Symposium on Long-term Planning in Higher Education held in Dhaka, Bangladesh, September 21-30, 1986. Chapter 1 explores some fundamental issues about the rationale for the objectives of long-term planning. It defines long-term planning in higher education, considers its…

  16. A hierarchical porous bowl-like PLA@MSNs-COOH composite for pH-dominated long-term controlled release of doxorubicin and integrated nanoparticle for potential second treatment.

    PubMed

    Pan, Jianming; Wu, Runrun; Dai, Xiaohui; Yin, Yijie; Pan, Guoqing; Meng, Minjia; Shi, Weidong; Yan, Yongsheng

    2015-04-13

    We chemically integrated mesoporous silica nanoparticles (MSNs) and macroporous bowl-like polylactic acid (pBPLA) matrix, for noninvasive electrostatic loading and long-term controlled doxorubicin (DOX) release, to prepare a hierarchical porous bowl-like pBPLA@MSNs-COOH composite with a nonspherical and hierarchical porous structure. Strong electrostatic interaction with DOX rendered excellent encapsulation efficiency (up to 90.14%) to the composite. DOX release showed pH-dominated drug release kinetics; thus, maintaining a weak acidic pH (e.g., 5.0) triggered sustained release, suggesting the composite's great potential for long-term therapeutic approaches. In-vitro cell viability assays further confirmed that the composite was biocompatible and that the loaded drugs were pharmacologically active, exhibiting dosage-dependent cytotoxicity. Additionally, a wound-healing assay revealed the composite's intrinsic ability to inhibit cell migration. Moreover, pH- and time-dependent leaching of the integrated MSNs due to pBPLA matrix degradation allow us to infer that the leached (and drug loaded) MSNs may be engulfed by cancer cells contributing to a second wave of DOX-mediated cytotoxicity following pH-triggered DOX release.

  17. Long-term aerosol and trace gas measurements in Eastern Lapland, Finland: the impact of Kola air pollution to new particle formation and potential CCN

    NASA Astrophysics Data System (ADS)

    Kyrö, Ella-Maria; Väänänen, Riikka; Kerminen, Veli-Matti; Virkkula, Aki; Asmi, Ari; Nieminen, Tuomo; Dal Maso, Miikka; Petäjä, Tuukka; Keronen, Petri; Aalto, Pasi; Riipinen, Ilona; Lehtipalo, Katrianne; Hari, Pertti; Kulmala, Markku

    2014-05-01

    Sulphur and primary emissions have been decreasing largely all over Europe, resulting in improved air quality and decreased direct radiation forcing by aerosols. The smelter industry in Kola Peninsula is one of largest sources of anthropogenic SO2 within the Arctic domain and since late 1990s the sulphur emissions have been decreasing rapidly (Paatero et al., 2008; Prank et al., 2010). New particle formation (NPF) is tightly linked with the oxidizing product of SO2, namely sulphuric acid (H2SO4), since it is known to be the key component in atmospheric nucleation (Sipilä et al., 2010). Thus, decreasing sulphur pollution may lead to less NPF. However, low values of condensation sink (CS), which is determined by the amount of pre-existing particles, favours NPF. We used 14 years (1998-2011) of aerosol number size distribution and trace gas data from SMEAR I station in Eastern Lapland, Finland, to investigate these relationships between SO2, NPF and CS. The station is a clean background station with occasional sulphur pollution episodes when the air masses arrive over Kola Peninsula. We found that while SO2 decreased by 11.3 % / year, the number of clear NPF event days was also decreasing by 9.9 % / year. At the same time, CS was decreasing also (-8.0 % / year) leading to formation of more particles per single NPF event (J3 increased by 29.7 % / year in 2006-2011) but the low vapour concentrations of H2SO4 (proxy decreased by 6.2 % / year) did not allow them to grow into climatically relevant sizes. Over the time, concentrations of potential CCN (cloud condensing nuclei) were also decreasing with more moderate pace, -4.0 % / year. The events started on average earlier after sunrise when the SO2 concentration during the start of the event was higher and NPF occurred more frequently in air masses which were travelling over Kola. Despite the total decrease in sulphur pollution originating from Kola there is currently no evidence of cleaning of the emissions, rather the

  18. Long-term effects of dynamic aortomyoplasty.

    PubMed

    Chachques, J C; Haab, F; Cron, C; Fischer, E C; Grandjean, P; Bruneval, P; Acar, C; Jebara, V A; Fontaliran, F; Carpentier, A F

    1994-07-01

    Aortomyoplasty consists of wrapping the latissimus dorsi muscle (LDM) around the ascending aorta and electrostimulating it during diastole. The ascending aorta will act as an ectopic neo-ventricle compressed during diastole, thus reproducing the effects of long-term diastolic counterpulsation. In 5 goats, the right LDM was transferred to the thoracic cavity after removal of the second rib. The ascending aorta was enlarged by a pericardial patch and wrapped with the LDM. Postoperative electrostimulation was delivered in a counterpulsating manner. Hemodynamic studies were performed at 12 and 24 months postoperatively. Percent increase in the subendocardial viability index (diastolic pressure-time index/systolic tension-time index) was calculated using unassisted and assisted cardiac cycles with the stimulator off versus the stimulator on at a 1:1 ratio in the basal state and after acute heart failure was induced by the administration of high doses of propranolol hydrochloride. Diastolic counterpulsation of the ascending aorta resulted in significant improvement in the subendocardial viability index long term, both in basal state conditions and after induced cardiac failure. During heart failure, aortomyoplasty increased the cardiac output and decreased systemic vascular resistance. Histopathologic studies up to 24 months showed preservation of the histologic structure of the aortic wall and no evidence of thromboembolism. Tight adhesions developed between the aortic wall (including the pericardial patch) and the LDM. The diameters of the enlarged aortas showed no significant differences compared with diameters immediately postoperatively. In conclusion, aortomyoplasty produces chronic diastolic augmentation with preservation of aortic structure. After induction of heart failure, aortomyoplasty offers efficient circulatory support.

  19. Rapid and long-term induction of effector immediate early genes (BDNF, Neuritin and Arc) in peri-infarct cortex and dentate gyrus after ischemic injury in rat brain.

    PubMed

    Rickhag, Mattias; Teilum, Maria; Wieloch, Tadeusz

    2007-06-01

    The genomic response following brain ischemia is very complex and involves activation of both protective and detrimental signaling pathways. Immediate early genes (IEGs) represent the first wave of gene expression following ischemia and are induced in extensive regions of the ischemic brain including cerebral cortex and hippocampus. Brain-derived neurotrophic factor (BDNF), Neuritin and Activity-regulated cytoskeleton-associated protein (Arc) belong to a subgroup of immediate early genes implicated in synaptic plasticity known as effector immediate early genes. Here, we investigated the spatial and temporal activation pattern for these genes during the first 24 h of reperfusion following 2-h occlusion of the middle cerebral artery. Neuritin showed a persistent activation in frontal-cingulate cortex while Arc displayed a biphasic response. Also, in dentate gyrus, activation was observed at 0-6 h of reperfusion for Neuritin and 0-12 h of reperfusion for Arc while BDNF was induced 0-9 h of reperfusion. Our study demonstrates a rapid and long-term activation of effector immediate early genes in distinct brain areas following ischemic injury in rat. Effector gene activation may be part of long-term synaptic responses of ischemic brain tissue. PMID:17397810

  20. Space ventures and society long-term perspectives

    NASA Technical Reports Server (NTRS)

    Brown, W. M.

    1985-01-01

    A futuristic evaluation of mankind's potential long term future in space is presented. Progress in space will not be inhibited by shortages of the Earth's physical resources, since long term economic growth will be focused on ways to constrain industrial productivity by changing social values, management styles, or government competence. Future technological progress is likely to accelerate with an emphasis on international cooperation, making possible such large joint projects as lunar colonies or space stations on Mars. The long term future in space looks exceedingly bright even in relatively pessimistic scenarios. The principal driving forces will be technological progress, commercial and public-oriented satellites, space industrialization, space travel, and eventually space colonization.

  1. Optical quantal analysis indicates that long-term potentiation at single hippocampal mossy fiber synapses is expressed through increased release probability, recruitment of new release sites, and activation of silent synapses.

    PubMed

    Reid, Christopher A; Dixon, Don B; Takahashi, Michiko; Bliss, Tim V P; Fine, Alan

    2004-04-01

    It is generally believed that long-term potentiation (LTP) at hippocampal mossy fiber synapses between dentate granule and CA3 pyramidal cells is expressed through presynaptic mechanisms leading to an increase in quantal content. The source of this increase has remained undefined but could include enhanced probability of transmitter release at existing functional release sites or increases in the number of active release sites. We performed optical quantal analyses of transmission at individual mossy fiber synapses in cultured hippocampal slices, using confocal microscopy and intracellular fluorescent Ca(2+) indicators. Our results indicate that LTP is expressed at functional synapses by both increased probability of transmitter release and recruitment of new release sites, including the activation of previously silent synapses here visualized for the first time.

  2. The neuronal response at extended timescales: long-term correlations without long-term memory

    PubMed Central

    Soudry, Daniel; Meir, Ron

    2014-01-01

    Long term temporal correlations frequently appear at many levels of neural activity. We show that when such correlations appear in isolated neurons, they indicate the existence of slow underlying processes and lead to explicit conditions on the dynamics of these processes. Moreover, although these slow processes can potentially store information for long times, we demonstrate that this does not imply that the neuron possesses a long memory of its input, even if these processes are bidirectionally coupled with neuronal response. We derive these results for a broad class of biophysical neuron models, and then fit a specific model to recent experiments. The model reproduces the experimental results, exhibiting long term (days-long) correlations due to the interaction between slow variables and internal fluctuations. However, its memory of the input decays on a timescale of minutes. We suggest experiments to test these predictions directly. PMID:24744724

  3. Long-term solar-terrestrial observations

    NASA Technical Reports Server (NTRS)

    1988-01-01

    The results of an 18-month study of the requirements for long-term monitoring and archiving of solar-terrestrial data is presented. The value of long-term solar-terrestrial observations is discussed together with parameters, associated measurements, and observational problem areas in each of the solar-terrestrial links (the sun, the interplanetary medium, the magnetosphere, and the thermosphere-ionosphere). Some recommendations are offered for coordinated planning for long-term solar-terrestrial observations.

  4. Design of a potential long-term test of gas production from a hydrate deposit at the PBU-L106 site in North Slope, Alaska: Geomechanical system response and seismic monitoring

    NASA Astrophysics Data System (ADS)

    Chiaramonte, L.; Kowalsky, M. B.; Rutqvist, J.; Moridis, G. J.

    2009-12-01

    In an effort to optimize the design of a potential long-term production test at the PBU-L106 site in North Slope, Alaska, we have developed a coupled modeling framework that includes the simulation of (1) large-scale production at the test site, (2) the corresponding geomechanical changes in the system caused by production, and (3) time-lapse geophysical (seismic) surveys. The long-term test is to be conducted within the deposit of the C-layer, which extends from a depth of 2226 to 2374 ft, and is characterized by two hydrate-bearing strata separated by a 30 ft shale interlayer. In this study we examine the expected geomechanical response of the permafrost-associated hydrate deposit (C-Layer) at the PBU L106 site during depressurization-induced production, and assess the potential for monitoring the system response with seismic measurements. Gas hydrates increase the strength of the sediments (often unconsolidated) they impregnate. Thus hydrate disassociation in the course of gas production could potentially affect the geomechanical stability of such deposits, leading to sediment failure and potentially affecting wellbore stability and integrity at the production site and/or at neighboring conventional production facilities. For the geomechanical analysis we use a coupled hydraulic, thermodynamic and geomechanical model (TOUGH+HYDRATE+FLAC3D, T+H+F for short) simulating production from a single vertical well at the center of an infinite-acting hydrate deposit. We investigate the geomechanical stability of the C-Layer, well stability and possible interference (due to production) with pre-existing wells in the vicinity, as well as the system sensitivity to important parameters (saturation, permeability, porosity and heterogeneity). The time-lapse seismic surveys are simulated using a finite-difference elastic wave propagation model that is linked to the T+H+F code. The seismic properties, such as the elastic and shear moduli, are a function of the simulated time- and

  5. Safety of long-term PPI therapy.

    PubMed

    Reimer, Christina

    2013-06-01

    Proton pump inhibitors have become the mainstay of medical treatment of acid-related disorders. Long-term use is becoming increasingly common, in some cases without a proper indication. A large number of mainly observational studies on a very wide range of possible associations have been published in the past decade and are critically reviewed in this article and the existing evidence is evaluated and translated into possible clinical consequences. Based on the existing evidence the benefits of PPI treatment seem to outweigh potential risks in the large majority of patients especially if PPI use is based on a relevant indication. The concern for complications should primarily be directed at elderly, malnourished with significant co-morbidity. In this population an increased risk for enteric infections, fractures and nutritional deficiencies might have clinical consequences and should lead to a careful evaluation of the indication for PPI treatment. PMID:23998981

  6. Dopaminergic modulation of long-term synaptic plasticity in rat prefrontal neurons.

    PubMed

    Otani, Satoru; Daniel, Hérve; Roisin, Marie-Paule; Crepel, Francis

    2003-11-01

    In rat prefrontal cortex (the prelimbic area of medial frontal cortex), the induction of long-term depression (LTD) and long-term potentiation (LTP) of glutamatergic synapses is powerfully modulated by dopamine. The presence of dopamine in the bathing medium facilitates LTD in slice preparations, whereas in the anesthetized intact brain, dopamine released from dopaminergic axon terminals in the prefrontal cortex facilitates LTP. Dopaminergic facilitation of LTD is at least partly achieved by postsynaptic biochemical mechanisms in which enzymatic processes triggered by dopamine receptor activation cooperate with those triggered by glutamate metabotropic receptor activation. Evidence suggests that dopamine facilitates LTP also in the slice condition. In this case, dopamine receptors must be pre-stimulated ('primed') before the application of high-frequency stimuli in the presence of dopamine. This procedure may mimic baseline stimulation of dopamine receptors that occurs under physiological conditions.

  7. The T-type voltage-gated calcium channel as a molecular target of the novel cognitive enhancer ST101: enhancement of long-term potentiation and CaMKII autophosphorylation in rat cortical slices.

    PubMed

    Moriguchi, Shigeki; Shioda, Norifumi; Yamamoto, Yui; Tagashira, Hideaki; Fukunaga, Kohji

    2012-04-01

    In this study, we report that spiro[imidazo[1,2-a]pyridine-3,2-indan]-2(3H)-one (ST101; previously coded as ZSET1446) targets T-type voltage-gated calcium channels in mediating improved cognition in the CNS. We prepared rat somatosensory cortical and hippocampal slices, treated them with 0.01 to 100 nM ST101, and performed immunoblotting and electrophysiological analyses using various voltage-gated calcium channel (VGCC) inhibitors. Treatment of rat cortical slices with a range of ST101 concentrations significantly increased calcium/calmodulin-dependent protein kinase II (CaMKII) autophosphorylation following a bell-shaped dose-response curve, with 0.1 nM ST101 representing the maximally effective concentration. protein kinase Cα autophosphorylation was also significantly increased by 0.1 nM ST101 treatment. ST101 treatment had a moderate effect on CaMKII autophosphorylation but no effect on hippocampal protein kinase Cα autophosphorylation in slice preparations. Consistent with increased cortical CaMKII autophosphorylation, AMPA-type glutamate receptor subunit 1 (Ser-831) phosphorylation as a CaMKII post-synaptic substrate was significantly increased by treatment with 0.1-1 nM ST101, whereas phosphorylation of the pre-synaptic substrate synapsin I (Ser-603) remained unchanged. Notably, enhanced CaMKII autophosphorylation seen following 0.1 nM ST101 treatment was significantly inhibited by pre-treatment with 1 μM mibefradil, a T-type VGCC inhibitor, but not with N-type (ω-conotoxin), P/Q-type (ω-agatoxin) or L-type (nifedipine) VGCC inhibitors. Similarly, 0.1 nM ST101 significantly potentiated long-term potentiation in cortical but not hippocampal slices. Enhanced long-term potentiation in cortical slices was totally inhibited by 1 μM mibefadil treatment. Finally, whole-cell patch-clamp analysis of Neuro2A cells over-expressing recombinant human Ca(V) 3.1 (α1G) T-channels and treated with 0.1 nM ST101 showed significant increases in T-type VGCC currents

  8. Scientific Understanding from Long Term Observations: Insights from the Long Term Ecological Research (LTER) Program

    NASA Astrophysics Data System (ADS)

    Gosz, J.

    2001-12-01

    estuaries below by removing all incoming freshwater. At Toolik Lake, long-term experiments of removing top predators from the good web of lakes showed dramatic alterations of lake populations of small fish and zooplankton. In New Mexico, LTER research on small mammal populations is successfully predicting rodent increases and the potential for increased zoonotic diseases such as Hantavirus and bubonic plague. This ability to forecast based on El Nino prediction is being used to increase scientific awareness and public health awareness through media based communication with the public. In Oregon, the Andrews Forest LTER program has had long, strong links with natural resource policy and management. Basic understanding of forest-stream interactions, characteristics of old-growth forests, roles of woody debris in temperate forest ecosystems, invertebrate biodiversity and ecosystem function have been incorporated in management guidelines, plans and regulations for public and private lands throughout the Pacific Northwest. Other examples of the values of long-term research and monitoring will be presented.

  9. Financing long-term care in Canada.

    PubMed

    Jacobs, P; Mills, C; Hollander, M

    1997-06-01

    Financial policies relating to long-term care in Canada are changing rapidly in response to demands for health care reform. This chapter focuses on the financial structure of institutional care, primarily nursing homes, in the western provinces of Alberta and British Columbia. Community-based long-term care is discussed briefly.

  10. Long-term preservation of Anammox bacteria

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Deposit of useful microorganisms in culture collections requires long-term preservation and successful reactivation techniques. The goal of this study was to develop a simple preservation protocol for the long-term storage and reactivation of the anammox biomass. To achieve this, anammox biomass w...

  11. Paying for long-term care.

    PubMed Central

    Estes, C L; Bodenheimer, T

    1994-01-01

    Everyone agrees that insurance for long-term care is inadequate in the United States. Disagreement exists, however, on whether such insurance should be provided through the private or public sector. Private insurance generally uses the experience-rating principle that persons with higher risk of illness are charged higher premiums. For private insurance for long-term care, this principle creates a dilemma. Most policies will be purchased by the elderly; yet, because the elderly have a high risk of needing long-term care, only about 20% of them can afford the cost of premiums. A public-private partnership by which the government partially subsidizes private long-term-care insurance is unlikely to resolve this dilemma. Only a social insurance program for long-term care can provide universal, affordable, and equitable coverage. PMID:8128712

  12. Proteasome Modulates Positive and Negative Translational Regulators in Long-Term Synaptic Plasticity

    PubMed Central

    Dong, Chenghai; Bach, Svitlana V.; Haynes, Kathryn A.

    2014-01-01

    Proteolysis by the ubiquitin-proteasome pathway appears to have a complex role in synaptic plasticity, but its various functions remain to be elucidated. Using late phase long-term potentiation (L-LTP) in the hippocampus of the mouse as a model for long-term synaptic plasticity, we previously showed that inhibition of the proteasome enhances induction but blocks maintenance of L-LTP. In this study, we investigated the possible mechanisms by which proteasome inhibition has opposite effects on L-LTP induction and maintenance. Our results show that inhibiting phosphatidyl inositol-3 kinase or blocking the interaction between eukaryotic initiation factors 4E (eIF4E) and 4G (eIF4G) reduces the enhancement of L-LTP induction brought about by proteasome inhibition suggesting interplay between proteolysis and the signaling pathway mediated by mammalian target of rapamycin (mTOR). Also, proteasome inhibition leads to accumulation of translational activators in the mTOR pathway such as eIF4E and eukaryotic elongation factor 1A (eEF1A) early during L-LTP causing increased induction. Furthermore, inhibition of the proteasome causes a buildup of translational repressors, such as polyadenylate-binding protein interacting protein 2 (Paip2) and eukaryotic initiation factor 4E-binding protein 2 (4E-BP2), during late stages of L-LTP contributing to the blockade of L-LTP maintenance. Thus, the proteasome plays a critical role in regulating protein synthesis during L-LTP by tightly controlling translation. Our results provide novel mechanistic insights into the interplay between protein degradation and protein synthesis in long-term synaptic plasticity. PMID:24573276

  13. Application of Micropatterned Cocultured Hepatocytes to Evaluate the Inductive Potential and Degradation Rate of Major Xenobiotic Metabolizing Enzymes.

    PubMed

    Dixit, Vaishali; Moore, Amanda; Tsao, Hong; Hariparsad, Niresh

    2016-02-01

    Long-term coculture models of hepatocytes are promising tools to study drug transport, clearance, and hepatoxicity. In this report we compare the basal expression of drug disposition genes and the inductive response of prototypical inducers (rifampin, phenobarbital, phenytoin) in hepatocyte two-dimensional monocultures and the long-term coculture model (HepatoPac). All the inducers used in the study increased the expression and activity of CYP3A4, CYP2B6 and CYP2C enzymes in the HepatoPac cultures. The coculture model showed a consistent and higher induction of CYP2C enzymes compared with the monocultures. The EC50 of rifampin for CYP3A4 and CYP2C9 was up to 10-fold lower in HepatoPac than the monocultures. The EC50 of rifampin calculated from the clinical drug interaction studies correlated well with the EC50 observed in the HepatoPac cultures. Owing to the long-term stability of the HepatoPac cultures, we were able to directly measure a half-life (t1/2) for both CYP3A4 and CYP2B6 using the depletion kinetics of mRNA and functional activity. The t1/2 for CYP3A4 mRNA was 26 hours and that for the functional protein was 49 hours. The t1/2 of CYP2B6 was 38 hours (mRNA) and 68 hours (activity), which is longer than CYP3A4 and shows the differential turnover of these two proteins. This is the first study to our knowledge to report the turnover rate of CYP2B6 in human hepatocytes. The data presented here demonstrate that the HepatoPac cultures have the potential to be used in long-term culture to mimic complex clinical scenarios. PMID:26658225

  14. Loss of epidermal integrity by T cell-mediated attack induces long-term local resistance to subsequent attack. I. Induction of resistance correlates with increases in Thy-1+ epidermal cell numbers

    PubMed Central

    1990-01-01

    The cutaneous graft-versus-host disease (GVHD) lesions induced by intradermal injection of cloned autoreactive T cells have been shown to subside rapidly and the epidermis returns to normal 2 wk after injection. Those mice that had spontaneously recovered from the cutaneous GVHD became resistant to subsequent attempts to induce the cutaneous GVHD by the T cells while maintaining their activity to mount delayed-type hypersensitivity (DTH) responses and to induce the enlargement of the popliteal lymph nodes (PLN). The resistance appeared to be restricted to the epidermal structures of the injection sites, suggesting the involvement of locally acting suppression mechanisms. This local resistance was not specific for the clonotype used for the induction of the resistance. A loss of the epidermal integrity by an attack of T cells capable of producing cutaneous GVHD was a prerequisite for the induction of the resistance. By up to at least 8 mo after injection of the T cells, no mice became susceptible to the cutaneous GVHD again, provided that the T cells were injected into the same footpad sites that had initially received the T cells. This resistance correlated well with the great increase (20-30-fold) in Thy- 1+ EC number. The great increase in the number of Thy-1+ EC following destruction of epidermal structures may be important in protecting the epidermal integrity from an additional attack by T cells. PMID:1969918

  15. Short-term effects on antioxidant enzymes and long-term genotoxic and carcinogenic potential of CuO nanoparticles compared to bulk CuO and ionic copper in mussels Mytilus galloprovincialis.

    PubMed

    Ruiz, Pamela; Katsumiti, Alberto; Nieto, Jose A; Bori, Jaume; Jimeno-Romero, Alba; Reip, Paul; Arostegui, Inmaculada; Orbea, Amaia; Cajaraville, Miren P

    2015-10-01

    The aim of this work was to study short-term effects on antioxidant enzyme activities and long-term genotoxic and carcinogenic potential of CuO nanoparticles (NPs) in comparison to bulk CuO and ionic copper in mussels Mytilus galloprovincialis after 21 days exposure to 10 μg Cu L(-1). Then, mussels were kept for up to 122 days in clean water. Cu accumulation depended on the form of the metal and on the exposure time. CuO NPs were localized in lysosomes of digestive cells, as confirmed by TEM and X ray microanalysis. CuO NPs, bulk CuO and ionic copper produced different effects on antioxidant enzyme activities in digestive glands, overall increasing antioxidant activities. CuO NPs significantly induced catalase and superoxide dismutase activities. Fewer effects were observed in gills. Micronuclei frequency increased significantly in mussels exposed to CuO NPs and one organism treated with CuO NPs showed disseminated neoplasia. However, transcription levels of cancer-related genes did not vary significantly. Thus, short-term exposure to CuO NPs provoked oxidative stress and genotoxicity, but further studies are needed to determine whether these early events can lead to cancer development in mussels.

  16. Chronic sodium salicylate administration enhances population spike long-term potentiation following a combination of theta frequency primed-burst stimulation and the transient application of pentylenetetrazol in rat CA1 hippocampal neurons.

    PubMed

    Gholami, Masoumeh; Moradpour, Farshad; Semnanian, Saeed; Naghdi, Nasser; Fathollahi, Yaghoub

    2015-11-15

    The effect of chronic administration of sodium salicylate (NaSal) on the excitability and synaptic plasticity of the rodent hippocampus was investigated. Repeated systemic treatment with NaSal reliably induced tolerance to the anti-nociceptive effect of NaSal (one i.p. injection per day for 6 consecutive days). Following chronic NaSal or vehicle treatment, a series of electrophysiological experiments on acute hippocampal slices (focusing on the CA1 circuitry) were tested whether tolerance to NaSal would augment pentylenetetrazol (PTZ)-induced long-term potentiation (LTP) and /or epileptic activity, and whether the augmentation was the same after priming activity with a natural stimulus pattern prior to PTZ. We noted an altered synaptic input-to-spike transformation, such that neuronal firing increased after a given synaptic drive. Population spike-LTP (PS-LTP) was increased in the NaSal-tolerant animals, but only when it was induced via a combination of electrical stimulation (theta pattern primed-burst stimulation) and the transient application of PTZ. Identifying and understanding these changes in neuronal excitability and synaptic plasticity following chronic salicylate treatment could prove useful in the clinical diagnosis or treatment of chronic aspirin-induced, or even idiopathic, seizure activity.

  17. The molecular cascades of long-term potentiation underlie memory consolidation of one-trial avoidance in the CA1 region of the dorsal hippocampus, but not in the basolateral amygdala or the neocortex.

    PubMed

    Izquierdo, Iván; Bevilaqua, Lia R M; Rossato, Janine I; da Silva, Weber C; Bonini, Juliana; Medina, Jorge H; Cammarota, Martín

    2008-10-01

    Data accumulated through the past 15 years showed that memory consolidation of one-trial avoidance learning relies on a sequence of molecular events in the CA1 region of the hippocampus that is practically identical to that of long-term potentiation (LTP) in that area. Recent findings have indeed described CA1 LTP concomitant to the consolidation of this and other tasks. However, abundant evidence suggests that, in addition, other molecular events, involving some of the same steps but with different timing and in different sequence in the basolateral amygdala, entorhinal, parietal and cingulate cortex are as important as those of the hippocampus for memory consolidation. Here we review the hippocampal mechanisms involved and the possible interconnections between all these processes. Overall, the findings indicate that memory consolidation of even a task as deceivingly simple as one-trial avoidance relies on hippocampal LTP but also requires the concomitant participation of other brain systems and molecular events. Further, they point to the mechanisms that account for the enhanced consolidation usually seen for emotion-laden memories.

  18. Methylphenidate amplifies long-term potentiation in rat hippocampus CA1 area involving the insertion of AMPA receptors by activation of β-adrenergic and D1/D5 receptors.

    PubMed

    Rozas, C; Carvallo, C; Contreras, D; Carreño, M; Ugarte, G; Delgado, R; Zeise, M L; Morales, B

    2015-12-01

    Methylphenidate (MPH, Ritalin©) is widely used in the treatment of Attention Deficit Hyperactivity Disorder and recently as a drug of abuse. Although the effect of MPH has been studied in brain regions such as striatum and prefrontal cortex (PFC), the hippocampus has received relatively little attention. It is known that MPH increases the TBS-dependent Long Term Potentiation (LTP) in the CA1 area. However, the cellular and molecular mechanisms involved in this process are still unknown. Using field potential recordings and western blot analysis in rat hippocampal slices of young rats, we found that acute application of MPH enhances LTP in CA3-CA1 synapses in a dose-dependent manner with an EC50 of 73.44±6.32 nM. Using specific antagonists and paired-pulse facilitation protocols, we observed that the MPH-dependent increase of LTP involves not only β-adrenergic receptors activation but also post-synaptic D1/D5 dopamine receptors. The inhibition of PKA with PKI, suppressed the facilitation of LTP induced by MPH consistent with an involvement of the adenyl cyclase-cAMP-PKA dependent cascade downstream of the activation of D1/D5 receptors. In addition, samples of CA1 areas taken from slices potentiated with MPH presented an increase in the phosphorylation of the Ser845 residue of the GluA1 subunit of AMPA receptors compared to control slices. This effect was reverted by SCH23390, antagonist of D1/D5 receptors, and PKI. Moreover, we found an increase of surface-associated functional AMPA receptors. We propose that MPH increases TBS-dependent LTP in CA3-CA1 synapses through a polysynaptic mechanism involving activation of β-adrenergic and D1/D5 dopaminergic receptors and promoting the trafficking and insertion of functional AMPA receptors to the plasma membrane.

  19. Neurological long term consequences of deep diving.

    PubMed

    Todnem, K; Nyland, H; Skeidsvoll, H; Svihus, R; Rinck, P; Kambestad, B K; Riise, T; Aarli, J A

    1991-04-01

    Forty commercial saturation divers, mean age 34.9 (range 24-49) years, were examined one to seven years after their last deep dive (190-500 metres of seawater). Four had by then lost their divers' licence because of neurological problems. Twenty seven (68%) had been selected by neurological examination and electroencephalography before the deep dives. The control group consisted of 100 men, mean age 34.0 (range 22-48) years. The divers reported significantly more symptoms from the nervous system. Concentration difficulties and paraesthesia in feet and hands were common. They had more abnormal neurological findings by neurological examination compatible with dysfunction in the lumbar spinal cord or roots. They also had a larger proportion of abnormal electroencephalograms than the controls. The neurological symptoms and findings were highly significantly correlated with exposure to deep diving (depth included), but even more significantly correlated to air and saturation diving and prevalence of decompression sickness. Visual evoked potentials, brainstem auditory evoked potentials, and magnetic resonance imaging of the brain did not show more abnormal findings in the divers. Four (10%) divers had had episodes of cerebral dysfunction during or after the dives; two had had seizures, one had had transitory cerebral ischaemia and one had had transitory global amnesia. It is concluded that deep diving may have a long term effect on the nervous system of the divers.

  20. LONG-TERM MONITORING SENSOR NETWORK

    SciTech Connect

    Stephen P. Farrington; John W. Haas; Neal Van Wyck

    2003-10-16

    Long-term monitoring (LTM) associated with subsurface contamination sites is a key element of Long Term Stewardship and Legacy Management across the Department of Energy (DOE) complex. However, both within the DOE and elsewhere, LTM is an expensive endeavor, often exceeding the costs of the remediation phase of a clean-up project. The primary contributors to LTM costs are associated with labor. Sample collection, storage, preparation, analysis, and reporting can add a significant financial burden to project expense when extended over many years. Development of unattended, in situ monitoring networks capable of providing quantitative data satisfactory to regulatory concerns has the potential to significantly reduce LTM costs. But survival and dependable operation in a difficult environment is a common obstacle to widespread use across the DOE complex or elsewhere. Deploying almost any sensor in the subsurface for extended periods of time will expose it to chemical and microbial degradation. Over the time-scales required for in situ LTM, even the most advanced sensor systems may be rendered useless. Frequent replacement or servicing (cleaning) of sensors is expensive and labor intensive, offsetting most, if not all, of the cost savings realized with unattended, in situ sensors. To enable facile, remote monitoring of contaminants and other subsurface parameters over prolonged periods, Applied Research Associates, Inc has been working to develop an advanced LTM sensor network consisting of three key elements: (1) an anti-fouling sensor chamber that can accommodate a variety of chemical and physical measurement devices based on electrochemical, optical and other techniques; (2) two rapid, cost effective, and gentle means of emplacing sensor packages either at precise locations directly in the subsurface or in pre-existing monitoring wells; and (3) a web browser-based data acquisition and control system (WebDACS) utilizing field-networked microprocessor-controlled smart

  1. Long Term Effects of Food Poisoning

    MedlinePlus

    ... develop chronic arthritis. Brain and nerve damage A Listeria infection can lead to meningitis, an inflammation of ... brain. If a newborn infant is infected with Listeria , long-term consequences may include mental retardation, seizures, ...

  2. Asthma Medicines: Long-Term Control

    MedlinePlus

    ... Español Text Size Email Print Share Asthma Medicines: Long-term Control Page Content Article Body Corticosteroids Synthetic ... and sprinkle forms are available for young children. Long-Acting Beta2-Agonists Medications in the beta 2 - ...

  3. Vector Potential, Electromagnetic Induction and "Physical Meaning"

    ERIC Educational Resources Information Center

    Giuliani, G.

    2010-01-01

    A forgotten experiment by Andre Blondel (1914) proves, as held on the basis of theoretical arguments in a previous paper, that the time variation of the magnetic flux is not the cause of the induced emf; the physical agent is instead the vector potential through the term [equation omitted] (when the induced circuit is at rest). The "good…

  4. Long Term Outcomes after Pediatric Liver Transplantation

    PubMed Central

    2013-01-01

    Long term outcomes after liver transplantation are major determinants of quality of life and of the value of this heroic treatment. As short term outcomes are excellent, our community is turning to take a harder look at long term outcomes. The purpose of this paper is to review these outcomes, and highlight proposed treatments, as well as pressing topics needing to be studied. A systemic review of the English literature was carried in PubMed, covering all papers addressing long term outcomes in pediatric liver transplant from 2000-2013. Late outcomes after pediatric liver transplant affect the liver graft in the form of chronic liver dysfunction. The causes include rejection particularly humoral rejection, but also de novo autoimmune hepatitis, and recurrent disease. The metabolic syndrome is a major factor in long term cardiovascular complication risk. Secondary infections, kidney dysfunction and malignancy remain a reality of those patients. There is growing evidence of late cognitive and executive function delays affecting daily life productivity as well as likely adherence. Finally, despite a good health status, quality of life measures are comparable to those of children with chronic diseases. Long term outcomes are the new frontier in pediatric liver transplantation. Much is needed to improve graft survival, but also to avoid systemic morbidities from long term immunosuppression. Quality of life is a new inclusive measure that will require interventions and innovative approaches respectful not only on the patients but also of their social circle. PMID:24511516

  5. Differential effects of the histamine H3 receptor agonist methimepip on dentate granule cell excitability, paired-pulse plasticity and long-term potentiation in prenatal alcohol-exposed rats

    PubMed Central

    Varaschin, Rafael K.; Rosenberg, Martina J.; Hamilton, Derek A.; Savage, Daniel D.

    2016-01-01

    We previously reported that prenatal alcohol-induced deficits in dentate gyrus (DG) long-term potentiation (LTP) are ameliorated by the histamine H3 receptor inverse agonist ABT-239. ABT-239 did not enhance LTP in control rats, suggesting a heightened H3 receptor-mediated inhibition of glutamate release in prenatal alcohol-exposed (PAE) offspring. As the modulation of glutamate release is one important facet of LTP, we examined the effect of methimepip, a histamine H3 receptor agonist, on DG granule cell excitability, glutamate release and LTP in control and PAE rats. Long-Evans rat dams voluntarily consumed either a 0% or 5% ethanol solution four hours daily throughout gestation. Male adult offspring were anesthetized with urethane and electrodes implanted into the entorhinal cortex and DG. PAE reduced coupling of excitatory post-synaptic field potentials to population spikes, an effect mimicked in control rats treated with 1 mg/kg methimepip. Methimepip decreased release probability in controls but not in PAE offspring. GABAergic feedback inhibition of granule cell responsiveness was not affected by either PAE or methimepip. PAE reduced LTP in the DG, another effect mimicked in methimepip-treated control rats. Again, methimepip did not exacerbate the PAE-induced LTP deficit. Thus, while methimepip treatment of control rats mimicked some baseline and activity-dependent deficits observed in saline-treated PAE offspring, methimepip treatment of PAE rats did not exacerbate these deficits. Whether the absence of an added methimepip effect in PAE offspring is a consequence of a “floor effect” for the responses measured or is due to differential drug dose responsiveness will require further investigation. Further, more detailed studies of H3 receptor-mediated responses in vitro may provide clearer insights into the role of the H3 receptor regulation of excitatory transmission at the perforant path - DG synapse in PAE rats. PMID:24818819

  6. Transuranic waste: long-term planning

    SciTech Connect

    Young, K.C.

    1985-07-01

    Societal concerns for the safe handling and disposal of toxic waste are behind many of the regulations and the control measures in effect today. Transuranic waste, a specific category of toxic (radioactive) waste, serves as a good example of how regulations and controls impact changes in waste processing - and vice versa. As problems would arise with waste processing, changes would be instituted. These changes improved techniques for handling and disposal of transuranic waste, reduced the risk of breached containment, and were usually linked with regulatory changes. Today, however, we face a greater public awareness of and concern for toxic waste control; thus, we must anticipate potential problems and work on resolving them before they can become real problems. System safety analyses are valuable aids in long-term planning for operations involving transuranic as well as other toxic materials. Examples of specific system safety analytical methods demonstrate how problems can be anticipated and resolution initiated in a timely manner having minimal impacts upon allocation of resource and operational goals. 7 refs., 1 fig.

  7. Wnt signaling is required for long-term memory formation

    PubMed Central

    Tan, Ying; Yu, Dinghui; Busto, Germain U.; Wilson, Curtis; Davis, Ronald L.

    2013-01-01

    SUMMARY Wnt signaling regulates synaptic plasticity and neurogenesis in the adult nervous system, suggesting a potential role in behavioral processes. Here, we probed the requirement for Wnt signaling during olfactory memory formation in Drosophila using an inducible RNA interference approach. Interfering with β-catenin expression in the adult mushroom body neurons specifically impaired long-term memory without altering short-term memory. The impairment was reversible, rescued with expression of a wild-type β-catenin transgene, and correlated with a disruption of a cellular long-term memory trace. Inhibition of wingless, a Wnt ligand, and arrow, a Wnt co-receptor, also impaired long-term memory. Wingless expression in wild type flies was transiently elevated in the brain after long-term memory conditioning. Thus, inhibiting three key components of the Wnt signaling pathway in the adult mushroom bodies impairs long-term memory, collectively indicating that this pathway mechanistically underlies this specific form of memory. PMID:24035392

  8. Long-Term Prognosis of Ischemic Stroke in Young Adults

    PubMed Central

    Varona, Jose F.

    2011-01-01

    There is limited information about long-term prognosis of ischemic stroke in young adults. Giving the potentially negative impact in physical, social, and emoti