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Sample records for enhanced long-term depression

  1. 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

    2003-07-02

    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.

  2. Enhanced AMPA receptor function promotes cerebellar long-term depression rather than potentiation

    PubMed Central

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

    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 parallel fiber (PF) to Purkinje cell synapses, thus resembling CX546 effects described at hippocampal synapses. Using the fluorescent calcium indicator dye Oregon Green BAPTA-2 and an ultra-high-speed CCD camera, we also monitored calcium transients in Purkinje cell dendrites. In the presence of CX546 in the bath, PF-evoked calcium transients were enhanced and prolonged, suggesting that CX546 not only enhances synaptic transmission, but also boosts dendritic calcium signaling at cerebellar synapses. In contrast to previous observations in the hippocampus, however, CX546 applied during cerebellar recordings facilitates long-term depression (LTD) rather than LTP at PF synapses. These findings show that ampakines selectively modify the LTP–LTD balance depending on the brain area and type of synapse, and may provide tools for the targeted regulation of synaptic memories. PMID:25403454

  3. Enhanced AMPA receptor function promotes cerebellar long-term depression rather than potentiation.

    PubMed

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

    2014-12-01

    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 parallel fiber (PF) to Purkinje cell synapses, thus resembling CX546 effects described at hippocampal synapses. Using the fluorescent calcium indicator dye Oregon Green BAPTA-2 and an ultra-high-speed CCD camera, we also monitored calcium transients in Purkinje cell dendrites. In the presence of CX546 in the bath, PF-evoked calcium transients were enhanced and prolonged, suggesting that CX546 not only enhances synaptic transmission, but also boosts dendritic calcium signaling at cerebellar synapses. In contrast to previous observations in the hippocampus, however, CX546 applied during cerebellar recordings facilitates long-term depression (LTD) rather than LTP at PF synapses. These findings show that ampakines selectively modify the LTP-LTD balance depending on the brain area and type of synapse, and may provide tools for the targeted regulation of synaptic memories.

  4. 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…

  5. Acute food deprivation enhances fear extinction but inhibits long-term depression in the lateral amygdala via ghrelin signaling.

    PubMed

    Huang, Chiung-Chun; Chou, Dylan; Yeh, Che-Ming; Hsu, Kuei-Sen

    2016-02-01

    Fear memory-encoding thalamic input synapses to the lateral amygdala (T-LA) exhibit dynamic efficacy changes that are tightly correlated with fear memory strength. Previous studies have shown that auditory fear conditioning involves strengthening of synaptic strength, and conversely, fear extinction training leads to T-LA synaptic weakening and occlusion of long-term depression (LTD) induction. These findings suggest that the mechanisms governing LTD at T-LA synapses may determine the behavioral outcomes of extinction training. Here, we explored this hypothesis by implementing food deprivation (FD) stress in mice to determine its effects on fear extinction and LTD induction at T-LA synapses. We found that FD increased plasma acylated ghrelin levels and enhanced fear extinction and its retention. Augmentation of fear extinction by FD was blocked by pretreatment with growth hormone secretagogue receptor type-1a antagonist D-Lys(3)-GHRP-6, suggesting an involvement of ghrelin signaling. Confirming previous findings, two distinct forms of LTD coexist at thalamic inputs to LA pyramidal neurons that can be induced by low-frequency stimulation (LFS) or paired-pulse LFS (PP-LFS) paired with postsynaptic depolarization, respectively. Unexpectedly, we found that FD impaired the induction of PP-LFS- and group I metabotropic glutamate receptor agonist (S)-3,5-dihydroxyphenylglycine (DHPG)-induced LTD, but not LFS-induced LTD. Ghrelin mimicked the effects of FD to impair the induction of PP-LFS- and DHPG-induced LTD at T-LA synapses, which were blocked by co-application of D-Lys(3)-GHRP-6. The sensitivity of synaptic transmission to 1-naphthyl acetyl spermine was not altered by either FD or ghrelin treatment. These results highlight distinct features of fear extinction and LTD at T-LA synapses.

  6. Long-term prognosis of depression in primary care.

    PubMed Central

    Simon, G. E.

    2000-01-01

    This article uses longitudinal data from a primary care sample to examine long-term prognosis of depression. A sample of 225 patients initiating antidepressant treatment in primary care completed assessments of clinical outcome (Hamilton Depression Rating Scale and the mood module of the Structured Clinical Interview for DSM-IIIR) 1, 3, 6, 9, 12, 18 and 24 months after initiating treatment. The proportion of patients continuing to meet criteria for major depression fell rapidly to approximately 10% and remained at approximately that level throughout follow-up. The proportion meeting criteria for remission (Hamilton Depression score of 7 or less) rose gradually to approximately 45%. Long-term prognosis (i.e. probability of remission at 6 months and beyond) was strongly related to remission status at 3 months (odds ratio 3.65; 95% confidence interval, 2.81-4.76) and only modestly related to various clinical characteristics assessed at baseline (e.g. prior history of recurrent depression, medical comorbidity, comorbid anxiety symptoms). The findings indicate that potentially modifiable risk factors influence the long-term prognosis of depression. This suggests that more systematic and effective depression treatment programmes might have an important effect on long-term course and reduce the overall burden of chronic and recurrent depression. PMID:10885162

  7. Long-term treatment of major depressive disorder with paroxetine.

    PubMed

    Duboff, E A

    1993-12-01

    Recurrent unipolar depression is a common, but undertreated disorder. Many patients require long-term maintenance therapy, and full doses of antidepressant agents may be preferred for the prevention of relapse. We report results of a 1-year, multicenter, open-label study of paroxetine (10 to 50 mg/day) in 433 patients with major depressive disorder, with additional data from 110 patients who entered a long-term extension of the study. The primary measures of efficacy were the Hamilton Rating Scale for Depression (HAM-D) total and Clinical Global Impression (CGI) severity of illness scores. During the first 6 weeks of therapy, the mean HAM-D total declined approximately 50% (from 27.9 to 13.5), with continued improvement, at an attenuated rate, throughout the first year. At the end of 1 year, the mean HAM-D total was 6.9. Similarly, the CGI severity of illness score declined from 4.6 at baseline to 2.8 at week 6 and to 1.7 at the end of 1 year. Remission was maintained in the population that entered the long-term extension, with mean HAM-D total and CGI severity of illness scores of 6.4 and 1.8, respectively, after 2.5 years, and 4.2 and 1.3 after 4 years. The most common adverse events reported during long-term treatment with paroxetine were somnolence, nausea, headache, and sweating. Pharmacokinetic analysis showed no clear correlation between the concentrations of paroxetine in plasma and either clinical efficacy or tolerability. There was no increased drug accumulation during long-term treatment. Side effects tended to occur early during therapy; and no new side effects emerged during the long-term extension. These results suggest that paroxetine is effective and well tolerated in the long-term treatment of depression.

  8. 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

  9. Long-term depression of excitatory synaptic transmission and its relationship to long-term potentiation.

    PubMed

    Artola, A; Singer, W

    1993-11-01

    In many brain areas, including the cerebellar cortex, neocortex, hippocampus, striatum and nucleus accumbens, brief activation of an excitatory pathway can produce long-term depression (LTD) of synaptic transmission. In most preparations, induction of LTD has been shown to require a minimum level of postsynaptic depolarization and a rise in the intracellular Ca2+ concentration [Ca2+]i in the postsynaptic neurone. Thus, induction conditions resemble those described for the initiation of associative long-term potentiation (LTP). However, data from structures susceptible to both LTD and LTP suggest that a stronger depolarization and a greater increase in [Ca2+]i are required to induce LTP than to initiate LTD. The source of Ca2+ appears to be less critical for the differential induction of LTP and LTD than the amplitude of the Ca2+ surge, since the activation of voltage- and ligand-gated Ca2+ conductances as well as the release from intracellular stores have all been shown to contribute to both LTD and LTP induction. LTD is induceable even at inactive synapses if [Ca2+]i is raised to the appropriate level by antidromic or heterosynaptic activation, or by raising the extracellular Ca2+ concentration [Ca2+]o. These conditions suggest a rule (called here the ABS rule) for activity-dependent synaptic modifications that differs from the classical Hebb rule and that can account for both homosynaptic LTD and LTP as well as for heterosynaptic competition and associativity.

  10. Gating of long-term depression by Ca2+/calmodulin-dependent protein kinase II through enhanced cGMP signalling in cerebellar Purkinje cells

    PubMed Central

    Kawaguchi, Shin-ya; Hirano, Tomoo

    2013-01-01

    Long-term depression (LTD) at parallel fibre synapses on a cerebellar Purkinje cell has been regarded as a cellular basis for motor learning. Although Ca2+/calmodulin-dependent protein kinase II (CaMKII) has been implicated in the LTD induction as an important Ca2+-sensing molecule, the underlying signalling mechanism remains unclear. Here, we attempted to explore the potential signalling pathway underlying the CaMKII involvement in LTD using a systems biology approach, combined with validation by electrophysiological and FRET imaging experiments on a rat cultured Purkinje cell. Model simulation predicted the following cascade as a candidate mechanism for the CaMKII contribution to LTD: CaMKII negatively regulates phosphodiesterase 1 (PDE1), subsequently facilitates the cGMP/protein kinase G (PKG) signalling pathway and down-regulates protein phosphatase 2A (PP-2A), thus supporting the LTD-inducing positive feedback loop consisting of mutual activation of protein kinase C (PKC) and mitogen-activated protein kinase (MAPK). This model suggestion was corroborated by whole-cell patch clamp recording experiments. In addition, FRET measurement of intracellular cGMP concentration revealed that CaMKII activation causes sustained increase of cGMP, supporting the signalling mechanism of LTD induction by CaMKII. Furthermore, we found that activation of the cGMP/PKG pathway by nitric oxide (NO) can support LTD induction without activation of CaMKII. Thus, this study clarified interaction between NO and Ca2+/CaMKII, two important factors required for LTD. PMID:23297306

  11. Serotonin induces long-term depression at corticostriatal synapses.

    PubMed

    Mathur, Brian N; Capik, Nicole A; Alvarez, Veronica A; Lovinger, David M

    2011-05-18

    The striatum has important roles in motor control and action learning and, like many brain regions, receives multiple monoaminergic inputs. We have examined serotonergic modulation of rat and mouse corticostriatal neurotransmission and find that serotonin (5-HT) activates 5-HT(1b) receptors resulting in a long-term depression (LTD) of glutamate release and striatal output that we have termed 5-HT-LTD. 5-HT-LTD is presynaptically mediated, cAMP pathway dependent, and inducible by endogenous striatal 5-HT, as revealed by application of a selective 5-HT reuptake inhibitor. 5-HT-LTD is mutually occlusive with dopamine/endocannabinoid-dependent LTD, suggesting that these two forms of LTD act on the same corticostriatal terminals. Thus, serotonergic and dopaminergic mechanisms exist that may interact to persistently sculpt corticostriatal circuits, potentially influencing action learning and striatal-based disorders.

  12. Long Term 1 Enhanced Surface Water Treatment Rule Documents

    EPA Pesticide Factsheets

    The Long Term 1 Enhanced Surface Water Treatment Rule (LT1ESWTR) builds on the requirements of the Surface Water Treatment Rule and specifies treatment requirements to address Cryptosporidium m and other microbial contaminants in public water systems.

  13. Mice Overexpressing Type 1 Adenylyl Cyclase Show Enhanced Spatial Memory Flexibility in the Absence of Intact Synaptic Long-Term Depression

    ERIC Educational Resources Information Center

    Zhang, Ming; Wang, Hongbing

    2013-01-01

    There is significant interest in understanding the contribution of intracellular signaling and synaptic substrates to memory flexibility, which involves new learning and suppression of obsolete memory. Here, we report that enhancement of Ca[superscript 2+]-stimulated cAMP signaling by overexpressing type 1 adenylyl cyclase (AC1) facilitated…

  14. Breast reconstruction after mastectomy: does it decrease depression at the long-term?

    PubMed Central

    Derks, Eveline Anne-Jet; Torensma, Bart; Honig, Adriaan; Vrouenraets, Bartholomeus Cornelius

    2016-01-01

    Background Depression is associated with breast cancer survivors in 22%. Although breast reconstruction (BR) is intended to provide psychological improvements such as reducing depression, literature is inconclusive and without long-term follow-up. The objective is to evaluate the impact of BR after breast cancer related mastectomy on the long-term depression risk and assess predictive factors for depression. Methods Women who underwent a curative mastectomy between 1999 and 2009 were included. After a mean follow-up of more than 6 years after operation, the Beck Depression Inventory-13 (BDI-13) evaluated depressive symptoms. Multivariable regression analysis provided predictors for depression. Results A total of 139 patients, 34 (24.5%) with and 105 (75.5%) without BR, were analyzed. Seventy-seven patients (48.2%) were at high risk for mild (n=58), moderate (n=5) or severe (n=4) depression. There was a trend for slightly better BDI-13 outcomes for women who underwent BR (2 vs. 4; P=0.06). Living alone [odds ratio (OR): 2.16; P=0.04], low educational level (OR: 3.70; P<0.01) and adjuvant hormonal/endocrine-therapy (OR: 2.36; P=0.02) were associated with an increased depression risk. Conclusions BR has no clear influence on depressive symptoms on the long-term. Predictive factors should alert clinicians to assess depressive symptoms in specific breast cancer patients during follow-up. PMID:27563558

  15. Major depressive disorder subtypes to predict long-term course

    PubMed Central

    van Loo, Hanna M.; Cai, Tianxi; Gruber, Michael J.; Li, Junlong; de Jonge, Peter; Petukhova, Maria; Rose, Sherri; Sampson, Nancy A.; Schoevers, Robert A.; Wardenaar, Klaas J.; Wilcox, Marsha A.; Al-Hamzawi, Ali Obaid; Andrade, Laura Helena; Bromet, Evelyn J.; Bunting, Brendan; Fayyad, John; Florescu, Silvia E.; Gureje, Oye; Hu, Chiyi; Huang, Yueqin; Levinson, Daphna; Medina-Mora, Maria Elena; Nakane, Yoshibumi; Posada-Villa, Jose; Scott, Kate M.; Xavier, Miguel; Zarkov, Zahari; Kessler, Ronald C.

    2016-01-01

    Background Variation in course of major depressive disorder (MDD) is not strongly predicted by existing subtype distinctions. A new subtyping approach is considered here. Methods Two data mining techniques, ensemble recursive partitioning and Lasso generalized linear models (GLMs) followed by k-means cluster analysis, are used to search for subtypes based on index episode symptoms predicting subsequent MDD course in the World Mental Health (WMH) Surveys. The WMH surveys are community surveys in 16 countries. Lifetime DSM-IV MDD was reported by 8,261 respondents. Retrospectively reported outcomes included measures of persistence (number of years with an episode; number of with an episode lasting most of the year) and severity (hospitalization for MDD; disability due to MDD). Results Recursive partitioning found significant clusters defined by the conjunctions of early onset, suicidality, and anxiety (irritability, panic, nervousness-worry-anxiety) during the index episode. GLMs found additional associations involving a number of individual symptoms. Predicted values of the four outcomes were strongly correlated. Cluster analysis of these predicted values found three clusters having consistently high, intermediate, or low predicted scores across all outcomes. The high-risk cluster (30.0% of respondents) accounted for 52.9-69.7% of high persistence and severity and was most strongly predicted by index episode severe dysphoria, suicidality, anxiety, and early onset. A total symptom count, in comparison, was not a significant predictor. Conclusions Despite being based on retrospective reports, results suggest that useful MDD subtyping distinctions can be made using data mining methods. Further studies are needed to test and expand these results with prospective data. PMID:24425049

  16. Nuclear Translocation of Jacob in Hippocampal Neurons after Stimuli Inducing Long-Term Potentiation but Not Long-Term Depression

    PubMed Central

    Behnisch, Thomas; YuanXiang, PingAn; Bethge, Philipp; Parvez, Suhel; Chen, Ying; Yu, Jin; Karpova, Anna; Frey, Julietta U.; Mikhaylova, Marina; Kreutz, Michael R.

    2011-01-01

    Background In recent years a number of potential synapto-nuclear protein messengers have been characterized that are thought to be involved in plasticity-related gene expression, and that have the capacity of importin- mediated and activity-dependent nuclear import. However, there is a surprising paucity of data showing the nuclear import of such proteins in cellular models of learning and memory. Only recently it was found that the transcription factor cyclic AMP response element binding protein 2 (CREB2) transits to the nucleus during long-term depression (LTD), but not during long-term potentiation (LTP) of synaptic transmission in hippocampal primary neurons. Jacob is another messenger that couples NMDA-receptor-activity to nuclear gene expression. We therefore aimed to study whether Jacob accumulates in the nucleus in physiological relevant models of activity-dependent synaptic plasticity. Methodology/Principal Findings We have analyzed the dynamics of Jacob's nuclear import following induction of NMDA-receptor dependent LTP or LTD at Schaffer collateral-CA1 synapses in rat hippocampal slices. Using time-lapse imaging of neurons expressing a Jacob-Green-Fluorescent-Protein we found that Jacob rapidly translocates from dendrites to the nucleus already during the tetanization period of LTP, but not after induction of LTD. Immunocytochemical stainings confirmed the nuclear accumulation of endogenous Jacob in comparison to apical dendrites after induction of LTP but not LTD. Complementary findings were obtained after induction of NMDA-receptor dependent chemical LTP and LTD in hippocampal primary neurons. However, in accordance with previous studies, high concentrations of NMDA and glycine as well as specific activation of extrasynaptic NMDA-receptors resembling pathological conditions induce an even more profound increase of nuclear Jacob levels. Conclusions/Significance Taken together, these findings suggest that the two major forms of NMDA-receptor dependent

  17. Erythropoietin enhances hippocampal long-term potentiation and memory

    PubMed Central

    Adamcio, Bartosz; Sargin, Derya; Stradomska, Alicja; Medrihan, Lucian; Gertler, Christoph; Theis, Fabian; Zhang, Mingyue; Müller, Michael; Hassouna, Imam; Hannke, Kathrin; Sperling, Swetlana; Radyushkin, Konstantin; El-Kordi, Ahmed; Schulze, Lizzy; Ronnenberg, Anja; Wolf, Fred; Brose, Nils; Rhee, Jeong-Seop; Zhang, Weiqi; Ehrenreich, Hannelore

    2008-01-01

    Background Erythropoietin (EPO) improves cognition of human subjects in the clinical setting by as yet unknown mechanisms. We developed a mouse model of robust cognitive improvement by EPO to obtain the first clues of how EPO influences cognition, and how it may act on hippocampal neurons to modulate plasticity. Results We show here that a 3-week treatment of young mice with EPO enhances long-term potentiation (LTP), a cellular correlate of learning processes in the CA1 region of the hippocampus. This treatment concomitantly alters short-term synaptic plasticity and synaptic transmission, shifting the balance of excitatory and inhibitory activity. These effects are accompanied by an improvement of hippocampus dependent memory, persisting for 3 weeks after termination of EPO injections, and are independent of changes in hematocrit. Networks of EPO-treated primary hippocampal neurons develop lower overall spiking activity but enhanced bursting in discrete neuronal assemblies. At the level of developing single neurons, EPO treatment reduces the typical increase in excitatory synaptic transmission without changing the number of synaptic boutons, consistent with prolonged functional silencing of synapses. Conclusion We conclude that EPO improves hippocampus dependent memory by modulating plasticity, synaptic connectivity and activity of memory-related neuronal networks. These mechanisms of action of EPO have to be further exploited for treating neuropsychiatric diseases. PMID:18782446

  18. Synaptic Function of Rab11Fip5: Selective Requirement for Hippocampal Long-Term Depression

    PubMed Central

    Ahmad, Mohiuddin; Jurado, Sandra; Malenka, Robert C.

    2015-01-01

    Postsynaptic AMPA-type glutamate receptors (AMPARs) are among the major determinants of synaptic strength and can be trafficked into and out of synapses. Neuronal activity regulates AMPAR trafficking during synaptic plasticity to induce long-term changes in synaptic strength, including long-term potentiation (LTP) and long-term depression (LTD). Rab family GTPases regulate most membrane trafficking in eukaryotic cells; particularly, Rab11 and its effectors are implicated in mediating postsynaptic AMPAR insertion during LTP. To explore the synaptic function of Rab11Fip5, a neuronal Rab11 effector and a candidate autism-spectrum disorder gene, we performed shRNA-mediated knock-down and genetic knock-out (KO) studies. Surprisingly, we observed robust shRNA-induced synaptic phenotypes that were rescued by a Rab11Fip5 cDNA but that were nevertheless not observed in conditional KO neurons. Both in cultured neurons and acute slices, KO of Rab11Fip5 had no significant effect on basic parameters of synaptic transmission, indicating that Rab11Fip5 is not required for fundamental synaptic operations, such as neurotransmitter release or postsynaptic AMPAR insertion. KO of Rab11Fip5 did, however, abolish hippocampal LTD as measured both in acute slices or using a chemical LTD protocol in cultured neurons but did not affect hippocampal LTP. The Rab11Fip5 KO mice performed normally in several behavioral tasks, including fear conditioning, but showed enhanced contextual fear extinction. These are the first findings to suggest a requirement for Rab11Fip5, and presumably Rab11, during LTD. PMID:25972173

  19. 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

    2016-05-03

    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.

  20. Notation of Depression in Case Records of Older Adults in Community Long-Term Care

    ERIC Educational Resources Information Center

    Proctor, Enola K.

    2008-01-01

    Although significant numbers of social service clients experience mental health problems, virtually no research has examined the responsiveness of social service agencies to mental disorder. This article examines the extent to which client depression is reflected in records of a public social service agency, community long-term care (CLTC).…

  1. Long-Term Effects of a Home-Visiting Intervention for Depressed Mothers and Their Infants

    ERIC Educational Resources Information Center

    Kersten-Alvarez, Laura E.; Hosman, Clemens M. H.; Riksen-Walraven, J. Marianne; Van Doesum, Karin T. M.; Hoefnagels, Cees

    2010-01-01

    Background: Whereas preventive interventions for depressed mothers and their infants have yielded positive short-term outcomes, few studies have examined their long-term effectiveness. The present follow-up of a randomised controlled trial (RCT) is one of the first to examine the longer-term effects of an intervention for mothers with postpartum…

  2. Observer-rated depression in long-term care: frequency and risk factors.

    PubMed

    McCusker, Jane; Cole, Martin G; Voyer, Philippe; Monette, Johanne; Champoux, Nathalie; Ciampi, Antonio; Vu, Minh; Dyachenko, Alina; Belzile, Eric

    2014-01-01

    The objectives of this study were: (1) to describe the prevalence and 6-month incidence of observer-rated depression in residents age 65 and over of long-term care (LTC) facilities; (2) to describe risk factors for depression, at baseline and over time. A multisite, prospective observational study was conducted in residents aged 65 and over of 7 LTC facilities. The Cornell Scale for Depression in Dementia (CSDD) was completed by nurses monthly for 6 months. We measured demographic, medical, and functional factors at baseline and monthly intervals, using data from research assessments, nurse interviews, and chart reviews. 274 residents were recruited and completed baseline depression assessments. The prevalence of depression (CSDD score of 6+) was 19.0%. The incidence of depression among those without prevalent depression was 73.3 per 100 person-years. A delirium diagnosis, pain, and diabetes were independently associated with prevalent depression. CSDD score at baseline and development of severe cognitive impairment at follow-up were independent risk factors for incident depression. A diagnosis of delirium and uncorrected visual impairment at follow-up occurred concurrently with incident depression. The results of this study have implications for the detection and prevention of depression in LTC. Delirium diagnosis, pain and diabetes at baseline were associated with prevalent depression; depression symptoms at baseline and development of severe cognitive impairment at follow-up were risk factors for incident depression.

  3. 24-hour-restraint stress induces long-term depressive-like phenotypes in mice

    PubMed Central

    Zhou, Ying; Hu, Zhiqiang; Lou, Jingyu; Song, Wei; Li, Jing; Liang, Xiao; Chen, Chen; Wang, Shuai; Yang, Beimeng; Chen, Lei; Zhang, Xu; Song, Jinjing; Dong, Yujie; Chen, Shiqing; He, Lin; Xie, Qingguo; Chen, Xiaoping; Li, Weidong

    2016-01-01

    There is an increasing risk of mental disorders, such as acute stress disorder (ASD), post-traumatic stress disorder (PTSD) and depression among survivors who were trapped in rubble during earthquake. Such long-term impaction of a single acute restraint stress has not been extensively explored. In this study, we subjected mice to 24-hour-restraint to simulate the trapping episode, and investigated the acute (2 days after the restraint) and long-term (35 days after the restraint) impacts. Surprisingly, we found that the mice displayed depression-like behaviors, decreased glucose uptake in brain and reduced adult hippocampal neurogenesis 35 days after the restraint. Differential expression profiling based on microarrays suggested that genes and pathways related to depression and other mental disorders were differentially expressed in both PFC and hippocampus. Furthermore, the depression-like phenotypes induced by 24-hour-restraint could be reversed by fluoxetine, a type of antidepressant drug. These findings demonstrated that a single severe stressful event could produce long-term depressive-like phenotypes. Moreover, the 24-hour-restraint stress mice could also be used for further studies on mood disorders. PMID:27609090

  4. [The long-term course of depression and dementia in the aged].

    PubMed

    Oesterreich, K

    1989-01-01

    Results of measurements of geropsychiatric syndromes are different. The statements are based on application of various methods and investigations of non-comparable populations. Nevertheless it is possible to draw the following conclusions out of the scientific papers and experiences of our own: A chronicity of depressive long-term courses is expected on old and higher age. Somatic diseases and organic brain syndrome render more difficult the amelioration and pharmacotherapy. The symptoms of affective disorders in old age most differ from depression in early and adult biographic phase. The course of dementias take off age and attendant somatic illness. In old age increase dementias. Their prognosis is worse. Added somatic process affects the further course negatively and renders more difficult the therapy. Long-term courses of dementias in old and higher age complicate the precise differential-diagnostic attach on pathogenetics. Social influences take effect on the course of depression and dementia advantageously or disadvantageously.

  5. Adapting Collaborative Depression Care for Public Community Long-Term Care: Using Research-Practice Partnerships

    PubMed Central

    Lenze, Shannon; Brown, Teresa; Lawrence, Lisa; Nickel, Mike; Morrow-Howell, Nancy; Proctor, Enola K.

    2014-01-01

    Description This manuscript details potential benefits for using a research-practice partnership to adapt collaborative depression care for public community long-term care agencies serving older adults. We used sequential, multi-phase, and mixed methods approaches for documenting the process of adaptation within a case study. Systematic adaptation strategies are described, such as leveraging long-term research-practice collaborations, consulting with multiple stakeholders across all levels and disciplines, and balancing demands to monitor treatment fidelity, clinical outcomes, and implementation results. These examples demonstrate that researchers interested in implementation science need skills to negotiate the competing demands that arise from both the research and practice settings. PMID:24072560

  6. Adapting collaborative depression care for public community long-term care: using research-practice partnerships.

    PubMed

    Hasche, Leslie K; Lenze, Shannon; Brown, Teresa; Lawrence, Lisa; Nickel, Mike; Morrow-Howell, Nancy; Proctor, Enola K

    2014-09-01

    This manuscript details potential benefits for using a research-practice partnership to adapt collaborative depression care for public community long-term care agencies serving older adults. We used sequential, multi-phase, and mixed methods approaches for documenting the process of adaptation within a case study. Systematic adaptation strategies are described, such as leveraging long-term research-practice collaborations, consulting with multiple stakeholders across all levels and disciplines, and balancing demands to monitor treatment fidelity, clinical outcomes, and implementation results. These examples demonstrate that researchers interested in implementation science need skills to negotiate the competing demands that arise from both the research and practice settings.

  7. 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

  8. Long-term depression in vivo: effects of sex, stress, diet, and prenatal ethanol exposure.

    PubMed

    Titterness, Andrea K; Christie, Brian R

    2008-01-01

    Long-term depression (LTD) of synaptic efficacy has proven a difficult phenomenon to examine in vivo, despite the ease with which it is induced in a variety of in vitro preparations. Prior exposure to an acute stressful episode does however seem to enhance the capacity of the hippocampus to exhibit LTD in vivo in male animals. In the present experiments, we examined the capacity for low-frequency stimuli (low-frequency stimulation (LFS)) to induce LTD in juvenile male and female animals following an acute stress episode. Interestingly, prior exposure to stress was only required for the induction of LTD in male animals, while both control and stressed female animals exhibited equivalent LTD. In animals that were exposed to ethanol in utero, a similar requirement for prior exposure to stress to elicit LTD was found for male, but not female animals. This prenatal ethanol exposure did not in itself alter the capacity for LTD induction in either sex; however, in utero food restriction did enhance LTD induction in both male and female animals, irrespective of whether they were exposed to stress just prior to being administered LFS. These results indicate that in utero dietary restriction more drastically affects CA1 LTD than in utero ethanol exposure. In addition, female animals seem to exhibit LTD in vivo in the absence of stress much more easily than their male counterparts.

  9. Long-term association between seizure outcome and depression after resective epilepsy surgery

    PubMed Central

    Liu, H.; Cong, X.; Devinsky, O.; Berg, A.T.; Vickrey, B.G.; Sperling, M.R.; Shinnar, S.; Langfitt, J.T.; Walczak, T.S.; Barr, W.B.; Dziura, J.; Bazil, C.W.; Spencer, S.S.

    2011-01-01

    Objective: This study explored the association between long-term epilepsy surgery outcome and changes in depressive symptoms. Methods: Adults were enrolled between 1996 and 2001 in a multicenter prospective study to evaluate outcomes of resective epilepsy surgery. The extent of depressive symptoms and depression case status (none, mild, or moderate/severe) were assessed using the Beck Depression Inventory (BDI) preoperatively and 3, 12, 24, 48, and 60 months postoperatively. A mixed-model repeated-measures analysis was performed, adjusting for covariates of seizure location, gender, age, race, education, and seizure control. Results: Of the total 373 subjects, 256 were evaluated at baseline and 5 years after surgery. At baseline, 164 (64.1%) were not depressed, 34 (13.3%) were mildly depressed, and 58 (22.7%) had moderate to severe depression. After 5 years, 198 (77.3%) were not depressed, 20 (7.8%) were mildly depressed, and 38 (14.8%) were moderately to severely depressed. Five years after surgery, the reduction in mean change from baseline in BDI score was greater in subjects with excellent seizure control than in the fair and poor seizure control groups (p = 0.0006 and p = 0.02 respectively). Those with good seizure control had a greater reduction in BDI score than the poor seizure control group (p = 0.02) and borderline significant reduction compared with the fair seizure control group (p = 0.055). Conclusion: Although study participants had initial improvement in depressive symptoms, on average, after resective surgery, only patients with good or excellent seizure control had sustained long-term improvement in mood. PMID:22094480

  10. 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.

  11. A calcineurin/AKAP complex is required for NMDA receptor-dependent long-term depression.

    PubMed

    Jurado, Sandra; Biou, Virginie; Malenka, Robert C

    2010-09-01

    AKAP79/150 is a protein scaffold that is thought to position specific kinases (protein kinase A and C) and phosphatases (calcineurin) in appropriate synaptic domains so that their activities can regulate excitatory synaptic strength. Using a viral-mediated molecular replacement strategy in rat hippocampal slices, we found that AKAP is required for NMDA receptor-dependent long-term depression solely because of its interaction with calcineurin.

  12. Enhanced Polyhydroxybutyrate Production for Long-Term Spaceflight Applications

    NASA Technical Reports Server (NTRS)

    Putman, Ryan J.; Rahman, Asif; Miller, Charles D.; Hadi, Masood Z.

    2015-01-01

    Synthetic biology holds the promise of advancing long term space fight by the production of medicine, food, materials, and energy. One such application of synthetic biology is the production of biomaterials, specifically polyhydroxyalkanoates (PHAs), using purposed organisms such as Escherichia coli. PHAs are a group of biodegradable bioplastics that are produced by a wide variety of naturally occurring microorganisms, mainly as an energy storage intermediate. PHAs have similar melting point to polypropylene and a Youngs modulus close to polystyrene. Due to limited resources and cost of transportation, large-scale extraction of biologically produced products in situ is extremely cumbersome during space flight. To that end, we are developing a secretion systems for exporting PHA from the cell in order to reduce unit operations. PHAs granules deposited inside bacteria are typically associated with proteins bound to the granule surface. Phasin, a granule bound protein, was targeted for type I secretion by fusion with HlyA signal peptide for indirect secretion of PHAs. In order to validate our secretion strategy, a green fluorescent protein (GFP) was tagged to the PHA polymerase enzyme (phaC), this three part gene cassette consists of phaA and phaB and are required for PHA production. Producing PHAs in situ during space flight or planet colonization will enable mission success by providing a valuable source of biomaterials that can have many potential applications thereby reducing resupply requirements. Biologically produced PHAs can be used in additive manufacturing such as three dimensional (3D) printing to create products that can be made on demand during space flight. After exceeding their lifetime, the PHAs could be melted and recycled back to 3D print other products. We will discuss some of our long term goals of this approach.

  13. Long term efficacy of paroxetine in major depression: A study with plasma levels.

    PubMed

    Mauri, M C; Laini, V; Bitetto, A; Boscati, L; Scalvini, M; Mapelli, L; Rudelli, R

    1999-01-01

    Depressive disorders can be regarded as recurrent and chronic conditions that may reduce the quality of life and work output of patients. Data on the long-term efficacy of paroxetine appear to indicate that it is an effective maintenance treatment. Our aim was to measure paroxetine concentrations in plasma in order to optimize its clinical efficacy and tolerability during long-term treatment. We studied 35 patients aged 23-70 years, suffering from Major Depressive Disorder (recurrent). These patients received 10-50 mg of paroxetine once a day for one year; they were evaluated at baseline, after 2 weeks and then after 1,2,6,9 and 12 months by BPRS, HRS-D and HRS-A rating scales, and at the same time, any side-effects were assessed and samples for paroxetine plasma determination were also collected. Results confirmed the efficacy and tolerability of paroxetine for long-term treatment. We observed a curvilinear relationship between plasma paroxetine levels and improvement on the HRS-D with greater clinical amelioration at plasma levels between 20 and 70 ng/ml.

  14. Ubiquitin-Proteasome System Inhibition Promotes Long-Term Depression and Synaptic Tagging/Capture.

    PubMed

    Li, Qin; Korte, Martin; Sajikumar, Sreedharan

    2016-06-01

    A balance of protein synthesis and degradation is critical for the dynamic regulation and implementation of long-term memory storage. The role of the ubiquitin-proteasome system (UPS) in regulating the plasticity at potentiated synapses is well studied, but its roles in depressed synaptic populations remain elusive. In this study, we probed the possibility of regulating the UPS by inhibiting the proteasome function during the induction of protein synthesis-independent form of hippocampal long-term depression (early-LTD), an important component of synaptic plasticity. Here, we show that protein degradation is involved in early-LTD induction and interfering with this process facilitates early-LTD to late-LTD. We provide evidence here that under the circumstances of proteasome inhibition brain-derived neurotrophic factor is accumulated as plasticity-related protein and it drives the weakly depressed or potentiated synapses to associativity. Thus, UPS inhibition promotes LTD and establishes associativity between weakly depressed or potentiated synapses through the mechanisms of synaptic tagging/capture or cross-capture.

  15. Does long-term experience of nonstandard employment increase the incidence of depression in the elderly?

    PubMed Central

    Kang, Mo-Yeol; Kang, Young-Joong; Lee, Woncheol; Yoon, Jin-Ha

    2016-01-01

    Objectives: Our prospective study aimed to elucidate the effect of long-term experience of nonstandard employment status on the incidence of depression in elderly population using the Korean Longitudinal Study of Ageing (KLoSA) study. Methods: This study used the first- to fourth-wave cohorts of KLoSA. After the exclusion of the unemployed and participants who experienced a change in employment status during the follow-up periods, we analyzed a total of 1,817 participants. Employment contracts were assessed by self-reported questions:standard or nonstandard employment. The short form of the Center for Epidemiologic Studies Depression Scale (CES-D) served as the outcome measure. Hazard ratios (HRs) with 95% confidence intervals (CIs) were calculated using Cox proportional hazards models to evaluate the association between standard/nonstandard employees and development of depression. Results: The mean age of the participants was 53.90 (±7.21) years. We observed that nonstandard employment significantly increased the risk of depression. Compared with standard employees, nonstandard employees had a 1.5-fold elevated risk for depression after adjusting for age, gender, CES-D score at baseline, household income, occupation category, current marital status, number of living siblings, perceived health status, and chronic diseases [HR=1.461, 95% CI= (1.184, 1.805) ]. Moreover, regardless of other individual characteristics, the elevated risk of depression was observed among all kinds of nonstandard workers, such as temporary and day workers, full-time and part-time workers, and directly employed and dispatched labor. Conclusions: The 6-year follow-up study revealed that long-term experience of nonstandard employment status increased the risk of depression in elderly population in Korea. PMID:27108642

  16. Depression, anxiety and quality of life in caregivers of long-term home care patients.

    PubMed

    Yıkılkan, Hülya; Aypak, Cenk; Görpelioğlu, Süleyman

    2014-06-01

    Family caregivers of patient in long-term care facilities often have high rates of stress, burden and psychological illness. A descriptive study was carried out with 63 caregivers. Caregivers were asked to complete a demographic questionnaire, Beck Depression Inventory (BDI), Beck Anxiety Inventory (BAI) and Short form 36 (SF-36), which measures health related quality of life (QoL). The majority of caregivers were female (79.4%), and most often the daughter of the patient in long-term care (47.6%). The mean BDI score of the sample was 18.8, and the mean BAI score was 20.0. Almost all the mean scores referring to the QoL were decreased (lower than 50), with the exception of mental health. On the SF-36 questionnaire, the lowest scores were observed on the role-emotional, role-physical, social functioning and vitality scales of the SF-36.

  17. Calcium as a trigger for cerebellar long-term synaptic depression.

    PubMed

    Finch, Elizabeth A; Tanaka, Keiko; Augustine, George J

    2012-09-01

    Cerebellar long-term depression (LTD) is a form of long-term synaptic plasticity that is triggered by calcium(Ca2+) signals in the postsynaptic Purkinje cell. This Ca2+comes both from IP3-mediated release from intracellular Ca2+ stores, as well as from Ca2+ influx through voltage-gated Ca2+ channels. The Ca2+ signal that triggers LTD occurs locally within dendritic spines and is due to supralinear summation of signals coming from these two Ca2+ sources. The properties of this postsynaptic Ca2+signal can explain several features of LTD, such as its associativity, synapse specificity, and dependence on thetiming of synaptic activity, and can account for the slow kinetics of LTD expression. Thus, from a Ca2+ signaling perspective, LTD is one of the best understood forms of synaptic plasticity.

  18. Pets, depression and long term survival in community living patients following myocardial infarction

    PubMed Central

    Friedmann, Erika; Thomas, Sue A.; Son, Heesook

    2011-01-01

    Evidence supports the contribution of depression, anxiety, and poor social support to mortality of hospitalized myocardial infarction (MI) patients. The contribution of depression to survival is independent of disease severity. Pet ownership, a non-human form of social support, has also been associated with one year survival of post-MI patients. The current study addresses whether pet ownership contributes independently to long term survival beyond the contributions of depression, anxiety, or low social support in post-MI patients who have already survived at least 6 months. Data from patients (N = 460) enrolled in the “Psychosocial Responses in the Home Automated External Defibrillator Trial (PR-HAT)”were used. Seventeen patients died during a median follow-up of 2.8 years. In Cox proportional hazards regression model that included depression, lack of pet ownership, and the interaction between depression and lack of pet ownership, not owning a pet was the only significant independent predictor of mortality (p = 0.036). The interaction between pet ownership and depression tended to be significant indicating that the effect of pet ownership on survival in this group of people who have supportive spouses/companions living with them may relate to depression. PMID:21857770

  19. Heterogeneity in long-term trajectories of depressive symptoms: Patterns, predictors and outcomes

    PubMed Central

    Musliner, Katherine L.; Munk-Olsen, Trine; Eaton, William W.; Zandi, Peter P.

    2016-01-01

    Background Evidence suggests that long-term trajectories of depressive symptoms vary greatly throughout the population, with some individuals experiencing few or no symptoms, some experiencing transient symptoms and others experiencing chronic depression. The goal of this paper was to review studies that examined heterogeneity in long-term trajectories of depressive symptoms and summarize the current knowledge regarding a) the number and patterns of trajectories and b) antecedents and outcomes associated with different trajectory patterns. Methods We conducted a systematic review of literature in the Medline and PsychINFO databases. Articles were included if they a) modeled trajectories of depressive symptoms, b) used a group-based trajectory modeling approach, c) followed participants for 5+ years and d) had a sample size of at least 200. Results We identified 25 studies from 24 separate cohorts. Most of the studies identified either 3 or 4 distinct trajectory classes. Trajectories varied in terms of severity (low, medium, high) and stability (stable, increasing, decreasing). In most studies, the majority of participants had consistently few or no depressive symptoms, but a notable minority (usually < 10%) reported persistent symptoms. Predictors of trajectories with greater symptom burden included female gender, lower income/education and non-white race. Other predictors were specific to different populations (i.e. mothers, older adults). High symptom burden trajectories were associated with poor psychiatric and psychosocial outcomes. Limitations Comparisons between studies were qualitative. Conclusions Trajectories of depression symptoms in the general population are heterogeneous, with most individuals showing minimal symptoms but a notable minority experiencing chronic high symptom burden. PMID:26745437

  20. Long term life dissatisfaction and subsequent major depressive disorder and poor mental health

    PubMed Central

    2011-01-01

    Background Poor mental health, especially due to depression, is one of the main public health problems. Early indicators of poor mental health in general population are needed. This study examined the relationship between long-term life dissatisfaction and subsequent mental health, including major depressive disorder. Method Health questionnaires were sent to a randomly selected population-based sample in 1998 and repeated in 1999 and 2001. In 2005, a clinically studied sub-sample (n = 330) was composed of subjects with (n = 161) or without (n = 169) repeatedly reported adverse mental symptoms at all three previous data collection times. Clinical symptom assessments were performed with several psychometric scales: life satisfaction (LS), depression (HDRS, BDI), hopelessness (HS), mental distress (GHQ), dissociative experiences (DES), and alexithymia (TAS). The long-term life dissatisfaction burden was calculated by summing these life satisfaction scores in 1998, 1999, 2001 and dividing the sum into tertiles. Psychiatric diagnoses were confirmed by SCID-I for DSM-IV in 2005. Logistic regression analyses were performed to assess the studied relationship. Results The previous life dissatisfaction burden associated with adverse socio-demographic, life style and clinical factors. In adjusted logistic regression analyses, it was independently and strongly associated with subsequent major depressive disorder in 2005, even when the concurrent LS score in 2005 was included in the model. Excluding those with reported major depressive disorder in 1999 did not alter this finding. Limitations MDD in 1999 was based on self-reports and not on structured interview and LS data in 2001-2005 was not available. Conclusions The life satisfaction burden is significantly related to major depressive disorder and poor mental health, both in cross-sectional and longitudinal settings. PMID:21861908

  1. Long-term elevated atmospheric CO2 enhances forest productivity

    NASA Astrophysics Data System (ADS)

    Loecke, T. D.; Groffman, P. M.; Treseder, K. K.; LaDeau, S.

    2011-12-01

    Global atmospheric CO2 concentrations are increasing at historically unprecedented but ecologically gradual rates. The implications of this perturbation for carbon sequestration and feedback on global climate change are difficult to predict due in part to its gradual and largely uniform nature. We used long-term (>40 years) spatial gradients in atmospheric CO2 concentration, produced by spatially heterogeneous fossil fuel combustion along a rural to urban transect, to test the hypotheses that 1) rural to urban CO2 spatial gradients are useful analogs for gradual climate change and 2) higher atmospheric CO2 concentration promotes tree growth and C sequestration. Fossil fuel derived CO2 imparts a distinctive 14C isotopic signature on atmospheric CO2; as this CO2 is fixed into annual tree rings, a proxy for fossil fuel derived CO2 is preserved. Ten four-year tree ring segments were analyzed for α-cellulose 14C content by AMS from trees within 10 closed canopy forested sites in the Baltimore Maryland metropolitan area. Tree growth parameters were assessed by measuring the annual ring width change of 224 trees across the 10 sites. A hierarchical Bayesian model was constructed to determine the influence of CO2 concentration and other site and environmental factors on tree growth. Our proxy for historical CO2 concentrations indicates a detectable but diminishing spatial CO2 gradient across the rural to urban transect that ranged from a 5.6% gradient during the 1970s to a 1.4% gradient in recent years (2000-2008). This observation is consistent with urban deindustrialization and concurrent expansion of suburban development. As an analog for future atmospheric conditions, this spatial gradient is equivalent to a temporal gradient of ca. 15, 7.2, 9.8, 2.6 years of atmospheric CO2 rise during the past four decades. The CO2 spatial gradient had an overall positive effect on tree size adjusted ring width growth. Modeled air surface temperature differences among sites indicate

  2. Long-term depression triggers the selective elimination of weakly integrated synapses.

    PubMed

    Wiegert, J Simon; Oertner, Thomas G

    2013-11-19

    Long-term depression (LTD) weakens synaptic transmission in an activity-dependent manner. It is not clear, however, whether individual synapses are able to maintain a depressed state indefinitely, as intracellular recordings rarely exceed 1 h. Here, we combine optogenetic stimulation of identified Schaffer collateral axons with two-photon imaging of postsynaptic calcium signals and follow the fate of individual synapses for 7 d after LTD induction. Optogenetic stimulation of CA3 pyramidal cells at 1 Hz led to strong and reliable depression of postsynaptic calcium transients in CA1. NMDA receptor activation was necessary for successful induction of LTD. We found that, in the days following LTD, many depressed synapses and their "neighbors" were eliminated from the hippocampal circuit. The average lifetime of synapses on nonstimulated dendritic branches of the same neurons remained unaffected. Persistence of individual depressed synapses was highly correlated with reliability of synaptic transmission, but not with spine size or the amplitude of spine calcium transients. Our data suggest that LTD initially leads to homogeneous depression of synaptic function, followed by selective removal of unreliable synapses and recovery of function in the persistent fraction.

  3. The Long-Term Effects of Maternal Depression: Early Childhood Physical Health as a Pathway to Offspring Depression

    PubMed Central

    Hammen, Constance; Brennan, Patricia; Najman, Jake

    2013-01-01

    Purpose Cross sectional and retrospective studies have highlighted the long-term negative effects of maternal depression on offspring physical, social, and emotional development, but longitudinal research is needed to clarify the pathways by which maternal depression during pregnancy and early childhood affects offspring outcomes. The current study tested one developmental pathway by which maternal depression during pregnancy might negatively impact offspring mental health in young adulthood, via poor physical health in early childhood. Methods The sample consisted of 815 Australian youth and their mothers who were followed for 20 years. Mothers reported on their own depressive symptoms during pregnancy and offspring early childhood. Youth completed interviews about health-related stress and social functioning at age 20, and completed a questionnaire about their own depressive symptoms two to five years later. Results Path analysis indicated that prenatal maternal depressive symptoms predicted worse physical health during early childhood for offspring, and this effect was partially explained by ongoing maternal depression in early childhood. Offspring poor physical health during childhood predicted increased health-related stress and poor social functioning at age 20. Finally, increased health-related stress and poor social functioning predicted increased levels of depressive symptoms later in young adulthood. Maternal depression had a significant total indirect effect on youth depression via early childhood health and its psychosocial consequences. Conclusions Poor physical health in early childhood and its effects on young adults’ social functioning and levels of health related stress are one important pathway by which maternal depression has long-term consequences for offspring mental health. PMID:24060574

  4. Purkinje cell stripes and long-term depression at the parallel fiber-Purkinje cell synapse

    PubMed Central

    Hawkes, Richard

    2014-01-01

    The cerebellar cortex comprises a stereotyped array of transverse zones and parasagittal stripes, built around multiple Purkinje cell subtypes, which is highly conserved across birds and mammals. This architecture is revealed in the restricted expression patterns of numerous molecules, in the terminal fields of the afferent projections, in the distribution of interneurons, and in the functional organization. This review provides an overview of cerebellar architecture with an emphasis on attempts to relate molecular architecture to the expression of long-term depression (LTD) at the parallel fiber-Purkinje cell (pf-PC) synapse. PMID:24734006

  5. Opioids induce dissociable forms of long-term depression of excitatory inputs to the dorsal striatum.

    PubMed

    Atwood, Brady K; Kupferschmidt, David A; Lovinger, David M

    2014-04-01

    As prescription opioid analgesic abuse rates rise, so does the need to understand the long-term effects of opioid exposure on brain function. The dorsal striatum is an important site for drug-induced neuronal plasticity. We found that exogenously applied and endogenously released opioids induced long-term depression (OP-LTD) of excitatory inputs to the dorsal striatum in mice and rats. Mu and delta OP-LTD, although both being presynaptically expressed, were dissociable in that they summated, differentially occluded endocannabinoid-LTD and inhibited different striatal inputs. Kappa OP-LTD showed a unique subregional expression in striatum. A single in vivo exposure to the opioid analgesic oxycodone disrupted mu OP-LTD and endocannabinoid-LTD, but not delta or kappa OP-LTD. These data reveal previously unknown opioid-mediated forms of long-term striatal plasticity that are differentially affected by opioid analgesic exposure and are likely important mediators of striatum-dependent learning and behavior.

  6. Diabetes mellitus- and ageing-induced changes in the capacity for long-term depression and long-term potentiation inductions: toward a unified mechanism.

    PubMed

    Artola, Alain

    2013-11-05

    Long-lasting type 1 and type 2 diabetes mellitus (DM) are both associated with impaired cognitive function in humans. Animal models of DM have confirmed the detrimental effect of high blood glucose levels on learning and memory. What are the neural correlates of such impaired cognition? It is widely, although not universally, believed that long-lasting increase and decrease in synaptic strength, known as long-term potentiation (LTP) and depression (LTD), provide an important key to understanding the cellular and molecular mechanisms by which memories are formed and stored. The majority of animal studies that examined the effect of DM on LTD and LTP used the streptozotocin (STZ) rodent model of type 1 DM, with the exception of a few that used genetic models of type 2 DM. Studies in STZ-DM rodents show that cellular processes underlying synapse strengthening or weakening are not altered. Rather, the capacity for LTP induction is reduced whereas that for LTD induction is enhanced. The mechanisms underlying DM-related changes in LTD and LTP inductions are still unknown. However, that the levels of effective postsynaptic depolarization for LTD and LTP inductions are concomitantly shifted in opposite directions put constraints on them. Moreover, that DM-, metaplasticity-, stress- and ageing-related changes in LTD and LTP inductions exhibit the very same phenomenology suggests that they might involve common mechanisms. Dissecting out the mechanisms responsible for DM-related changes in the capacity for LTD and LTP inductions is helping to improve treatment of impaired cognitive function in DM patients.

  7. 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

  8. [Anxiety and depressive disorders in 4,425 long term benzodiazepine users in general practice].

    PubMed

    Pélissolo, A; Maniere, F; Boutges, B; Allouche, M; Richard-Berthe, C; Corruble, E

    2007-01-01

    .5%). An anxiety and depressive comorbidity wad found in 41.9% of the subjects. Some methodological limitations must be taken into account in the discussion of our results, and especially the fact that the included patients were not supposed to be totally representative of all patients consuming anxiolytic benzodiazepines in general practice. However, the size of our sample is sufficiently large to limit possible biases in patient selection. The main result of this study is that a great majority of the patients had significant symptomatology, in particular major depressive episodes and generalized anxiety disorder, often with marked severity and disability. These data are in line with the knowledge of a lack of efficacy of benzodiazepines in depressive and most anxiety disorders, despite long term treatment. They also confirm the current guidelines which recommend prescribing serotoninergic antidepressants, and not benzodiazepines, when long term treatments are needed for severe and chronic affective disorders. This epidemiologic study leads to the conclusion that a specific and attentive diagnostic assessment should be done in all patients receiving benzodiazepines for more than three months, in order to purpose in many cases other long term therapeutic strategies.

  9. Two Loci of expression for long-term depression at hippocampal mossy fiber-interneuron synapses.

    PubMed

    Lei, Saobo; McBain, Chris J

    2004-03-03

    Two distinct forms of long-term depression (LTD) exist at mossy fiber synapses between dentate gyrus granule cells and hippocampal CA3 stratum lucidum interneurons. Although induction of each form of LTD requires an elevation of postsynaptic intracellular Ca2+, at Ca2+-impermeable AMPA receptor (CI-AMPAR) synapses, induction is NMDA receptor (NMDAR) dependent, whereas LTD at Ca2+-permeable AMPA receptor (CP-AMPAR) synapses is NMDAR independent. However, the expression locus of either form of LTD is not known. Using a number of criteria, including the coefficient of variation, paired-pulse ratio, AMPA-NMDA receptor activity, and the low-affinity AMPAR antagonist gamma-D-glutamyl-glycine, we demonstrate that LTD expression at CP-AMPAR synapses is presynaptic and results from reduced transmitter release, whereas LTD expression at CI-AMPAR synapses is postsynaptic. The N-ethylmaleimide-sensitive fusion protein-AP2-clathrin adaptor protein 2 inhibitory peptide pep2m occluded LTD expression at CI-AMPAR synapses but not at CP-AMPAR synapses, confirming that CI-AMPAR LTD involves postsynaptic AMPAR trafficking. Thus, mossy fiber innervation of CA3 stratum lucidum interneurons occurs via two parallel systems targeted to either Ca2+-permeable or Ca2+-impermeable AMPA receptors, each with a distinct expression locus for long-term synaptic plasticity.

  10. Metabotropic glutamate receptor-mediated long-term depression: molecular mechanisms.

    PubMed

    Gladding, Clare M; Fitzjohn, Stephen M; Molnár, Elek

    2009-12-01

    The ability to modify synaptic transmission between neurons is a fundamental process of the nervous system that is involved in development, learning, and disease. Thus, synaptic plasticity is the ability to bidirectionally modify transmission, where long-term potentiation and long-term depression (LTD) represent the best characterized forms of plasticity. In the hippocampus, two main forms of LTD coexist that are mediated by activation of either N-methyl-d-aspartic acid receptors (NMDARs) or metabotropic glutamate receptors (mGluRs). Compared with NMDAR-LTD, mGluR-LTD is less well understood, but recent advances have started to delineate the underlying mechanisms. mGluR-LTD at CA3:CA1 synapses in the hippocampus can be induced either by synaptic stimulation or by bath application of the group I selective agonist (R,S)-3,5-dihydroxyphenylglycine. Multiple signaling mechanisms have been implicated in mGluR-LTD, illustrating the complexity of this form of plasticity. This review provides an overview of recent studies investigating the molecular mechanisms underlying hippocampal mGluR-LTD. It highlights the role of key molecular components and signaling pathways that are involved in the induction and expression of mGluR-LTD and considers how the different signaling pathways may work together to elicit a persistent reduction in synaptic transmission.

  11. Multiple receptors coupled to phospholipase C gate long-term depression in visual cortex.

    PubMed

    Choi, Se-Young; Chang, Jeff; Jiang, Bin; Seol, Geun-Hee; Min, Sun-Seek; Han, Jung-Soo; Shin, Hee-Sup; Gallagher, Michela; Kirkwood, Alfredo

    2005-12-07

    Long-term depression (LTD) in sensory cortices depends on the activation of NMDA receptors. Here, we report that in visual cortical slices, the induction of LTD (but not long-term potentiation) also requires the activation of receptors coupled to the phospholipase C (PLC) pathway. Using immunolesions in combination with agonists and antagonists, we selectively manipulated the activation of alpha1 adrenergic, M1 muscarinic, and mGluR5 glutamatergic receptors. Inactivation of these PLC-coupled receptors prevents the induction of LTD, but only when the three receptors were inactivated together. LTD is fully restored by activating any one of them or by supplying intracellular D-myo-inositol-1,4,5-triphosphate (IP3). LTD was also impaired by intracellular application of PLC or IP3 receptor blockers, and it was absent in mice lacking PLCbeta1, the predominant PLC isoform in the forebrain. We propose that visual cortical LTD requires a minimum of PLC activity that can be supplied independently by at least three neurotransmitter systems. This essential requirement places PLC-linked receptors in a unique position to control the induction of LTD and provides a mechanism for gating visual cortical plasticity via extra-retinal inputs in the intact organism.

  12. Metabotropic glutamate receptor dependent long-term depression in the cortex

    PubMed Central

    Kang, Sukjae Joshua

    2016-01-01

    Metabotropic glutamate receptor (mGluR)-dependent long-term depression (LTD), a type of synaptic plasticity, is characterized by a reduction in the synaptic response, mainly at the excitatory synapses of the neurons. The hippocampus and the cerebellum have been the most extensively studied regions in mGluR-dependent LTD, and Group 1 mGluR has been reported to be mainly involved in this synaptic LTD at excitatory synapses. However, mGluR-dependent LTD in other brain regions may be involved in the specific behaviors or diseases. In this paper, we focus on five cortical regions and review the literature that implicates their contribution to the pathogenesis of several behaviors and specific conditions associated with mGluR-dependent LTD. PMID:27847432

  13. System identification of mGluR-dependent long-term depression.

    PubMed

    Tambuyzer, Tim; Ahmed, Tariq; Taylor, C James; Berckmans, Daniel; Balschun, Detlef; Aerts, Jean-Marie

    2013-03-01

    Recent advances have started to uncover the underlying mechanisms of metabotropic glutamate receptor (mGluR)-dependent long-term depression (LTD). However, it is not completely clear how these mechanisms are linked, and it is believed that several crucial mechanisms remain to be revealed. In this study, we investigated whether system identification (SI) methods can be used to gain insight into the mechanisms of synaptic plasticity. SI methods have been shown to be an objective and powerful approach for describing how sensory neurons encode information about stimuli. However, to our knowledge, it is the first time that SI methods have been applied to electrophysiological brain slice recordings of synaptic plasticity responses. The results indicate that the SI approach is a valuable tool for reverse-engineering of mGluR-LTD responses. We suggest that such SI methods can aid in unraveling the complexities of synaptic function.

  14. FAIM-L regulation of XIAP degradation modulates Synaptic Long-Term Depression and Axon Degeneration

    PubMed Central

    Martínez-Mármol, Ramón; Barneda-Zahonero, Bruna; Soto, David; Andrés, Rosa Maria; Coccia, Elena; Gasull, Xavier; Planells-Ferrer, Laura; Moubarak, Rana S.; Soriano, Eduardo; Comella, Joan X.

    2016-01-01

    Caspases have recently emerged as key regulators of axonal pruning and degeneration and of long-term depression (LTD), a long-lasting form of synaptic plasticity. However, the mechanism underlying these functions remains unclear. In this context, XIAP has been shown to modulate these processes. The neuron-specific form of FAIM protein (FAIM-L) is a death receptor antagonist that stabilizes XIAP protein levels, thus preventing death receptor-induced neuronal apoptosis. Here we show that FAIM-L modulates synaptic transmission, prevents chemical-LTD induction in hippocampal neurons, and thwarts axon degeneration after nerve growth factor (NGF) withdrawal. Additionally, we demonstrate that the participation of FAIM-L in these two processes is dependent on its capacity to stabilize XIAP protein levels. Our data reveal FAIM-L as a regulator of axonal degeneration and synaptic plasticity. PMID:27767058

  15. Presynaptic long-term depression mediated by Gi/o-coupled receptors

    PubMed Central

    Atwood, Brady K.; Lovinger, David M.; Mathur, Brian N.

    2014-01-01

    Long-term depression (LTD) of the efficacy of synaptic transmission is now recognized as an important mechanism for regulation of information storage and control of actions, as well as synapse, neuron, and circuit development. Studies of LTD mechanisms have focused mainly on postsynaptic AMPA receptor trafficking. However, the focus has now expanded to include presynaptically expressed plasticity; the predominant form being initiated by presynaptically expressed Gi/o-coupled metabotropic receptor (Gi/o-GPCR) activation. Several forms of LTD involving activation of different presynaptic Gi/o-GPCRs as a “common pathway” are described. Here, we review the literature on presynaptic Gi/o-GPCR-mediated LTD, discuss known mechanisms, gaps in our knowledge, and evaluate if all Gi/o-GPCR are capable of inducing presynaptic LTD. PMID:25160683

  16. [Comparative efficacy and tolerability of paroxetine and amitriptiline in long-term therapy preventing depressive recurrences].

    PubMed

    Mosolov, S N; Kostiukova, E G; Gorodnichev, A V; Timofeev, I V

    2005-01-01

    An open comparative randomized study of paroxetine (selective inhibitor of serotonin re-uptake) and tricyclic antidepressant amitriptiline has been conducted. These drugs were used for the treatment of 43 patients with recurrent depression (RD) with frequent relapses (ICD-10 F33.0-F33.2) during 12 months. There were 2 groups matched for demographic and clinical data, one included 21 patients treated by paroxetine and the other 22 patients switched to amitriptiline. Basing on clinical records and scores on a number of scales, i.e. HAM-D, CGI, quality of life, high efficacy of the drugs was confirmed, being estimated as 90,5% responders in the paroxetine group and 69,2% in the amitriptiline one, with the marked advantage of the former medication. The better tolerability, possibility of single intake and absence of severe side-effects argue for preferable use of paroxetine during long-term therapy in RD patients with frequent relapses.

  17. Presynaptic long-term depression mediated by Gi/o-coupled receptors.

    PubMed

    Atwood, Brady K; Lovinger, David M; Mathur, Brian N

    2014-11-01

    Long-term depression (LTD) of the efficacy of synaptic transmission is now recognized as an important mechanism for the regulation of information storage and the control of actions, as well as for synapse, neuron, and circuit development. Studies of LTD mechanisms have focused mainly on postsynaptic AMPA-type glutamate receptor trafficking. However, the focus has now expanded to include presynaptically expressed plasticity, the predominant form being initiated by presynaptically expressed Gi/o-coupled metabotropic receptor (Gi/o-GPCR) activation. Several forms of LTD involving activation of different presynaptic Gi/o-GPCRs as a 'common pathway' are described. We review here the literature on presynaptic Gi/o-GPCR-mediated LTD, discuss known mechanisms, gaps in our knowledge, and evaluate whether all Gi/o-GPCRs are capable of inducing presynaptic LTD.

  18. Anisomycin inhibits the late maintenance of long-term depression in rat hippocampal slices in vitro.

    PubMed

    Sajikumar, Sreedharan; Frey, Julietta U

    2003-02-27

    Studies were performed to investigate whether electrically-induced long-term depression (LTD) within rat hippocampal slices in vitro shares any common cellular features with LTD in the intact animal, with particular emphasis being placed on mechanisms required for its late maintenance. Our initial studies have led to the development of stimulation protocols which are able to reliably produce different forms of LTD. Depending on the induction protocol applied, we are able to demonstrate a transient protein synthesis-independent early-LTD with a duration of up to 3-4 h, together with a de novo protein synthesis-dependent late-LTD lasting for at least 8 h. Furthermore, we are able to show input-specific LTD within the CA1 region, with expression shown only by those synapses specifically stimulated by a low-frequency protocol. These studies are important pre-requisites to investigate mechanisms of 'synaptic tagging' and 'late-associativity' during LTD.

  19. Long-Term Use of Selective Serotonin Reuptake Inhibitors and Risk of Glaucoma in Depression Patients.

    PubMed

    Chen, Hsin-Yi; Lin, Cheng-Li; Kao, Chia-Hung

    2015-11-01

    This study investigated whether the long-term use of selective serotonin reuptake inhibitors (SSRIs) influences the risk of primary open-angle glaucoma (POAG) and primary angle-closure glaucoma (PACG) in the Chinese ethnic population in Taiwan.The authors retrieved the data under analysis from the National Health Insurance Research Database in Taiwan and identified 26,186 newly diagnosed depression patients without preexisting glaucoma. The study cohort included 13,093 patients with over 1 year of SSRI use, and a comparison cohort of 13,093 patients who had never used SSRIs. The main outcome was a diagnosis of POAG or PACG during follow-up. The authors used univariable and multivariable Cox proportional hazards regression models to assess the effects of SSRIs on the risk of POAG and PACG.The cumulative incidences of POAG and PACG between the SSRI and comparison cohorts exhibited nonsignificant differences (log-rank test P = .52 for POAG, P = .32 for PACG). The overall incidence of POAG in the SSRI cohort was nonsignificantly higher than that in the comparison cohort (1.51 versus 1.39 per 1000 person-years), with an adjusted hazard ratio of 1.07 (95% confidence interval = 0.82-1.40). The overall incidence of PACG in the SSRI cohort was nonsignificantly lower than that in the comparison cohort (0.95 versus 1.11 per 1000 person-years), with an adjusted hazard ratio of 0.85 (95% confidence interval = 0.62-1.18).The long-term use of SSRIs does not influence the risk of POAG or PACG in depression patients.

  20. Development of a Curriculum for Long-Term Care Nurses to Improve Recognition of Depression in Dementia

    ERIC Educational Resources Information Center

    Williams, Christine L.; Molinari, Victor; Bond, Jennifer; Smith, Michael; Hyer, Kathryn; Malphurs, Julie

    2006-01-01

    There is increasing recognition of the severe consequences of depression in long-term care residents with dementia. Most health care providers are unprepared to recognize and to manage the complexity of depression in dementia. Targeted educational initiatives in nursing homes are needed to address this growing problem. This paper describes the…

  1. The psychological contract: enhancing productivity and its implications for long-term care.

    PubMed

    Flannery, Raymond B

    2002-01-01

    When hired, a new employee is usually given a job description and an explanation of benefits. In addition, the employee will also have a psychological contract with the organization. This contract, often unstated, reflects the main source of the employee's motivation to work hard. This is true of all groups of employees, including long-term care staff. Common examples of psychological contracts for long-term care administrative staff include autonomy, social acceptance, and being in the forefront of cutting-edge research. An awareness of these psychological contracts can result in better "fits" between employee aspirations and relevant long-term care organization tasks so that productivity is enhanced. This article outlines the steps necessary to create these good fits in ways that benefit both the organization and its employees. These recommendations are of particular relevance to administrators and supervisors in long-term carefacilities.

  2. Depression, social support, and long-term risk for coronary heart disease in a 13-year longitudinal epidemiological study.

    PubMed

    Liu, Richard T; Hernandez, Evelyn M; Trout, Zoë M; Kleiman, Evan M; Bozzay, Melanie L

    2017-02-06

    Depression has been linked with long-term risk for a variety of physical health ailments, including coronary heart disease (CHD). Little is known about resilience factors that may attenuate this relationship. The current study assessed whether social support moderates the long-term risk for CHD associated with this disorder. Data were drawn from the Americans' Changing Lives study, a nationally representative longitudinal survey of adults in the United States. Participants (unweighted n=1636) completed initial assessments of functional social support, body mass index, recent history of major depression, CHD, hypertension, and diabetes. Participants were again assessed for CHD at a follow-up assessment 13 years later. Social support was found to moderate the relationship between depression and the occurrence of CHD 13 years later. Specifically, among individuals with low social support, depression was prospectively associated with CHD. In contrast, depression was not prospectively associated with CHD among individuals with high social support. The results indicate that social support may function as a resilience factor against the long-term cardiovascular risk associated with depression. Clinical interventions focusing on the development of social support systems are important not only for addressing depression itself, but also for associated long-term physical health outcomes.

  3. The 5-HT7 receptor triggers cerebellar long-term synaptic depression via PKC-MAPK.

    PubMed

    Lippiello, Pellegrino; Hoxha, Eriola; Speranza, Luisa; Volpicelli, Floriana; Ferraro, Angela; Leopoldo, Marcello; Lacivita, Enza; Perrone-Capano, Carla; Tempia, Filippo; Miniaci, Maria Concetta

    2016-02-01

    The 5-HT7 receptor (5-HT7R) mediates important physiological effects of serotonin, such as memory and emotion, and is emerging as a therapeutic target for the treatment of cognitive disorders and depression. Although previous studies have revealed an expression of 5-HT7R in cerebellum, particularly at Purkinje cells, its functional role and signaling mechanisms have never been described. Using patch-clamp recordings in cerebellar slices of adult mice, we investigated the effects of a selective 5-HT7R agonist, LP-211, on the main plastic site of the cerebellar cortex, the parallel fiber-Purkinje cell synapse. Here we show that 5-HT7R activation induces long-term depression of parallel fiber-Purkinje cell synapse via a postsynaptic mechanism that involves the PKC-MAPK signaling pathway. Moreover, a 5-HT7R antagonist abolished the expression of PF-LTD, produced by pairing parallel fiber stimulation with Purkinje cell depolarization; whereas, application of a 5-HT7R agonist impaired LTP induced by 1 Hz parallel fiber stimulation. Our results indicate for the first time that 5-HT7R exerts a fine regulation of cerebellar bidirectional synaptic plasticity that might be involved in cognitive processes and neuropsychiatric disorders involving the cerebellum.

  4. [Depressive, anxiety and posttraumatic stress disorders as long-term sequelae of intensive care treatment].

    PubMed

    Kapfhammer, H-P

    2016-03-01

    Modern intensive care medicine has led to increased survival rates even after severe life-threatening medical conditions. In self-critical and multidimensional outcome research, however, it must be considered that beyond survival rates treatment on intensive care units (ICU) can also be associated with high long-term rates of depressive, anxiety and posttraumatic stress disorders. Significant correlations with increased somatic morbidity and mortality, persisting cognitive impairments and significant deficits in health-related quality of life must also be taken into consideration. Empirical analysis of the risk factors reveals that a history of premorbid depression, sociodemographic and socioeconomic variables, age, female sex, personality traits, the underlying pathophysiological condition requiring ICU treatment, mode of sedation and analgesia, life support measures, such as mechanical ventilation, manifold traumatic experiences and memories during the stay in the ICU are all of particular pathogenetic importance. In order to reduce principally modifiable risk factors several strategies are illustrated, including well-reflected intensive care sedation and analgesia, special prophylactic medication regarding the major risk of traumatic memories and posttraumatic stress disorder (PTSD), psychological and psychotherapeutic interventions in states of increased acute stress symptoms and aids for personal memories and reorientation.

  5. Coincident Activity of Converging Pathways Enables Simultaneous Long-Term Potentiation and Long-Term Depression in Hippocampal CA1 Network In Vivo

    PubMed Central

    Cao, Jun; Zhang, Xia; Xu, Lin

    2008-01-01

    Memory is believed to depend on activity-dependent changes in the strength of synapses, e.g. long-term potentiation (LTP) and long-term depression (LTD), which can be determined by the sequence of coincident pre- and postsynaptic activity, respectively. It remains unclear, however, whether and how coincident activity of converging efferent pathways can enable LTP and LTD in the pathways simultaneously. Here, we report that, in pentobarbital-anesthetized rats, stimulation (600 pulses, 5 Hz) to Schaffer preceding to commissural pathway within a 40-ms timing window induced similar magnitudes of LTP in both pathways onto synapses of CA1 neurons, with varied LTP magnitudes after reversal of the stimulation sequence. In contrast, in urethane-anesthetized or freely-moving rats, the stimulation to Schaffer preceding to commissural pathway induced Schaffer LTP and commissural LTD simultaneously within a 40-ms timing window, without affecting synaptic efficacy in the reversed stimulation sequence. Coincident activity of Schaffer pathways confirmed the above findings under pentobarbital and urethane anesthesia. Thus, coincident activity of converging afferent pathways tends to switch the pathways to be LTP only or LTP/LTD depending on the activity states of the hippocampus. This network rule strengthens the view that activity-dependent synaptic plasticity may well contribute to memory process of the hippocampal network with flexibility or stability from one state to another. PMID:18682723

  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.

  7. Long-term depression in the sensorimotor cortex induced by repeated delivery of 10 Hz trains in vivo.

    PubMed

    Werk, C M; Klein, H S; Nesbitt, C E; Chapman, C A

    2006-06-19

    Memory consolidation in the neocortex is thought to be mediated in part by bi-directional modifications of synaptic strength. The sensorimotor cortex shows marked spontaneous activity near 10 Hz during both waking and sleep in the form of electroencephalographic spindle waves, and is also sensitive to electrical activation of inputs at 10 Hz. Induction of long-term synaptic depression in corpus callosum inputs to layer V of the sensorimotor cortex of the awake, adult rat requires repeated low-frequency stimulation over many days. To determine if 10 Hz stimulation may facilitate the induction of long-term depression, we compared the amounts of long-term depression induced by conventional 1 Hz trains, repeated delivery of 450 pairs of stimulation pulses using a 100 ms interpulse interval, and 45 short, 2 s, 10 Hz trains. Each pattern was delivered daily for 10 days and was matched for total duration and number of pulses. Changes in synaptic responses were assessed by monitoring field potentials evoked by stimulation of the corpus callosum. A facilitation of synaptic responses in layer V was observed during delivery of both paired-pulse trains and 10 Hz trains. There was no significant difference in long-term depression induced by 1 Hz stimulation and repeated paired-pulse stimulation, but 10 Hz trains induced significantly greater long-term depression than 1 Hz trains in both the early monosynaptic and late polysynaptic field potential components. The effectiveness of short 10 Hz trains for the induction of long-term depression suggests that synchronous population activity at frequencies near 10 Hz such as spindle waves may contribute to endogenous synaptic depression in sensorimotor cortex.

  8. Theta pulse stimulation: a natural stimulus pattern can trigger long-term depression but fails to reverse long-term potentiation in morphine withdrawn hippocampus area CA1.

    PubMed

    Hosseinmardi, Narges; Fathollahi, Yaghoub; Naghdi, Nasser; Javan, Mohammad

    2009-11-03

    The effects of chronic morphine exposure on synaptic plasticity in the CA1 region of the hippocampal slice preparation using extracellular recordings of the population spike (PS) evoked in response to Schaffer collateral stimulation were studied. High frequency stimulation (HFS; 1X100 Hz) and theta pulse stimulation (TPS; 5 Hz trains for 3 min) were used as patterned activities. The results showed that in rats chronically treated with morphine (dependent group), TPS induced long-term depression (LTD) of PS in CA1 in the absence of in vitro morphine. This TPS-induced PS LTD was blocked in the presence of either AP5 (NMDAR antagonist) or CPX (A1 adenosine receptor antagonist) alone, but was not blocked when AP5 and CPX were co-applied. This TPS-induced PS LTD was also blocked in the presence of either 8-PT (a selective A1 adenosine receptor antagonist) or MRS1220 (a specific A3 receptor antagonist). Additionally, when TPS was applied prior to HFS, PS long-term potentiation (LTP) was blocked. However, when TPS was applied after HFS, there was no reversal of PS LTP in slices from dependent rats in contrast to controls which displayed reversal of LTP. Both the PS LTD and the absence of PS LTP reversal were blocked by in vitro application of morphine. It is concluded that morphine withdrawal was associated with greater depression of CA1 PS elicited by natural stimulus induced activity pattern. This effect was associated with changes in NMDA and adenosine receptors due to chronic morphine administration. Such an in vitro preparation could provide a novel paradigm to investigate withdrawal effects on synaptic plasticity.

  9. Long-term depression is differentially expressed in distinct lamina of hippocampal CA1 dendrites

    PubMed Central

    Ramachandran, Binu; Ahmed, Saheeb; Dean, Camin

    2015-01-01

    Information storage in CA1 hippocampal pyramidal neurons is compartmentalized in proximal vs. distal apical dendrites, cell bodies, and basal dendrites. This compartmentalization is thought to be essential for synaptic integration. Differences in the expression of long-term potentiation (LTP) in each of these compartments have been described, but less is known regarding potential differences in long-term depression (LTD). Here, to directly compare LTD expression in each compartment and to bypass possible differences in input-specificity and stimulation of presynaptic inputs, we used global application of NMDA to induce LTD. We then examined LTD expression in each dendritic sub-region—proximal and distal apical, and basal dendrites—and in cell bodies. Interestingly, we found that distal apical dendrites exhibited the greatest magnitude of LTD of all areas tested and this LTD was maintained, whereas LTD in proximal apical dendrites was not maintained. In basal dendrites, LTD was also maintained, but the magnitude of LTD was less than in distal apical dendrites. Blockade of inhibition blocked LTD maintenance in both distal apical and basal dendrites. Population spikes recorded from the cell body layer correlated with apical dendrite field EPSP (fEPSP), where LTD was maintained in distal dendrites and decayed in proximal dendrites. On the other hand, LTD of basal dendrite fEPSPs was maintained but population spike responses were not. Thus E-S coupling was distinct in basal and apical dendrites. Our data demonstrate cell autonomous differential information processing in somas and dendritic sub-regions of CA1 pyramidal neurons in the hippocampus, where LTD expression is intrinsic to distinct dendritic regions, and does not depend on the nature of stimulation and input specificity. PMID:25767434

  10. Alcohol Impairs Long-Term Depression at the Cerebellar Parallel Fiber–Purkinje Cell Synapse

    PubMed Central

    Belmeguenai, Amor; Botta, Paolo; Weber, John T.; Carta, Mario; De Ruiter, Martijn; De Zeeuw, Chris I.; Valenzuela, C. Fernando; Hansel, Christian

    2008-01-01

    Acute alcohol consumption causes deficits in motor coordination and gait, suggesting an involvement of cerebellar circuits, which play a role in the fine adjustment of movements and in motor learning. It has previously been shown that ethanol modulates inhibitory transmission in the cerebellum and affects synaptic transmission and plasticity at excitatory climbing fiber (CF) to Purkinje cell synapses. However, it has not been examined thus far how acute ethanol application affects long-term depression (LTD) and long-term potentiation (LTP) at excitatory parallel fiber (PF) to Purkinje cell synapses, which are assumed to mediate forms of cerebellar motor learning. To examine ethanol effects on PF synaptic transmission and plasticity, we performed whole cell patch-clamp recordings from Purkinje cells in rat cerebellar slices. We found that ethanol (50 mM) selectively blocked PF–LTD induction, whereas it did not change the amplitude of excitatory postsynaptic currents at PF synapses. In contrast, ethanol application reduced voltage-gated calcium currents and type 1 metabotropic glutamate receptor (mGluR1)–dependent responses in Purkinje cells, both of which are involved in PF–LTD induction. The selectivity of these effects is emphasized by the observation that ethanol did not impair PF–LTP and that PF–LTP could readily be induced in the presence of the group I mGluR antagonist AIDA or the mGluR1a antagonist LY367385. Taken together, these findings identify calcium currents and mGluR1-dependent signaling pathways as potential ethanol targets and suggest that an ethanol-induced blockade of PF–LTD could contribute to the motor coordination deficits resulting from alcohol consumption. PMID:18922952

  11. Socioeconomic position predicts long-term depression trajectory: a 13-year follow-up of the GAZEL cohort study.

    PubMed

    Melchior, M; Chastang, J-F; Head, J; Goldberg, M; Zins, M; Nabi, H; Younès, N

    2013-01-01

    Individuals with low socioeconomic position have high rates of depression; however, it is not clear whether this reflects higher incidence or longer persistence of disorder. Past research focused on high-risk samples, and risk factors of long-term depression in the population are less well known. Our aim was to test the hypothesis that socioeconomic position predicts depression trajectory over 13 years of follow-up in a community sample. We studied 12 650 individuals participating in the French GAZEL study. Depression was assessed by the Center for Epidemiological Studies-Depression scale in 1996, 1999, 2002, 2005 and 2008. These five assessments served to estimate longitudinal depression trajectories (no depression, decreasing depression, intermediate/increasing depression, persistent depression). Socioeconomic position was measured by occupational grade. Covariates included year of birth, marital status, tobacco smoking, alcohol consumption, body mass index, negative life events and preexisting psychological and non-psychological health problems. Data were analyzed using multinomial regression, separately in men and women. Overall, participants in intermediate and low occupational grades were significantly more likely than those in high grades to have an unfavorable depression trajectory and to experience persistent depression (age-adjusted ORs: respectively 1.40, 95% confidence interval (CI) 1.16-1.70 and 2.65, 95% CI 2.04-3.45 in men, 2.48, 95% CI 1.36-4.54 and 4.53, 95% CI 2.38-8.63 in women). In multivariate models, the socioeconomic gradient in long-term depression decreased by 21-59% in men and women. Long-term depression trajectories appear to follow a socioeconomic gradient; therefore, efforts aiming to reduce the burden of depression should address the needs of the whole population rather than exclusively focus on high-risk groups.

  12. Early Impairment of Long-Term Depression in the Perirhinal Cortex of a Mouse Model of Alzheimer's Disease

    PubMed Central

    Tamagnini, Francesco; Burattini, Costanza; Casoli, Tiziana; Balietti, Marta; Fattoretti, Patrizia

    2012-01-01

    Abstract Visual recognition memory is early impaired in Alzheimer's disease. Long-term depression of synaptic transmission in the perirhinal cortex is critically involved in this form of memory. We found that synaptic transmission was impaired in perirhinal cortex slices obtained from 3-month-old Tg2576 mice, and that 3,000 pulses at 5 Hz induced long-term depression in perirhinal cortex slices from age-matched control mice, but not in those from Tg2576 mice. To our knowledge, these data provide the first evidence of synaptic transmission and long-term depression impairment in the perirhinal cortex in an animal model of Alzheimer's disease, and the earliest synaptic deficit in Tg2576 mice. PMID:22533438

  13. Presynaptic Spike Timing-Dependent Long-Term Depression in the Mouse Hippocampus

    PubMed Central

    Andrade-Talavera, Yuniesky; Duque-Feria, Paloma; Paulsen, Ole; Rodríguez-Moreno, Antonio

    2016-01-01

    Spike timing-dependent plasticity (STDP) is a Hebbian learning rule important for synaptic refinement during development and for learning and memory in the adult. Given the importance of the hippocampus in memory, surprisingly little is known about the mechanisms and functions of hippocampal STDP. In the present work, we investigated the requirements for induction of hippocampal spike timing-dependent long-term potentiation (t-LTP) and spike timing-dependent long-term depression (t-LTD) and the mechanisms of these 2 forms of plasticity at CA3-CA1 synapses in young (P12–P18) mouse hippocampus. We found that both t-LTP and t-LTD can be induced at hippocampal CA3-CA1 synapses by pairing presynaptic activity with single postsynaptic action potentials at low stimulation frequency (0.2 Hz). Both t-LTP and t-LTD require NMDA-type glutamate receptors for their induction, but the location and properties of these receptors are different: While t-LTP requires postsynaptic ionotropic NMDA receptor function, t-LTD does not, and whereas t-LTP is blocked by antagonists at GluN2A and GluN2B subunit-containing NMDA receptors, t-LTD is blocked by GluN2C or GluN2D subunit-preferring NMDA receptor antagonists. Both t-LTP and t-LTD require postsynaptic Ca2+ for their induction. Induction of t-LTD also requires metabotropic glutamate receptor activation, phospholipase C activation, postsynaptic IP3 receptor-mediated Ca2+ release from internal stores, postsynaptic endocannabinoid (eCB) synthesis, activation of CB1 receptors and astrocytic signaling, possibly via release of the gliotransmitter d-serine. We furthermore found that presynaptic calcineurin is required for t-LTD induction. t-LTD is expressed presynaptically as indicated by fluctuation analysis, paired-pulse ratio, and rate of use-dependent depression of postsynaptic NMDA receptor currents by MK801. The results show that CA3-CA1 synapses display both NMDA receptor-dependent t-LTP and t-LTD during development and identify a

  14. Long-Term Effects of Bereavement and Caregiver Intervention on Dementia Caregiver Depressive Symptoms

    ERIC Educational Resources Information Center

    Haley, William E.; Bergman, Elizabeth J.; Roth, David L.; McVie, Theresa; Gaugler, Joseph E.; Mittelman, Mary S.

    2008-01-01

    Purpose: The purpose of this study was to examine the joint effects of bereavement and caregiver intervention on caregiver depressive symptoms. Design and Methods: Alzheimer's caregivers from a randomized trial of an enhanced caregiver support intervention versus usual care who had experienced the death of their spouse (n = 254) were repeatedly…

  15. 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…

  16. A Computational Model for the AMPA Receptor Phosphorylation Master Switch Regulating Cerebellar Long-Term Depression.

    PubMed

    Gallimore, Andrew R; Aricescu, A Radu; Yuzaki, Michisuke; Calinescu, Radu

    2016-01-01

    The expression of long-term depression (LTD) in cerebellar Purkinje cells results from the internalisation of α-amino-3-hydroxy-5-methylisoxazole-4-propionic acid receptors (AMPARs) from the postsynaptic membrane. This process is regulated by a complex signalling pathway involving sustained protein kinase C (PKC) activation, inhibition of serine/threonine phosphatase, and an active protein tyrosine phosphatase, PTPMEG. In addition, two AMPAR-interacting proteins-glutamate receptor-interacting protein (GRIP) and protein interacting with C kinase 1 (PICK1)-regulate the availability of AMPARs for trafficking between the postsynaptic membrane and the endosome. Here we present a new computational model of these overlapping signalling pathways. The model reveals how PTPMEG cooperates with PKC to drive LTD expression by facilitating the effect of PKC on the dissociation of AMPARs from GRIP and thus their availability for trafficking. Model simulations show that LTD expression is increased by serine/threonine phosphatase inhibition, and negatively regulated by Src-family tyrosine kinase activity, which restricts the dissociation of AMPARs from GRIP under basal conditions. We use the model to expose the dynamic balance between AMPAR internalisation and reinsertion, and the phosphorylation switch responsible for the perturbation of this balance and for the rapid plasticity initiation and regulation. Our model advances the understanding of PF-PC LTD regulation and induction, and provides a validated extensible platform for more detailed studies of this fundamental synaptic process.

  17. A Computational Model for the AMPA Receptor Phosphorylation Master Switch Regulating Cerebellar Long-Term Depression

    PubMed Central

    Gallimore, Andrew R.; Aricescu, A. Radu; Yuzaki, Michisuke; Calinescu, Radu

    2016-01-01

    The expression of long-term depression (LTD) in cerebellar Purkinje cells results from the internalisation of α-amino-3-hydroxy-5-methylisoxazole-4-propionic acid receptors (AMPARs) from the postsynaptic membrane. This process is regulated by a complex signalling pathway involving sustained protein kinase C (PKC) activation, inhibition of serine/threonine phosphatase, and an active protein tyrosine phosphatase, PTPMEG. In addition, two AMPAR-interacting proteins–glutamate receptor-interacting protein (GRIP) and protein interacting with C kinase 1 (PICK1)–regulate the availability of AMPARs for trafficking between the postsynaptic membrane and the endosome. Here we present a new computational model of these overlapping signalling pathways. The model reveals how PTPMEG cooperates with PKC to drive LTD expression by facilitating the effect of PKC on the dissociation of AMPARs from GRIP and thus their availability for trafficking. Model simulations show that LTD expression is increased by serine/threonine phosphatase inhibition, and negatively regulated by Src-family tyrosine kinase activity, which restricts the dissociation of AMPARs from GRIP under basal conditions. We use the model to expose the dynamic balance between AMPAR internalisation and reinsertion, and the phosphorylation switch responsible for the perturbation of this balance and for the rapid plasticity initiation and regulation. Our model advances the understanding of PF-PC LTD regulation and induction, and provides a validated extensible platform for more detailed studies of this fundamental synaptic process. PMID:26807999

  18. The effects of light therapy on depression and sleep disruption in older adults in a long-term care facility.

    PubMed

    Wu, Mann-Chian; Sung, Huei-Chuan; Lee, Wen-Li; Smith, Graeme D

    2015-10-01

    This study aims to evaluate the effect of light therapy on depression and sleep disruption in older adults residing in a long-term care facility. Psychological morbidity is a problem commonly seen in older adults residing in long-term care facilities. Limited research has addressed the effect of light therapy on depression in this population. A quasi-experimental pretest and posttest design was used. Thirty-four participants in the experimental group received light therapy by sitting in front of a 10000-lux light box 30 min in the morning, three times a week for 4 weeks. Thirty-one participants in the control group received routine care without light therapy. Depression was measured by Geriatric Depression Scale-Short Form at baseline and week 4. After receiving 4 weeks of light therapy, the mean depression score in the experimental group decreased from 7.24 (SD3.42) at pretest to 5.91 (SD 3.40) at posttest, and had a significant reduction (t = 2.22, P = 0.03). However, there was no significant difference in depression score and sleep disruption between the experimental group and control group. Light therapy might have the potential to reduce depressive symptoms and sleep disruption and may be a viable intervention to improve mental health of older adults in the long-term care facilities.

  19. Long Term Trends in Carbon Dioxide Enhancements in an Urban Region

    NASA Astrophysics Data System (ADS)

    Mitchell, L.; Lin, J. C.; Bowling, D. R.; Pataki, D. E.; Strong, C.; Schauer, A. J.; Bares, R.; Bush, S. E.; Holland, L.; Mallia, D.; Ehleringer, J. R.

    2014-12-01

    Urban regions are characterized by highly concentrated emissions of greenhouse gases, accounting for an estimated ~70% of global fossil fuel CO2 emissions from energy usage. Traditional long-term measurement networks designed to constrain the global carbon budget have sites situated in remote regions far from urban centers, rendering such sites unable to resolve signatures of spatial and temporal variability from urban emissions. Here we present a unique, long-term record of CO2 concentrations at five locations ranging from rapidly growing to fully mature urban regions in Utah's Salt Lake Valley, based on continuous measurements since 2001. Trends in concentration enhancements above background levels were found to vary throughout the valley, with mature urban areas (Salt Lake City) exhibiting declining CO2 enhancements and previously rural areas undergoing urban growth, having increasing CO2 enhancements. Furthermore, divergent trends were observed at different times of the day, potentially indicating long-term changes in emissions from different contributing sources. Multiple hypotheses to explain the trends in CO2 enhancements will be discussed, including changes in socioeconomic (e.g., population, traffic, energy efficiency) and meteorological (e.g., atmospheric mixing heights, temperatures) factors. This spatially distributed long-term CO2 monitoring network also provides a case study for understanding factors relevant to the design of urban trace gas observatories.

  20. 77 FR 12227 - Long Term 2 Enhanced Surface Water Treatment Rule: Uncovered Finished Water Reservoirs; Public...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-02-29

    ... AGENCY 40 CFR Parts 141 and 142 Long Term 2 Enhanced Surface Water Treatment Rule: Uncovered Finished Water Reservoirs; Public Meeting AGENCY: Environmental Protection Agency (EPA). ACTION: Notice of public..., concerning information that may inform the regulatory review of the uncovered finished water...

  1. Long-term depression and associativity in rat primary motor cortex following thalamic stimulation.

    PubMed

    Eckert, M J; Racine, R J

    2006-12-01

    Associativity is an attractive property of LTP in terms of its possible mechanism as a model for memory storage. In this study, we compare the effects of homosynaptic vs. associative stimulation on the induction of LTP and LTD in the neocortex of freely behaving rats. Using a callosal input to the motor cortex as a 'strong' input (one that potentiates reliably following homosynaptic stimulation), we paired activity of this pathway with a 'weak' thalamocortical pathway (one that does not potentiate when stimulated homosynaptically). Surprisingly, homosynaptic HFS caused a lasting depression of the field EPSP in the thalamocortical pathway. Analysis of this effect revealed that it was largely polysynaptic. Associative HFS (HFS applied to both pathways) not only failed to induce an LTP effect in the thalamocortical pathway, it increased the magnitude of the depression. Associative HFS did, however, facilitate LTP induction in the 'strong' callosal pathway. When comparing the effects of homosynaptic and associative LTD induction (HFS on one pathway anticorrelated with LFS on the other), we found that both protocols induced a similar magnitude of depression. These results show that HFS applied to the thalamocortical pathway causes a depression and this depression is enhanced, not reversed, by associative pairing with a strong input.

  2. Post-Training Intrahippocampal Inhibition of Class I Histone Deacetylases Enhances Long-Term Object-Location Memory

    ERIC Educational Resources Information Center

    Hawk, Joshua D.; Florian, Cedrick; Abel, Ted

    2011-01-01

    Long-term memory formation involves covalent modification of the histone proteins that package DNA. Reducing histone acetylation by mutating histone acetyltransferases impairs long-term memory, and enhancing histone acetylation by inhibiting histone deacetylases (HDACs) improves long-term memory. Previous studies using HDAC inhibitors to enhance…

  3. A Videotape-Based Training Method for Improving the Detection of Depression in Residents of Long-Term Care Facilities

    ERIC Educational Resources Information Center

    Wood, Stacey; Cummings, Jeffrey L.; Schnelle, Betha; Stephens, Mary

    2002-01-01

    Purpose: This article reviews the effectiveness of a new training program for improving nursing staffs' detection of depression within long-term care facilities. The course was designed to increase recognition of the Minimal Data Set (MDS) Mood Trigger items, to be brief, and to rely on images rather than didactics. Design and Methods: This study…

  4. Acceptance and Commitment Therapy for Depression: A Preliminary Randomized Clinical Trial for Unemployed on Long-Term Sick Leave

    ERIC Educational Resources Information Center

    Folke, Fredrik; Parling, Thomas; Melin, Lennart

    2012-01-01

    This preliminary study investigated the feasibility of a brief Acceptance and Commitment Therapy (ACT) in a Swedish sample of unemployed individuals on long-term sick leave due to depression. Participants were randomized to a nonstandardized control condition (N = 16) or to the ACT condition (N = 18) consisting of 1 individual and 5 group…

  5. The Longitudinal Relationship between the Use of Long-Term Care and Depressive Symptoms in Older Adults

    ERIC Educational Resources Information Center

    Pot, Anne Margriet; Deeg, Dorly J.H.; Twisk, Jos W.R.; Beekman, Aartjan T.F.; Zarit, Steven H.

    2005-01-01

    Purpose: The aim of this study was to estimate the longitudinal relationship between transitions in the use of long-term care and older adults' depressive symptoms and to investigate whether this relationship could be explained by markers of older adults' underlying health, or other variables including demographics, personality, and partner…

  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. Effectiveness and outcome predictors of long-term lithium prophylaxis in unipolar major depressive disorder

    PubMed Central

    Baethge, Christopher; Gruschka, Philipp; Smolka, Michael N.; Berghöfer, Anne; Bschor, Tom; Müller-Oerlinghausen, Bruno; Bauer, Michael

    2003-01-01

    Objective To determine the effectiveness of lithium prophylaxis in unipolar major depressive disorder (MDD) and to identify predictors of outcome including comedication. Methods In this long-term naturalistic study, clinical data from 55 patients with MDD (DSM-III-R) were collected prospectively in an outpatient clinic specializing in the treatment of affective disorders. Outcome measures Change in hospital admission rate (number and duration) during prophylaxis compared with the period before prophylaxis, Morbidity-Index during prophylaxis and time to first recurrence after initiation of lithium treatment. Results During an average follow-up period of 6.7 years, a significant decline in the number of days spent in hospital (p < 0.001; 52 d/yr less; 95; CI 31–73 d) and a low Morbidity-Index (mean 0.07) was observed. Only in 6 patients did medication have to be changed because of side-effects (n = 4) or a lack of efficacy (n = 2). None of the independent variables we analyzed proved to be important in predicting the outcome of lithium prophylaxis. Comedication was necessary in 21 patients. The overall outcome of their prophylactic treatment, however, did not differ from the group that did not receive comedication in the symptom-free intervals. Conclusions The results of this study, with its long observation period and the inclusion of comedication as a confounding variable, indicate that lithium is a potent prophylactic agent for unipolar MDD in a naturalistic setting. In contrast to the findings of others, age was not associated with the outcome of prophylaxis, and latency did not predict outcome. Contrary to doubts that have been raised in recent years with regard to the effectiveness of lithium in everyday clinical practice, lithium appears to be a safe and potent alternative to antidepressants. PMID:14517579

  8. Nicotine uses neuron-glia communication to enhance hippocampal synaptic transmission and long-term memory.

    PubMed

    López-Hidalgo, Mónica; Salgado-Puga, Karla; Alvarado-Martínez, Reynaldo; Medina, Andrea Cristina; Prado-Alcalá, Roberto A; García-Colunga, Jesús

    2012-01-01

    Nicotine enhances synaptic transmission and facilitates long-term memory. Now it is known that bi-directional glia-neuron interactions play important roles in the physiology of the brain. However, the involvement of glial cells in the effects of nicotine has not been considered until now. In particular, the gliotransmitter D-serine, an endogenous co-agonist of NMDA receptors, enables different types of synaptic plasticity and memory in the hippocampus. Here, we report that hippocampal long-term synaptic plasticity induced by nicotine was annulled by an enzyme that degrades endogenous D-serine, or by an NMDA receptor antagonist that acts at the D-serine binding site. Accordingly, both effects of nicotine: the enhancement of synaptic transmission and facilitation of long-term memory were eliminated by impairing glial cells with fluoroacetate, and were restored with exogenous D-serine. Together, these results show that glial D-serine is essential for the long-term effects of nicotine on synaptic plasticity and memory, and they highlight the roles of glial cells as key participants in brain functions.

  9. Long-Term Fine Particulate Matter Exposure and Major Depressive Disorder in a Community-Based Urban Cohort

    PubMed Central

    Kim, Kyoung-Nam; Lim, Youn-Hee; Bae, Hyun Joo; Kim, Myounghee; Jung, Kweon; Hong, Yun-Chul

    2016-01-01

    Background: Previous studies have associated short-term air pollution exposure with depression. Although an animal study showed an association between long-term exposure to particulate matter ≤ 2.5 μm (PM2.5) and depression, epidemiological studies assessing the long-term association are scarce. Objective: We aimed to determine the association between long-term PM2.5 exposure and major depressive disorder (MDD). Methods: A total of 27,270 participants 15–79 years of age who maintained an address within the same districts in Seoul, Republic of Korea, throughout the entire study period (between 2002 and 2010) and without a previous MDD diagnosis were analyzed. We used three district-specific exposure indices as measures of long-term PM2.5 exposure. Cox proportional hazards models adjusted for potential confounding factors and measured at district and individual levels were constructed. We further conducted stratified analyses according to underlying chronic diseases such as diabetes mellitus, cardiovascular disease, and chronic obstructive pulmonary disease. Results: The risk of MDD during the follow-up period (2008–2010) increased with an increase of 10 μg/m3 in PM2.5 in 2007 [hazard ratio (HR) = 1.44; 95% CI: 1.17, 1.78], PM2.5 between 2007 and 2010 (HR = 1.59; 95% CI: 1.02, 2.49), and 12-month moving average of PM2.5 until an event or censor (HR = 1.47; 95% CI: 1.14, 1.90). The association between long-term PM2.5 exposure and MDD was greater in participants with underlying chronic diseases than in participants without these diseases. Conclusion: Long-term PM2.5 exposure increased the risk of MDD among the general population. Individuals with underlying chronic diseases are more vulnerable to long-term PM2.5 exposure. Citation: Kim KN, Lim YH, Bae HJ, Kim M, Jung K, Hong YC. 2016. Long-term fine particulate matter exposure and major depressive disorder in a community-based urban cohort. Environ Health Perspect 124:1547–1553; http://dx.doi.org/10

  10. The long-term effects of methamphetamine exposure during pre-adolescence on depressive-like behaviour in a genetic animal model of depression.

    PubMed

    Mouton, Moné; Harvey, Brian H; Cockeran, Marike; Brink, Christiaan B

    2016-02-01

    Methamphetamine (METH) is a psychostimulant and drug of abuse, commonly used early in life, including in childhood and adolescence. Adverse effects include psychosis, anxiety and mood disorders, as well as increased risk of developing a mental disorder later in life. The current study investigated the long-term effects of chronic METH exposure during pre-adolescence in stress-sensitive Flinders Sensitive Line (FSL) rats (genetic model of depression) and control Flinders Resistant Line (FRL) rats. METH or vehicle control was administered twice daily from post-natal day 19 (PostND19) to PostND34, followed by behavioural testing at either PostND35 (early effects) or long-lasting after withdrawal at PostND60 (early adulthood). Animals were evaluated for depressive-like behaviour, locomotor activity, social interaction and object recognition memory. METH reduced depressive-like behaviour in both FSL and FRL rats at PostND35, but enhanced this behaviour at PostND60. METH also reduced locomotor activity on PostND35 in both FSL and FRL rats, but without effect at PostND60. Furthermore, METH significantly lowered social interaction behaviour (staying together) in both FRL and FSL rats at PostND35 and PostND60, whereas self-grooming time was significantly reduced only at PostND35. METH treatment enhanced exploration of the familiar vs. novel object in the novel object recognition test (nORT) in FSL and FRL rats on PostND35 and PostND60, indicative of reduced cognitive performance. Thus, early-life METH exposure induce social and cognitive deficits. Lastly, early-life exposure to METH may result in acute antidepressant-like effects immediately after chronic exposure, whereas long-term effects after withdrawal are depressogenic. Data also supports a role for genetic predisposition as with FSL rats.

  11. Daily activity level improvement with antidepressant medications predicts long-term clinical outcomes in outpatients with major depressive disorder

    PubMed Central

    Jha, Manish K; Teer, Raymond B; Minhajuddin, Abu; Greer, Tracy L; Rush, A John; Trivedi, Madhukar H

    2017-01-01

    Background Major depressive disorder (MDD) significantly impacts performance of both work- and nonwork-related routine daily activities. We have shown that work productivity is significantly impaired in employed MDD patients, but the extent of impairments in nonwork-related routine activities and its association with antidepressant treatment outcomes has not been established. Materials and methods Activity impairment was measured using the sixth item of Work Productivity and Activity Impairment Scale in the Combining Medications to Enhance Depression Outcomes (CO-MED) trial (n=665). Published norms were used to define activity impairment levels. The relationship between activity impairment and baseline sociodemographic and clinical characteristics was evaluated along with changes in activity impairment and its relationship with other clinical outcomes such as symptom severity, function, and side effect burden. Remission status at 3 and 7 months was predicted based on week 6 activity impairment level. Results Higher psychosocial and cognitive impairments and greater number of comorbid medical conditions were associated with greater activity impairment at baseline. Proportion of participants with severe activity impairment declined from 47.6% at baseline to 18.7% at 3 months, while mean activity impairment decreased from 57.1 at baseline to 32.8 at 3 months. During course of treatment, levels of activity impairment correlated most strongly with psychosocial function among measures of symptom severity, function, quality of life, and side effect burden. No or minimal activity impairment at week 6 was associated with two to three times higher rates of remission at 3 and 7 months as compared to moderate or severe activity impairment levels even after controlling for remission status at week 6 and select baseline variables. Conclusion Depressed patients have high levels of nonwork-related activity impairment at baseline that improves significantly with treatment and

  12. The Relationship Between Depressive Symptoms and Social Cognitive Processing in Partners of Long-Term Breast Cancer Survivors

    PubMed Central

    Cohee, Andrea A.; Adams, Rebecca N.; Fife, Betsy L.; Von Ah, Diane M.; Monahan, Patrick O.; Zoppi, Kathleen A.; Cella, David; Champion, Victoria L.

    2016-01-01

    Purpose/Objectives To determine 1) if depressive symptoms in partners of long-term breast cancer survivors (BCS) could be predicted by social cognitive processing theory, and 2) if partners of younger and older breast cancer survivors were differentially affected by the cancer experience. Design A cross-sectional, descriptive study utilizing self-report questionnaires. Setting Indiana University and 97 ECOG-ACRIN sites. Sample Partners of breast cancer survivors (n=508) diagnosed 3–8 years prior. Methods Secondary data mediation analyses were conducted to determine if cognitive processing mediated the relationship between social constraints and depressive symptoms. Age-related differences on all scales were tested. Main Research Variables Depressive symptoms; secondary variables included social constraints, cognitive processing (avoidance and intrusive thoughts), and potentially confounding variables. Findings Cognitive processing mediated the relationship between social constraints and depressive symptoms for partners (F(5,498) = 19.911, R2=.167, p<.001). Partners of young BCS reported worse outcomes on all measures than partners of older breast cancer survivors Conclusions As predicted by the social cognitive processing theory, cognitive processing mediated the relationship between social constraints and depressive symptoms. Furthermore, partners of younger BCS fared worse on social constraints, intrusive thoughts and depressive symptoms than partners of older BCS. Implications for Nursing Results provide support for using the social cognitive processing theory in intervention design with partners of long-term BCS to decrease depressive symptoms. PMID:27991603

  13. Forebrain NR2B overexpression enhancing fear acquisition and long-term potentiation in the lateral amygdala.

    PubMed

    Duan, Yanhong; Zhou, Siqi; Ma, Jing; Yin, Pengcheng; Cao, Xiaohua

    2015-09-01

    N-methyl-d-aspartic acid (NMDA) receptor-dependent long-term potentiation (LTP) at the thalamus-lateral amygdala (T-LA) synapses is the basis for acquisition of auditory fear memory. However, the role of the NMDA receptor NR2B subunit in synaptic plasticity at T-LA synapses remains speculative. In the present study, using transgenic mice with forebrain-specific overexpression of the NR2B subunit, we have observed that forebrain NR2B overexpression results in enhanced LTP but does not alter long-term depression (LTD) at the T-LA synapses in transgenic mice. To elucidate the cellular mechanisms underlying enhanced LTP at T-LA synapses in these transgenic mice, AMPA and NMDA receptor-mediated postsynaptic currents have been measured. The data show a marked increasing in the amplitude and decay time of NMDA receptor-mediated currents in these transgenic mice. Consistent with enhanced LTP at T-LA synapses, NR2B-transgenic mice exhibit better performance in the acquisition of auditory fear memory than wild-type littermates. Our results demonstrate that up-regulation of NR2B expression facilitates acquisition of auditory cued fear memory and enhances LTP at T-LA synapses.

  14. X-Ray Enhancement and Long-term Evolution of Swift J1822.3-1606

    NASA Astrophysics Data System (ADS)

    Benli, Onur; Çalışkan, Ş.; Ertan, Ü.; Alpar, M. A.; Trümper, J. E.; Kylafis, N. D.

    2013-12-01

    We investigate the X-ray enhancement and the long-term evolution of the recently discovered second "low-B magnetar" Swift J1822.3-1606 in the frame of the fallback disk model. During a soft gamma burst episode, the inner disk matter is pushed back to larger radii, forming a density gradient at the inner disk. Subsequent relaxation of the inner disk could account for the observed X-ray enhancement light curve of Swift J1822.3-1606. We obtain model fits to the X-ray data with basic disk parameters similar to those employed to explain the X-ray outburst light curves of other anomalous X-ray pulsars and soft gamma repeaters. The long period (8.4 s) of the neutron star can be reached by the effect of the disk torques in the long-term accretion phase ((1-3) × 105 yr). The currently ongoing X-ray enhancement could be due to a transient accretion epoch, or the source could still be in the accretion phase in quiescence. Considering these different possibilities, we determine the model curves that could represent the long-term rotational and the X-ray luminosity evolution of Swift J1822.3-1606, which constrain the strength of the magnetic dipole field to the range of (1-2) × 1012 G on the surface of the neutron star.

  15. Cocaine withdrawal impairs metabotropic glutamate receptor-dependent long-term depression in the nucleus accumbens.

    PubMed

    Huang, Chiung-Chun; Yeh, Che-Ming; Wu, Mei-Ying; Chang, Alice Y W; Chan, Julie Y H; Chan, Samuel H H; Hsu, Kuei-Sen

    2011-03-16

    Neuroadaptation in the nucleus accumbens (NAc), a central component of the mesolimbic dopamine (DA) system, has been implicated in the development of cocaine-induced psychomotor sensitization and relapse to cocaine seeking. However, little is known about the cellular and synaptic mechanisms underlying such adaptation. Using a mouse model of behavioral sensitization, we show that animals withdrawn from repeated cocaine exposure have a selective deficit in the ability to elicit metabotropic glutamate receptor (mGluR)-dependent long-term depression (LTD) in the shell of the NAc in response to bath application of the group I mGluR agonist (S)-3,5-dihydroxyphenylglycine (DHPG). Experiments conducted in the presence of the selective mGluR1 antagonists 7-(hydroxyimino)cyclopropachromen-carboxylate ethyl ester and (S)-(+)-α-amino-4-carboxy-2-methylbenzeneacetic acid, or the mGluR5 antagonist 2-methyl-6-(phenylethynyl)-pyridine, demonstrated that the impaired DHPG-LTD is likely attributable to a loss of mGluR5 function. Quantitative real-time reverse transcriptase-PCR and Western blot analysis revealed significant downregulation of mGluR5, but not mGluR1, mRNA and protein levels in the NAc shell. The inhibitory effect of repeated cocaine exposure on DHPG-LTD was selectively prevented when cocaine was coadministered with the selective D(1)-like DA receptor antagonist (R)-(+)-7-chloro-8-hydroxy-3-methyl-1-phenyl-2,3,4,5-tetrahydro-1H-3-benzazepine. Furthermore, the levels of brain-derived neurotrophic factor (BDNF) protein in the NAc shell increased progressively after cocaine withdrawal, and the impairment of DHPG-LTD in the NAc shell was not found in slices from BDNF-knock-out mice after cocaine withdrawal. These results suggest that withdrawal from repeated cocaine exposure may result in increased BDNF levels in the NAc shell, which leads to a selective downregulation of mGluR5 and thereby impairs the induction of mGluR-dependent LTD.

  16. Analysis of the Italian generic medicines retail market: recommendations to enhance long-term sustainability.

    PubMed

    Dylst, Pieter; Vulto, Arnold; Simoens, Steven

    2015-02-01

    Italy is among the European countries with the lowest uptake of generic medicines. This paper provides a perspective on the Italian generic medicines retail market. Fast market entrance of generic medicines in Italy is hindered by several factors: the existence of Complementary Protection Certificates in the past, the large market for copies and multiple cases of patent linkage. Prices of generic medicines in Italy are low compared to other European countries. To contain pharmaceutical expenditure, pharmaceutical companies are currently forced to pay back in case of overspending, which disproportionally penalizes small and fast growing companies, to which most generic companies belong to. Current demand-side policies do not successfully stimulate the use of generic medicines. The current market environment surrounding the Italian generic medicines retail market (i.e., low prices, low volumes) threatens its long-term sustainability. Recommendations to enhance the long-term sustainability of the Italian generic medicines retail market round off this perspective paper.

  17. Manitoba: enhanced orientation for nurses new to long-term care.

    PubMed

    O'Rourke, Deanne

    2012-03-01

    The Manitoba pilot project, Enhanced Orientation for Nurses New to Long-Term Care, lasted 18 months and involved three sites in the Winnipeg Regional Health Authority. It was developed to address the reality that individuals entering long-term care have more complex needs than in the past and that it is often difficult to recruit and retain nurses to work in this care setting. This mentorship program included 11 mentors and 12 protégés. As well, six clinical workshops were developed and held for a total of 390 participants. Protégés reported a positive effect on their transition to the workplace and their confidence levels, and mentors reported building their mentorship skills. The program has been expanded within the Winnipeg Region and to other health regions in the province and in Canada.

  18. Long-Term Effects of the Family Check-Up in Public Secondary School on Diagnosed Major Depressive Disorder in Adulthood.

    PubMed

    Connell, Arin M; Dishion, Thomas J

    2017-03-01

    Given the public health importance of depression, the identification of prevention programs with long-term effects on reducing the rate of depression is of critical importance, as is the examination of factors that may moderate the magnitude of such prevention effects. This study examines the impact of the Family Check-Up, delivered in public secondary schools beginning in sixth grade, on the development of major depression in adulthood (aged 28-30). The multilevel intervention program included (a) a universal classroom-based intervention focused on problem solving and peer relationship skills, (b) the Family Check-Up (selected), a brief assessment-based intervention designed to motivate parents to improve aspects of family functioning when warranted, and (c) family management treatment (indicated), focused on improving parenting skills. Demographic (gender and ethnicity) and baseline risk factors (family conflict, academic problems, antisocial behavior, and peer deviance) were examined as possible moderators in logistic regression analyses. Intervention effects on depression were moderated by baseline family conflict and academic performance, with stronger intervention effects for youth with low grade point averages and from low-conflict families at baseline. Such findings extend the emerging literature on prevention programs with long-term effects on depression, and highlight directions for future research to enhance such effects.

  19. Design Principles and Concepts for Enhancing Long-Term Cap Performance and Confidence

    SciTech Connect

    Steven J. Piet; Robert P. Breckenridge; Gregory J. White; Jacob J. Jacobson; Hilary I. Inyang

    2005-10-01

    The siting of new landfills is becoming increasing difficult as the public and stakeholders want more confidence of performance for longer times and landfill owners want to store more waste in the least area while knowing and limiting their long-term liabilities. These changes motivate re-examination of long-term performance mechanisms and their implications for cap and barrier designs. Accordingly, in this paper we first consider design principles from the standpoint of long-term performance and management, including the ability to monitor and repair barriers. We then consider some design concepts that may implement these principles, especially evapo-transpiration (ET) caps. We suggest five design principles based on experience in the cap and barrier field as well as other engineering disciplines. These principles are as follows: · Establish a clear and defendable design basis. · Design for ease of monitoring and repair. · Analyze the barrier as a dynamic system, not static. · Work with nature, not against. · Recognize that increased complexity can reduce, not enhance, net performance. ET caps are an excellent embodiment of these design principles. We apply the design principles to ET caps, as well as variants such as erosion armor, capillary breaks, bio-intrusion layers, and low permeability material layers.

  20. Long Term Sertraline Effects on Neural Structures in Depressed and Nondepressed Adult Female Nonhuman Primates

    PubMed Central

    Willard, Stephanie L.; Uberseder, Beth; Clark, Ashlee; Daunais, James B.; Johnston, Warwick D.; Neely, David; Massey, Adreanna; Williamson, Jeff D.; Kraft, Robert A.; Bourland, J. Daniel; Jones, Sara R.; Shively, Carol A.

    2015-01-01

    Background Selective serotonin reuptake inhibitors (SSRIs) are widely prescribed for mood and other disorders. However, their neural effects are difficult to study due to patient compliance and drug history variability, and rarely studied in those prescribed SSRIs for non-mood disorders. Here we evaluated SSRI effects on neural volumetrics in depressed and nondepressed monkeys. Methods 42 socially-housed cynomolgus monkeys were randomized to treatment balanced on pretreatment depressive behavior and body weight. Monkeys were trained for oral administration of placebo or 20mg/kg sertraline HCl daily for 18 months and depressive and anxious behavior recorded. Volumes of neural regions of interest in depression were measured in magnetic resonance images and analyzed by 2 (depressed, nondepressed) × 2 (placebo, sertraline) ANOVA. Results Sertraline reduced anxiety (p=0.04) but not depressive behavior (p=0.43). Left Brodmann’s Area (BA)32 was smaller in depressed than nondepressed monkeys (main effect of depression: p<0.05). Sertraline and depression status interacted to affect volumes of left anterior cingulate cortex (ACC), left BA24, right hippocampus (HC), and right anterior HC (sertraline X depression interactions: all p’s < 0.05). In the Placebo group, depressed monkeys had smaller right anterior HC and left ACC than nondepressed monkeys. In nondepressed monkeys, sertraline reduced right HC volume, especially right anterior HC volume. In depressed monkeys sertraline increased left ACC volume. In nondepressed monkeys, sertraline reduced left BA24 volumes resulting in smaller BA24 volumes in nondepressed than sertraline-treated depressed monkeys. Conclusions These observations suggest that SSRIs may differentially affect neural structures in depressed and nondepressed individuals. PMID:26116816

  1. 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

  2. LONG-TERM DEMONSTRATION OF SORBENT ENHANCEMENT ADDITIVE TECHNOLOGY FOR MERCURY CONTROL

    SciTech Connect

    Jason D. Laumb; Dennis L. Laudal; Grant E. Dunham; John P. Kay; Christopher L. Martin; Jeffrey S. Thompson; Nicholas B. Lentz; Alexander Azenkeng; Kevin C. Galbreath; Lucinda L. Hamre

    2011-05-27

    Long-term demonstration tests of advanced sorbent enhancement additive (SEA) technologies have been completed at five coal-fired power plants. The targeted removal rate was 90% from baseline conditions at all five stations. The plants included Hawthorn Unit 5, Mill Creek Unit 4, San Miguel Unit 1, Centralia Unit 2, and Hoot Lake Unit 2. The materials tested included powdered activated carbon, treated carbon, scrubber additives, and SEAs. In only one case (San Miguel) was >90% removal not attainable. The reemission of mercury from the scrubber at this facility prevented >90% capture.

  3. ASIC1a regulates insular long-term depression and is required for the extinction of conditioned taste aversion

    PubMed Central

    Li, Wei-Guang; Liu, Ming-Gang; Deng, Shining; Liu, Yan-Mei; Shang, Lin; Ding, Jing; Hsu, Tsan-Ting; Jiang, Qin; Li, Ying; Li, Fei; Zhu, Michael Xi; Xu, Tian-Le

    2016-01-01

    Acid-sensing ion channel 1a (ASIC1a) has been shown to play important roles in synaptic plasticity, learning and memory. Here we identify a crucial role for ASIC1a in long-term depression (LTD) at mouse insular synapses. Genetic ablation and pharmacological inhibition of ASIC1a reduced the induction probability of LTD without affecting that of long-term potentiation in the insular cortex. The disruption of ASIC1a also attenuated the extinction of established taste aversion memory without altering the initial associative taste learning or its long-term retention. Extinction of taste aversive memory led to the reduced insular synaptic efficacy, which precluded further LTD induction. The impaired LTD and extinction learning in ASIC1a null mice were restored by virus-mediated expression of wild-type ASIC1a, but not its ion-impermeable mutant, in the insular cortices. Our data demonstrate the involvement of an ASIC1a-mediated insular synaptic depression mechanism in extinction learning, which raises the possibility of targeting ASIC1a to manage adaptive behaviours. PMID:27924869

  4. Effects of Long Term Sertraline Treatment and Depression on Coronary Artery Atherosclerosis in Premenopausal Female Primates

    PubMed Central

    Shively, Carol A.; Register, Thomas C.; Appt, Susan E.; Clarkson, Thomas B.

    2015-01-01

    Objectives Major depressive disorder and coronary heart disease (CHD) often co-occur in the same individuals. Selective serotonin reuptake inhibitors (SSRIs) are widely prescribed for depression and other disorders, but their effects on CHD risk remain unclear. We determined the effects of a SSRI on coronary artery atherosclerosis (CAA) in an established nonhuman primate model used to clarify the association between depression and CAA. Methods 42 adult female cynomolgus macaques consuming a Western diet were characterized during an 18-month pretreatment phase, and assigned to SSRI (sertraline HCl 20 mg/kg, po, once/day) or Placebo balanced on pretreatment depression, body weight (BW), and iliac artery atherosclerosis extent measured via biopsy. After 18 months CAA extent was measured using histomorphometry. Results Before and during treatment depressed monkeys had lower BW, body mass index (BMI), and plasma high density lipoprotein cholesterol, and higher heart rates during the pretreatment (p<0.01) but not the treatment phase (p=0.17). There were no pretreatment differences between the sertraline and placebo groups. Sertraline reduced anxious behavior but had no effect on BW, BMI, heart rate, plasma lipids, or depression. CAA, analyzed by a 2 (Depressed, Nondepressed) × 2 (Placebo, Sertraline) × 3 (coronary arteries) analysis of covariance adjusted for pretreatment iliac atherosclerosis, was greater in depressed than nondepressed monkeys (p<0.036), and in sertraline than placebo-treated monkeys (p=0.040). The observed CAA extent in depressed monkeys treated with sertraline was 4.9 times higher than in untreated depressed monkeys, and 6.5 times higher than in non-depressed monkeys, on average. Conclusions Depressed animals develop more CAA, and that longterm treatment with sertraline promotes CAA. PMID:25829239

  5. Omega-3 polyunsaturated fatty acids enhance cerebral angiogenesis and provide long-term protection after stroke

    PubMed Central

    Wang, Jiayin; Shi, Yejie; Zhang, Lili; Zhang, Feng; Hu, Xiaoming; Zhang, Wengting; Leak, Rehana K.; Gao, Yanqin; Chen, Ling; Chen, Jun

    2014-01-01

    Stroke is a devastating neurological disorder and one of the leading causes of death and serious disability. After cerebral ischemia, revascularization in the ischemic boundary zone provides nutritive blood flow as well as various growth factors to promote the survival and activity of neurons and neural progenitor cells. Enhancement of angiogenesis and the resulting improvement of cerebral microcirculation are key restorative mechanisms and represent an important therapeutic strategy for ischemic stroke. In the present study, we tested the hypothesis that post-stroke angiogenesis would be enhanced by omega-3 polyunsaturated fatty acids (n-3 PUFAs), a major component of dietary fish oil. To this end, we found that transgenic fat-1 mice that overproduce n-3 PUFAs exhibited long-term behavioral and histological protection against transient focal cerebral ischemia (tFCI). Importantly, fat-1 transgenic mice also exhibited robust improvements in revascularization and angiogenesis compared to wild type littermates, suggesting a potential role for n-3 fatty acids in post-stroke cerebrovascular remodeling. Mechanistically, n-3 PUFAs induced upregulation of angiopoietin 2 (Ang 2) in astrocytes after tFCI and stimulated extracellular Ang 2 release from cultured astrocytes after oxygen and glucose deprivation. Ang 2 facilitated endothelial proliferation and barrier formation in vitro by potentiating the effects of VEGF on phospholipase Cγ1 and Src signaling. Consistent with these findings, blockade of Src activity in post-stroke fat-1 mice impaired n-3 PUFA-induced angiogenesis and exacerbated long-term neurological outcomes. Taken together, our findings strongly suggest that n-3 PUFA supplementation is a potential angiogenic treatment capable of augmenting brain repair and improving long-term functional recovery after cerebral ischemia. PMID:24794156

  6. Meditation with yoga, group therapy with hypnosis, and psychoeducation for long-term depressed mood: a randomized pilot trial.

    PubMed

    Butler, Lisa D; Waelde, Lynn C; Hastings, T Andrew; Chen, Xin-Hua; Symons, Barbara; Marshall, Jonathan; Kaufman, Adam; Nagy, Thomas F; Blasey, Christine M; Seibert, Elizabeth O; Spiegel, David

    2008-07-01

    This randomized pilot study investigated the effects of meditation with yoga (and psychoeducation) versus group therapy with hypnosis (and psychoeducation) versus psychoeducation alone on diagnostic status and symptom levels among 46 individuals with long-term depressive disorders. Results indicate that significantly more meditation group participants experienced a remission than did controls at 9-month follow-up. Eight hypnosis group participants also experienced a remission, but the difference from controls was not statistically significant. Three control participants, but no meditation or hypnosis participants, developed a new depressive episode during the study, though this difference did not reach statistical significance in any case. Although all groups reported some reduction in symptom levels, they did not differ significantly in that outcome. Overall, these results suggest that these two interventions show promise for treating low- to moderate-level depression.

  7. Untreated depression during pregnancy: Short- and long-term effects in offspring. A systematic review.

    PubMed

    Gentile, S

    2017-02-07

    Aim of this systematic review is to assess short- and long-lasting effects of antenatal exposure to untreated maternal depressive symptoms. Pertinent articles were identified through combined searches of Science.gov, Cochrane library, and PubMed databases (through August 2015). Forty-three, selected articles revealed that untreated gestational depression and even depressive symptoms during pregnancy may have untoward effects on the developing fetus (hyperactivity, irregular fetal heart rate), newborns (increased cortisol and norepinephrine levels, decreased dopamine levels, altered EEG patterns, reduced vagal tone, stress/depressive-like behaviors, and increased rates of premature deaths and neonatal intensive care unit admission), and children (increased salivary cortisol levels, internalizing and externalizing problems, and central adiposity). During adolescence, an independent association exists between maternal antenatal mood symptoms and a slight increase in criminal behaviors. In contrast, the relationship between gestational depression and increased risks of prematurity and low birth weight remains controversial. Given this background, when making clinical decisions, clinicians should weigh the growing evidences suggesting the detrimental and prolonged effects in offspring of untreated antenatal depression and depressive symptoms during pregnancy against the known and emerging concerns associated with in utero exposure to antidepressants.

  8. Long Term, Operational Monitoring Of Enhanced Oil Recovery In Harsh Environments With INSAR

    NASA Astrophysics Data System (ADS)

    Sato, S.; Henschel, M. D.

    2012-01-01

    Since 2004, MDA GSI has provided ground deformation measurements for an oil field in northern Alberta, Canada using InSAR technology. During this period, the monitoring has reliably shown the slow rise of the oil field due to enhanced oil recovery operations. The InSAR monitoring solution is essentially based on the observation of point and point-like targets in the field. Ground conditions in the area are almost continuously changing (in their reflectivity characteristics) making it difficult to ob- serve coherent patterns from the ground. The extended duration of the oil operations has allowed us to continue InSAR monitoring and transition from RADARSAT-1 to RADARSAT-2. With RADARSAT-2 and the enhancement of the satellite resolution capability has provided more targets of opportunity as identified by a differential coherence method. This poster provides an overview of the long term monitoring of the oil field in northern Alberta, Canada.

  9. Enhanced long-term recollection for emotional pictures: evidence from high-density ERPs.

    PubMed

    Weymar, Mathias; Löw, Andreas; Melzig, Christiane A; Hamm, Alfons O

    2009-11-01

    The present study used behavioral and electrophysiological measures to investigate the processes mediating long-term recognition memory for emotional and neutral pictures. The results show enhanced memory recollection for emotional arousing pictures compared to neutral low arousing pictures. In accordance with the behavioral data, we observed enhanced old/new effects in the ERPs for emotionally arousing pictures in the recollection-sensitive old/new component at centro-parietal sites (500-800 ms). Moreover, early old/new effects were present over frontal and parietal sites (300-500 ms) irrespective of picture contents. Analysis of the subjective awareness, indexed by the confidence ratings, showed that the late parietal old/new effect was increased for high confidence responses whereas the early component (300-500 ms) was mainly driven by low confidence responses, an indication for familiarity based recognition processes.

  10. Postsynaptic production of nitric oxide implicated in long-term depression at the mature amphibian (Bufo marinus) neuromuscular junction

    PubMed Central

    Etherington, Sarah J; Everett, Alan W

    2004-01-01

    We report here evidence for endogenous NO signalling in long-term (> 1 h) synaptic depression at the neuromuscular junction induced by 20 min of 1 Hz nerve stimulation. Synaptic depression was characterized by a 46% reduction in the end-plate potential (EPP) amplitude and a 21% decrease in miniature EPP (MEPP) frequency, but no change to MEPP amplitude, indicating a reduction in evoked quantal release. Both the membrane-impermeant NO scavenger cPTIO and the NOS inhibitor+ release from the sarcoplasmic reticulum and muscle contraction were blocked with dantrolene. These data suggest that the depression depends on transmission, but not muscle contraction. The calcineurin inhibitors cyclosporin A and FK506, as well as ODQ, an inhibitor of NO-sensitive soluble guanylyl cyclase, Rp-8-pCPT-cGMPS, an inhibitor of cGMP-dependent protein kinase, and the calmodulin antagonist phenoxybenzamine also blocked depression. We propose that low frequency synaptic transmission leads to production of NO at the synapse and depression of transmitter release via a cGMP-dependent mechanism. The NO could be generated either directly from the muscle, or possibly from the Schwann cell in response to an unidentified muscle-derived messenger. We showed that the long-lasting depression of transmitter release was due to sustained activity of the NO signalling pathway, and suggest dephosphorylation of NOS by calcineurin as the basis for continued NO production. PMID:15243135

  11. Acute and long-term effectiveness of clozapine in treatment-resistant psychotic depression.

    PubMed

    Ranjan, R; Meltzer, H Y

    1996-08-15

    The treatment of refractory major depression, including the psychotic subtype, is a therapeutic challenge. Three cases of resistant psychotic depression were treated with clozapine monotherapy, an atypical antipsychotic drug effective in treatment-resistant schizophrenia and mania. Both psychotic and mood symptoms responded well to clozapine monotherapy, although response was delayed in one case. Tardive dyskinesia improved markedly, and tardive dystonia improved moderately in one patient. No patient relapsed during a follow-up period of 4-6 years of clozapine treatment. Clozapine was well-tolerated with few side effects. These observations suggest controlled trials of clozapine in the treatment of psychotic depression that fails to respond to electroconvulsive therapy or typical neuroleptics plus tricyclic antidepressants are indicated. The same is true for the use of clozapine in maintenance treatment for psychotic depression in those cases in which typical neuroleptic drugs are required, in order to reduce the risk of tardive dyskinesia and dystonia.

  12. DHHC8-dependent PICK1 palmitoylation is required for induction of cerebellar long-term synaptic depression.

    PubMed

    Thomas, Gareth M; Hayashi, Takashi; Huganir, Richard L; Linden, David J

    2013-09-25

    The palmitoyl acyltransferase (PAT) DHHC8 is implicated in synaptic regulation but few DHHC8 substrates are known. Here we report that DHHC8 binds and palmitoylates the PDZ domain-containing protein PICK1 at a cysteine residue that is essential for long-term synaptic depression (LTD) in cultured mouse cerebellar Purkinje neurons. Cerebellar LTD is palmitoylation-dependent and induction of LTD requires DHHC8. Furthermore, PICK1 is a critical DHHC8 substrate whose palmitoylation is necessary for LTD. These results identify the first DHHC8 substrate required for a specific form of synaptic plasticity and provide new insights into synaptic roles of palmitoylation.

  13. Brain activation patterns in major depressive disorder and work stress-related long-term sick leave among Swedish females.

    PubMed

    Sandström, Agneta; Säll, Roland; Peterson, Jonas; Salami, Alireza; Larsson, Anne; Olsson, Tommy; Nyberg, Lars

    2012-09-01

    Deficits in executive functioning and working memory associated with frontal lobe dysfunction are prominent in depression and work-related long-term sick leave (LTSL). This study used functional magnetic resonance imaging (fMRI) to investigate potential differences in brain activation patterns in these conditions. In addition, the function of the hypothalamic-pituitary-adrenal (HPA) axis was examined and compared between groups. Since there is a clear overrepresentation of women in these diagnostic groups, and to ensure a more homogenous sample population, only women were included. To examine the neural correlates of relevant cognitive processes in patients on sick leave >90 days due to work-related LTSL, recently diagnosed patients with major depression Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV criteria, untreated), and healthy controls (n = 10, each group), a 2-back working memory task and a visual long-term memory task were administered during fMRI scanning. HPA axis functioning was investigated using a diurnal curve of saliva cortisol and a dexamethasone suppression test. Task performance was comparable among the three groups. Multivariate image analysis revealed that both memory tasks engaged a similar brain network in all three groups, including the prefrontal and parietal cortex. During the 2-back task, LTSL patients had significant frontal hypoactivation compared to controls and patients with depression. Saliva cortisol measurements showed a flattening of the diurnal rythmicity in LTSL patients compared to patients with depression and healthy contols. Taken together, these findings indicate that work stress-related LTSL and major depression are dissociable in terms of frontal activation and diurnal cortisol rhythmicity.

  14. Assessment of different induction protocols to elicit long-term depression (LTD) in the rat visual cortex in vivo.

    PubMed

    Hager, Audrey M; Dringenberg, Hans C

    2010-03-08

    Changes in synaptic efficacy, including long-term potentiation (LTP) and long-term depression (LTD), provide mechanisms for experience-induced plasticity of cortical and subcortical circuits. LTP is readily induced under drastically different experimental conditions (e.g., in vitro and in vivo). However, few studies have compared the effectiveness of different induction protocols to elicit synaptic depression, especially under in vivo conditions. Here, we assessed the effectiveness of four different low frequency stimulation (LFS) protocols, applied to the lateral geniculate nucleus, to induce LTD-like changes of local field postsynaptic potentials (fPSPs) recorded on the surface of the primary visual cortex (V1) of urethane-anesthetized rats. Three LFS protocols (900 pulses at 1 Hz; 1800 pulses at 1 Hz, 1800 pulses at 1 Hz, repeated three times), known to induce LTD in neocortical and hippocampal slice preparations, failed to induce synaptic depression. In contrast, strong low frequency burst stimulation (3 pulses/burst at 20 Hz, 900 bursts repeated at 1 Hz) resulted in significant, but transient ( approximately 20 min) depression of fPSPs in V1. This effect was resistant to systemic treatment with MK 801 (0.5 mg/kg) or local, cortical application of either APV (10 mM) or MCPG (10 mM), indicative of non-essential roles of N-methyl-d-aspartate and metabotropic glutamate receptors. A similar depressant effect was also observed under sodium pentobarbital anesthesia. These experiments emphasize the resistance of the in vivo neocortex to express the long-lasting down-regulation of synaptic strength, observations that require integration into current models and theories regarding the functions of LTD as a homeostatic and experience-dependent plasticity mechanism.

  15. Symptomatic depression after long-term steroid treatment: a case report.

    PubMed

    Ros, Leszek Tomasz

    2004-09-01

    Good results of the treatment of mood disturbances and psychoses induced with steroid administration are in agreement with the fact described in literature of serotonin release reduction caused by steroids and possible relationship between depressive and psychotic manifestations and low seretonin level in cerebrospinal fluid. The patient had no head trauma in the past. He denied any loss of consciousness. The patient at the age of six years had type C virus hepatitis which changed into chronic hepatitis with a slight autoimmune component. He received six months oral steroid (prednisone) treatment in 20 mg daily dose resulting in symptomatic depression. The patient was treated by the author with sertraline from low doses up to 150 mg daily. A remission of the depressive illness and OCD was obtained. The author decided to treat the patient with sertraline in view of its high safety in somatic diseases and good tolerance.

  16. 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

  17. The Long-Term Effects of War Experiences on Children's Depression in the Republic of Croatia

    ERIC Educational Resources Information Center

    Brajsa-Zganec, A.

    2005-01-01

    Objective:: The aim of the study was to investigate whether different levels of depressive symptoms in early adolescent boys and girls could be predicted on the basis of war experiences, perceived available social support (instrumental support, support to self-esteem, belonging and acceptance) and extraversion. Methods:: The sample consisted of…

  18. Therapist-Assisted, Self-Administered Bibliotherapy to Enhance Parental Competence: Short- and Long-Term Effects

    ERIC Educational Resources Information Center

    Hahlweg, Kurt; Heinrichs, Nina; Kuschel, Annett; Feldmann, Marit

    2008-01-01

    The efficacy of bibliotherapy has primarily been investigated in anxiety disorders, depression, or substance dependence. The efficacy of self-help books to increase parenting competence was only investigated in a few studies despite their broad dissemination in public. The aims of the study were to investigate the short- and long-term efficacy of…

  19. Long-term growth enhancement of baldcypress (Taxodium distichum) from municipal wastewater application

    USGS Publications Warehouse

    Hesse, I.D.; Day, J.W.; Doyle, T.W.

    1998-01-01

    Tree ring analysis was used to document the long-term effects of municipal wastewater on the growth rate of baldcypress (Taxodium distichum (L.) Rich.]. The study site, a swamp in St. Martin Parish, Louisiana, has received municipal wastewater for the last 40 years. Growth chronologies from 1920 to 1992 were developed from cross-dated tree core samples taken from treated and control sites with similar size and age classes. Mean diameter increment (DINC) and mean basal area increment (BAI) chronologies were constructed separately for each stand. These chronologies were then summarized by tree and stand into seven nine-year intervals resulting in three pretreatment intervals from 1926 to 1952 and four treatment intervals from 1953 to 1988. Significant differences in growth response between sites showed a consistent pattern of growth enhancement in the treated site coincident with the onset of effluent discharge. The ratio of treated to control baldcypress growth rates (computed from DINC) averaged 0.74 during the pretreatment period and 1.53 during the treatment period. Over the period of study, control DINC decreased from 77 mm to 29 mm/nine-year interval, while treatment DINC increased slightly from 40 mm to 47 mm/nine-year interval. Control BAI did not increase significantly and averaged 192 cm2/nine-year interval. There was a significant increase in treatment BAI from 129 to 333 cm2/nine-year interval over the period of record. These results clearly demonstrate sustained long-term baldcypress growth enhancement throughout 40 years of municipal effluent discharge.

  20. Primary Blast Injury Depressed Hippocampal Long-Term Potentiation through Disruption of Synaptic Proteins.

    PubMed

    Vogel, Edward W; Rwema, Steve H; Meaney, David F; Bass, Cameron R Dale; Morrison, Barclay

    2017-03-01

    Blast-induced traumatic brain injury (bTBI) is a major threat to United States service members in military conflicts worldwide. The effects of primary blast, caused by the supersonic shockwave interacting with the skull and brain, remain unclear. Our group has previously reported that in vitro primary blast exposure can reduce long-term potentiation (LTP), the electrophysiological correlate of learning and memory, in rat organotypic hippocampal slice cultures (OHSCs) without significant changes to cell viability or basal, evoked neuronal function. We investigated the time course of primary blast-induced deficits in LTP and the molecular mechanisms that could underlie these deficits. We found that pure primary blast exposure induced LTP deficits in a delayed manner, requiring longer than 1 hour to develop, and that these deficits spontaneously recovered by 10 days following exposure depending on blast intensity. Additionally, we observed that primary blast exposure reduced total α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) glutamate receptor 1 (GluR1) subunit expression and phosphorylation of the GluR1 subunit at the serine-831 site. Blast also reduced the expression of postsynaptic density protein-95 (PSD-95) and phosphorylation of stargazin protein at the serine-239/240 site. Finally, we found that modulation of the cyclic adenosine monophosphate (cAMP) pathway ameliorated electrophysiological and protein-expression changes caused by blast. These findings could inform the development of novel therapies to treat blast-induced loss of neuronal function.

  1. Long-Term Symptoms of Depression and Anxiety in Mothers of Infants with Congenital Heart Defects

    PubMed Central

    Grønning Dale, Maria T.; Holmstrøm, Henrik; Eskedal, Leif T.; Landolt, Markus A.; Vollrath, Margarete E.

    2011-01-01

    Objective To examine the relationship between the severity of infants’ congenital heart defects (CHD) and their mothers’ symptoms of depression and anxiety from pregnancy to 18 months postpartum. Methods Mothers of infants with mild, moderate, or severe CHD (n = 162) and mothers (n = 44 400) within the Norwegian Mother and Child Cohort Study were assessed with an eight-item short version (SCL-8) of the Hopkins Symptom Checklist-25 at the 30th week of gestation and at 6 and 18 months postpartum. Results Only the postpartum mental health trajectory of mothers of infants with severe CHD deviated from the mental health trajectory of the cohort at 6 and 18 months postpartum, showing significantly elevated levels of depression and anxiety symptoms. Conclusions The results elucidate the relationship between infants’ CHD severity and maternal symptoms of depression and anxiety, possibly identifying a specifically vulnerable patient dyad in need of postoperative interventions. PMID:20558484

  2. Enhancing the retrieval methodology for GlobSnow long-term snow water equivalent record

    NASA Astrophysics Data System (ADS)

    Luojus, K.; Pulliainen, J.; Lemmetyinen, J.; Takala, M.; Smolander, T.; Derksen, C.

    2012-04-01

    The efforts of the European Space Agency (ESA) GlobSnow project has resulted in a daily hemisphere-scale satellite-based snow water equivalent (SWE) data record spanning more than 30-years. The previous existing daily SWE records have spanned a shorter time period or described the snow conditions on a monthly basis for a similar period. The GlobSnow SWE record, based on methodology by Pulliainen [1] utilizes a data-assimilation based approach for the estimation of SWE which was shown to be superior to the approaches depending solely on satellite-based data [2]. The GlobSnow SWE data record is based on the time-series of measurements by two different space-borne passive radiometers (SMMR and SSM/I) measuring in the microwave region, spanning from 1979 to present day. The utilized sensors provide data at K- and Ka-bands (19 GHz and 37 GHz respectively) at a spatial resolution of approximately 25 km. The GlobSnow SWE data record has been released and is available through the GlobSnow web-pages (www.globsnow.info). We briefly presents the validation carried out for GlobSnow SWE data with ground-based reference data and the lessons learned from processing a 30-years daily hemispheric record on SWE. Additionally, we present the efforts taking place for the continuous development of the methodology to enhance the satellite-based SWE retrieval and the way this transfers to the reliability of the long-term SWE climate record. The development of SWE retrieval are focused on application of a new HUT multi-layer snow emission model for the retrieval procedure, application of novel techniques to account for lake contamination and mixed pixel effects and efforts carried out to create a homogenized long-term record of weather station-based snow depth observations that are applied within the SWE retrieval scheme.

  3. Appetitive long-term taste conditioning enhances human visually evoked EEG responses.

    PubMed

    Viemose, Ida; Møller, Per; Laugesen, Jakob L; Schachtman, Todd R; Manoharan, Thukirtha; Christoffersen, Gert R J

    2013-09-15

    Long-term effects of learned associations between an image and a taste have not been studied with electromagnetic brain scanning techniques. The possibility that taste conditioning may change sensory image processing was investigated in young adult subjects. EEG-responses evoked by images were recorded before and after a training session using an image as conditioned stimulus and a pleasant taste as unconditioned stimulus. The results showed that in posterior electrodes placed over visual cortex areas, the following changes occurred after conditioning: (1) the amplitude and duration of the N2-P3 waves in the visual evoked potentials were enhanced; (2) the N2 and P3 peak delays were shortened; (3) power induced by image presentation was enhanced in the delta and theta frequency bands; (4) cross-hemispheric delta and theta coherences among the posterior electrodes were enhanced; (5) calculations of the underlying whole brain distribution of currents using swLORETA showed elevated current densities in posterior voxels. None of the above changes occurred in a sham-trained control group. In electrodes placed over the prefrontal cortex, delta and theta power also rose significantly. It is suggested that the appetitive taste conditioning potentiated synaptic activity in visual cortex networks and that this led to an increased speed of image processing.

  4. Longitudinal Changes in Psychological States in Online Health Community Members: Understanding the Long-Term Effects of Participating in an Online Depression Community

    PubMed Central

    Conway, Mike

    2017-01-01

    emotion-related language usage of depression community members are improving either significantly or at least as much as members of other online communities. On the basis of these findings, we contribute practical suggestions for designing online depression communities to enhance psychosocial benefit gains for members. We consider these results to be an important step toward a better understanding of the impact of prolonged participation in an online depression community, in addition to providing insights into the long-term psychosocial well-being of members. PMID:28320692

  5. Alteration in plasma corticosterone levels following long term oral administration of lead produces depression like symptoms in rats.

    PubMed

    Haider, Saida; Saleem, Sadia; Tabassum, Saiqa; Khaliq, Saima; Shamim, Saima; Batool, Zehra; Parveen, Tahira; Inam, Qurat-ul-ain; Haleem, Darakhshan J

    2013-03-01

    Lead toxicity is known to induce a broad range of physiological, biochemical and behavioral dysfunctions that may result in adverse effects on several organs, including the central nervous system. Long-term exposure to low levels of lead (Pb(2+)) has been shown to produce behavioral deficits in rodents and humans by affecting hypothalamic-pituitary-adrenal (HPA) axis. These deficits are thought to be associated with altered brain monoamine neurotransmission and due to changes in glucocorticoids levels. This study was designed to investigate the effects of Pb(2+)exposure on growth rate, locomotor activity, anxiety, depression, plasma corticosterone and brain serotonin (5-HT) levels in rats. Rats were exposed to lead in drinking water (500 ppm; lead acetate) for 5 weeks. The assessment of depression was done using the forced swimming test (FST). Estimation of brain 5-HT was determined by high-performance liquid chromatography with electrochemical detection. Plasma corticosterone was determined by spectrofluorimetric method. The present study showed that long term exposure to Pb(2+) significantly decreased the food intake followed by the decrease in growth rate in Pb(2+)exposed rats as compared to control group. No significant changes in open field activity were observed following Pb(2+)exposure while significant increase in anxiogenic effect was observed. Increased plasma corticosterone and decreased 5-HT levels were exhibited by Pb(2+)exposed rats as compared to controls. A significant increase in depressive like symptoms was exhibited by Pb(2+)exposed rats as compared to control rats. The results are discussed in the context of Pb(2+) inducing a stress-like response in rats leading to changes in plasma corticosterone and brain 5-HT levels via altering tryptophan pyrrolase activity.

  6. Exchange Protein Activated by cAMP Enhances Long-Term Memory Formation Independent of Protein Kinase A

    ERIC Educational Resources Information Center

    Ma, Nan; Abel, Ted; Hernandez, Pepe J.

    2009-01-01

    It is well established that cAMP signaling within neurons plays a major role in the formation of long-term memories--signaling thought to proceed through protein kinase A (PKA). However, here we show that exchange protein activated by cAMP (Epac) is able to enhance the formation of long-term memory in the hippocampus and appears to do so…

  7. Short- and long-term depression at glutamatergic synapses on hippocampal interneurons by group I mGluR activation.

    PubMed

    Le Duigou, Caroline; Holden, Thomas; Kullmann, Dimitri M

    2011-04-01

    Group I metabotropic glutamate receptors (mGluRs) are expressed by many interneurons of the hippocampus. Although they have been implicated in short- and long-term synaptic plasticity of glutamatergic transmission, their roles in modulating transmission to interneurons are incompletely understood. The selective group I mGluR agonist (S)-3,5-dihydroxyphenylglycine (DHPG) acutely depressed transmission at synapses in the feed-forward inhibitory pathway made by Schaffer collaterals on interneurons in the rat hippocampal CA1 sub-field. DHPG elicited a qualitatively similar depression at synapses made by pyramidal neuron axon collaterals on interneurons in the feedback circuit in stratum oriens. Selective blockers revealed a link from mGluR1 to reversible, and mGluR5 to long-lasting, depression. The acute DHPG-induced depression was consistently accompanied by an elevation in paired-pulse ratio, implying a presynaptic decrease in release probability. However, it was also attenuated by blocking G-protein and Ca(2+) signalling within the postsynaptic neuron, arguing for a retrograde signalling cascade. The DHPG-evoked depression was unaffected by antagonists of CB1 and GABA(B) receptors but was occluded when presynaptic P/Q-type Ca(2+) channels were blocked. Finally, high-frequency stimulation delivered to an independent conditioning pathway evoked a heterosynaptic reversible depression, which was sensitive to group I mGluR antagonists. Group I mGluRs thus powerfully modulate synaptic excitation of hippocampal interneurons and mediate inter-synaptic cross-talk. This article is part of a Special Issue entitled 'Synaptic Plasticity & Interneurons'.

  8. Long-term academic stress enhances early processing of facial expressions.

    PubMed

    Zhang, Liang; Qin, Shaozheng; Yao, Zhuxi; Zhang, Kan; Wu, Jianhui

    2016-11-01

    Exposure to long-term stress can lead to a variety of emotional and behavioral problems. Although widely investigated, the neural basis of how long-term stress impacts emotional processing in humans remains largely elusive. Using event-related brain potentials (ERPs), we investigated the effects of long-term stress on the neural dynamics of emotionally facial expression processing. Thirty-nine male college students undergoing preparation for a major examination and twenty-one matched controls performed a gender discrimination task for faces displaying angry, happy, and neutral expressions. The results of the Perceived Stress Scale showed that participants in the stress group perceived higher levels of long-term stress relative to the control group. ERP analyses revealed differential effects of long-term stress on two early stages of facial expression processing: 1) long-term stress generally augmented posterior P1 amplitudes to facial stimuli irrespective of expression valence, suggesting that stress can increase sensitization to visual inputs in general, and 2) long-term stress selectively augmented fronto-central P2 amplitudes for angry but not for neutral or positive facial expressions, suggesting that stress may lead to increased attentional prioritization to processing negative emotional stimuli. Together, our findings suggest that long-term stress has profound impacts on the early stages of facial expression processing, with an increase at the very early stage of general information inputs and a subsequent attentional bias toward processing emotionally negative stimuli.

  9. Serum from humans on long-term calorie restriction enhances stress resistance in cell culture

    PubMed Central

    Salvatore, Francesco; Crosby, Seth D.; Fontana, Luigi

    2013-01-01

    Calorie restriction (CR) without malnutrition is the most robust intervention to slow aging and extend healthy lifespan in experimental model organisms. Several metabolic and molecular adaptations have been hypothesized to play a role in mediating the anti-aging effects of CR, including enhanced stress resistance, reduced oxidative stress and several neuroendocrine modifications. However, little is known about the independent effect of circulating factors in modulating key molecular pathways. In this study, we used sera collected from individuals practicing long-term CR and from age- and sex-matched individuals on a typical US diet to culture human primary fibroblasts and assess the effects on gene expression and stress resistance. We show that treatment of cultured cells with CR sera caused increased expression of stress-response genes and enhanced tolerance to oxidants. Cells cultured in serum from CR individuals showed a 30% increase in resistance to H2O2 damage. Consistently, SOD2 and GPX1 mRNA, two key endogenous antioxidant enzymes, were increased by 2 and 2.5 folds respectively in cells cultured with CR sera. These cellular and molecular adaptations mirror some of the key effects of CR in animals, and further suggest that circulating factors contribute to the CR-mediated protection against oxidative stress and stress-response in humans as well. PMID:23912304

  10. GABAergic Activities Control Spike Timing- and Frequency-Dependent Long-Term Depression at Hippocampal Excitatory Synapses

    PubMed Central

    Nishiyama, Makoto; Togashi, Kazunobu; Aihara, Takeshi; Hong, Kyonsoo

    2010-01-01

    GABAergic interneuronal network activities in the hippocampus control a variety of neural functions, including learning and memory, by regulating θ and γ oscillations. How these GABAergic activities at pre- and postsynaptic sites of hippocampal CA1 pyramidal cells differentially contribute to synaptic function and plasticity during their repetitive pre- and postsynaptic spiking at θ and γ oscillations is largely unknown. We show here that activities mediated by postsynaptic GABAARs and presynaptic GABABRs determine, respectively, the spike timing- and frequency-dependence of activity-induced synaptic modifications at Schaffer collateral-CA1 excitatory synapses. We demonstrate that both feedforward and feedback GABAAR-mediated inhibition in the postsynaptic cell controls the spike timing-dependent long-term depression of excitatory inputs (“e-LTD”) at the θ frequency. We also show that feedback postsynaptic inhibition specifically causes e-LTD of inputs that induce small postsynaptic currents (<70 pA) with LTP-timing, thus enforcing the requirement of cooperativity for induction of long-term potentiation at excitatory inputs (“e-LTP”). Furthermore, under spike-timing protocols that induce e-LTP and e-LTD at excitatory synapses, we observed parallel induction of LTP and LTD at inhibitory inputs (“i-LTP” and “i-LTD”) to the same postsynaptic cells. Finally, we show that presynaptic GABABR-mediated inhibition plays a major role in the induction of frequency-dependent e-LTD at α and β frequencies. These observations demonstrate the critical influence of GABAergic interneuronal network activities in regulating the spike timing- and frequency-dependences of long-term synaptic modifications in the hippocampus. PMID:21423508

  11. Animal model of methylphenidate's long-term memory-enhancing effects.

    PubMed

    Carmack, Stephanie A; Howell, Kristin K; Rasaei, Kleou; Reas, Emilie T; Anagnostaras, Stephan G

    2014-01-16

    Methylphenidate (MPH), introduced more than 60 years ago, accounts for two-thirds of current prescriptions for attention deficit hyperactivity disorder (ADHD). Although many studies have modeled MPH's effect on executive function, almost none have directly modeled its effect on long-term memory (LTM), even though improvement in LTM is a critical target of therapeutic intervention in ADHD. We examined the effects of a wide range of doses of MPH (0.01-10 mg/kg, i.p.) on Pavlovian fear learning, a leading model of memory. MPH's effects were then compared to those of atomoxetine (0.1-10 mg/kg, i.p.), bupropion (0.5-20 mg/kg, i.p.), and citalopram (0.01-10 mg/kg, i.p.). At low, clinically relevant doses, MPH enhanced fear memory; at high doses it impaired memory. MPH's memory-enhancing effects were not confounded by its effects on locomotion or anxiety. Further, MPH-induced memory enhancement seemed to require both dopamine and norepinephrine transporter inhibition. Finally, the addictive potential of MPH (1 mg/kg and 10 mg/kg) was compared to those of two other psychostimulants, amphetamine (0.005 mg/kg and 1.5 mg/kg) and cocaine (0.15 mg/kg and 15 mg/kg), using a conditioned place preference and behavioral sensitization paradigm. We found that memory-enhancing effects of psychostimulants observed at low doses are readily dissociable from their reinforcing and locomotor activating effects at high doses. Together, our data suggest that fear conditioning will be an especially fruitful platform for modeling the effects of psychostimulants on LTM in drug development.

  12. Animal model of methylphenidate's long-term memory-enhancing effects

    PubMed Central

    Carmack, Stephanie A.; Howell, Kristin K.; Rasaei, Kleou; Reas, Emilie T.; Anagnostaras, Stephan G.

    2014-01-01

    Methylphenidate (MPH), introduced more than 60 years ago, accounts for two-thirds of current prescriptions for attention deficit hyperactivity disorder (ADHD). Although many studies have modeled MPH's effect on executive function, almost none have directly modeled its effect on long-term memory (LTM), even though improvement in LTM is a critical target of therapeutic intervention in ADHD. We examined the effects of a wide range of doses of MPH (0.01–10 mg/kg, i.p.) on Pavlovian fear learning, a leading model of memory. MPH's effects were then compared to those of atomoxetine (0.1–10 mg/kg, i.p.), bupropion (0.5–20 mg/kg, i.p.), and citalopram (0.01–10 mg/kg, i.p.). At low, clinically relevant doses, MPH enhanced fear memory; at high doses it impaired memory. MPH's memory-enhancing effects were not confounded by its effects on locomotion or anxiety. Further, MPH-induced memory enhancement seemed to require both dopamine and norepinephrine transporter inhibition. Finally, the addictive potential of MPH (1 mg/kg and 10 mg/kg) was compared to those of two other psychostimulants, amphetamine (0.005 mg/kg and 1.5 mg/kg) and cocaine (0.15 mg/kg and 15 mg/kg), using a conditioned place preference and behavioral sensitization paradigm. We found that memory-enhancing effects of psychostimulants observed at low doses are readily dissociable from their reinforcing and locomotor activating effects at high doses. Together, our data suggest that fear conditioning will be an especially fruitful platform for modeling the effects of psychostimulants on LTM in drug development. PMID:24434869

  13. Robustness of retrieval properties against imbalance between long-term potentiation and depression of spike-timing-dependent plasticity

    NASA Astrophysics Data System (ADS)

    Matsumoto, Narihisa; Okada, Masato

    2003-12-01

    Spike-timing-dependent plasticity (STDP) has recently been shown in some physiological studies. STDP depends on the precise temporal relationship of presynaptic and postsynaptic spikes. Many authors have indicated that a precise balance between long-term potentiation (LTP) and long-term depression (LTD) of STDP is significant for a stable learning. However, a situation in which the balance is maintained precisely is inconceivable in the brain. Using a method of the statistical neurodynamics, we show robust retrieval properties of spatiotemporal patterns in an associative memory model against the imbalance between LTP and LTD. When the fluctuation of LTD is assumed to obey a Gaussian distribution with mean 0 and variance δ2, the storage capacity takes a finite value even at large δ. This means that the balance between LTP and LTD of STDP need not be maintained precisely, but must be maintained on average. Furthermore, we found that the basin of attraction becomes smaller as δ increases while an initial critical overlap remains unchanged.

  14. Mild Concussion, but Not Moderate Traumatic Brain Injury, Is Associated with Long-Term Depression-Like Phenotype in Mice.

    PubMed

    Bajwa, Nikita M; Halavi, Shina; Hamer, Mary; Semple, Bridgette D; Noble-Haeusslein, Linda J; Baghchechi, Mohsen; Hiroto, Alex; Hartman, Richard E; Obenaus, André

    2016-01-01

    Mild traumatic brain injuries can lead to long-lasting cognitive and motor deficits, increasing the risk of future behavioral, neurological, and affective disorders. Our study focused on long-term behavioral deficits after repeated injury in which mice received either a single mild CHI (mCHI), a repeated mild CHI (rmCHI) consisting of one impact to each hemisphere separated by 3 days, or a moderate controlled cortical impact injury (CCI). Shams received only anesthesia. Behavioral tests were administered at 1, 3, 5, 7, and 90 days post-injury (dpi). CCI animals showed significant motor and sensory deficits in the early (1-7 dpi) and long-term (90 dpi) stages of testing. Interestingly, sensory and subtle motor deficits in rmCHI animals were found at 90 dpi. Most importantly, depression-like behaviors and social passiveness were observed in rmCHI animals at 90 dpi. These data suggest that mild concussive injuries lead to motor and sensory deficits and affective disorders that are not observed after moderate TBI.

  15. Effect of the Initial Synaptic State on the Probability to Induce Long-Term Potentiation and Depression

    PubMed Central

    Migliore, Michele; De Simone, Giada; Migliore, Rosanna

    2015-01-01

    Long-term potentiation (LTP) and long-term depression (LTD) are the two major forms of long-lasting synaptic plasticity in the mammalian neurons, and are directly related to higher brain functions such as learning and memory. Experimentally, they are characterized by a change in the strength of a synaptic connection induced by repetitive and properly patterned stimulation protocols. Although many important details of the molecular events leading to LTP and LTD are known, experimenters often report problems in using standard induction protocols to obtain consistent results, especially for LTD in vivo. We hypothesize that a possible source of confusion in interpreting the results, from any given experiment on synaptic plasticity, can be the intrinsic limitation of the experimental techniques, which cannot take into account the actual state and peak conductance of the synapses before the conditioning protocol. In this article, we investigate the possibility that the same experimental protocol may result in different consequences (e.g., LTD instead of LTP), according to the initial conditions of the stimulated synapses, and can generate confusing results. Using biophysical models of synaptic plasticity and hippocampal CA1 pyramidal neurons, we study how, why, and to what extent the phenomena observed at the soma after induction of LTP/LTD reflects the actual (local) synaptic state. The model and the results suggest a physiologically plausible explanation for why LTD induction is experimentally difficult to obtain. They also suggest experimentally testable predictions on the stimulation protocols that may be more effective. PMID:25762316

  16. Hampered long-term depression and thin spine loss in the nucleus accumbens of ethanol-dependent rats.

    PubMed

    Spiga, Saturnino; Talani, Giuseppe; Mulas, Giovanna; Licheri, Valentina; Fois, Giulia R; Muggironi, Giulia; Masala, Nicola; Cannizzaro, Carla; Biggio, Giovanni; Sanna, Enrico; Diana, Marco

    2014-09-02

    Alcoholism involves long-term cognitive deficits, including memory impairment, resulting in substantial cost to society. Neuronal refinement and stabilization are hypothesized to confer resilience to poor decision making and addictive-like behaviors, such as excessive ethanol drinking and dependence. Accordingly, structural abnormalities are likely to contribute to synaptic dysfunctions that occur from suddenly ceasing the use of alcohol after chronic ingestion. Here we show that ethanol-dependent rats display a loss of dendritic spines in medium spiny neurons of the nucleus accumbens (Nacc) shell, accompanied by a reduction of tyrosine hydroxylase immunostaining and postsynaptic density 95-positive elements. Further analysis indicates that "long thin" but not "mushroom" spines are selectively affected. In addition, patch-clamp experiments from Nacc slices reveal that long-term depression (LTD) formation is hampered, with parallel changes in field potential recordings and reductions in NMDA-mediated synaptic currents. These changes are restricted to the withdrawal phase of ethanol dependence, suggesting their relevance in the genesis of signs and/or symptoms affecting ethanol withdrawal and thus the whole addictive cycle. Overall, these results highlight the key role of dynamic alterations in dendritic spines and their presynaptic afferents in the evolution of alcohol dependence. Furthermore, they suggest that the selective loss of long thin spines together with a reduced NMDA receptor function may affect learning. Disruption of this LTD could contribute to the rigid emotional and motivational state observed in alcohol dependence.

  17. Effect of long-term caffeine administration on depressive-like behavior in rats exposed to chronic unpredictable stress.

    PubMed

    Pechlivanova, Daniela M; Tchekalarova, Jana D; Alova, Liana H; Petkov, Vesselin V; Nikolov, Rumen P; Yakimova, Krassimira S

    2012-08-01

    Chronic unpredictable stress (CUS) was used to study the effects of a long-term treatment with either caffeine (8 mg/kg, orally) or desipramine (DMI) (10 mg/kg, intraperitoneally) in Wistar rats. The CUS procedure was applied for 6 weeks. Animals underwent a 2-week drug-free CUS procedure. Drugs were administered for 4 weeks alongside the stress and both drug and stress were continued throughout the behavioral testing period. CUS-exposed rats showed depressive-like behavior with reduced weight gain, reduced consumption of sucrose solution, increased immobility in the forced swimming test, and hypolocomotion in an open field. For the open field and elevated plus maze, calculation of an anxiety index confirmed that CUS increased anxiety, which was accompanied by an increase in the core temperature. DMI counteracted these physical and behavioral changes. Caffeine caused similar effects to DMI on weight gain, motor activity, anxiety level, and core temperature. In CUS-exposed rats, caffeine showed antidepressant and anxiolytic activity, accompanied by increased hippocampal dopamine and serotonin levels. However, no significant change in weight gain or core temperature was observed after caffeine treatment in CUS-exposed rats. These results suggest that, similar to the antidepressant DMI, long-term caffeine exposure exerts an antidepressant and anxiolytic effect in the CUS model. The involvement of the dopaminergic and serotonergic systems is discussed.

  18. Mild Concussion, but Not Moderate Traumatic Brain Injury, Is Associated with Long-Term Depression-Like Phenotype in Mice

    PubMed Central

    Hamer, Mary; Semple, Bridgette D.; Noble-Haeusslein, Linda J.; Baghchechi, Mohsen; Hiroto, Alex; Hartman, Richard E.; Obenaus, André

    2016-01-01

    Mild traumatic brain injuries can lead to long-lasting cognitive and motor deficits, increasing the risk of future behavioral, neurological, and affective disorders. Our study focused on long-term behavioral deficits after repeated injury in which mice received either a single mild CHI (mCHI), a repeated mild CHI (rmCHI) consisting of one impact to each hemisphere separated by 3 days, or a moderate controlled cortical impact injury (CCI). Shams received only anesthesia. Behavioral tests were administered at 1, 3, 5, 7, and 90 days post-injury (dpi). CCI animals showed significant motor and sensory deficits in the early (1–7 dpi) and long-term (90 dpi) stages of testing. Interestingly, sensory and subtle motor deficits in rmCHI animals were found at 90 dpi. Most importantly, depression-like behaviors and social passiveness were observed in rmCHI animals at 90 dpi. These data suggest that mild concussive injuries lead to motor and sensory deficits and affective disorders that are not observed after moderate TBI. PMID:26796696

  19. 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.

  20. Modulation of Synaptic Vesicle Exocytosis in Muscle-Dependent Long-Term Depression at the Amphibian Neuromuscular Junction

    PubMed Central

    Etherington, Sarah J.; Johnstone, Victoria P. A.; Everett, Alan W.

    2014-01-01

    We have labeled recycling synaptic vesicles at the somatic Bufo marinus neuromuscular junction with the styryl dye FM2-10 and provide direct evidence for refractoriness of exocytosis associated with a muscle activity-dependent form of long-term depression (LTD) at this synapse. FM2-10 dye unloading experiments demonstrated that the rate of vesicle exocytosis from the release ready pool (RRP) of vesicles was more than halved in the LTD (induced by 20 min of low frequency stimulation). Recovery from LTD, observed as a partial recovery of nerve-evoked muscle twitch amplitude, was accompanied by partial recovery of the refractoriness of RRP exocytosis. Unexpectedly, paired pulse plasticity, another routinely used indicator of presynaptic forms of synaptic plasticity, was unchanged in the LTD. We conclude that the LTD induces refractoriness of the neuromuscular vesicle release machinery downstream of presynaptic calcium entry. PMID:24489862

  1. Layer-specific endocannabinoid-mediated long-term depression of GABAergic neurotransmission onto principal neurons in mouse visual cortex.

    PubMed

    Sun, Wenjuan; Wang, Laijian; Li, Shuo; Tie, Xiaoxiu; Jiang, Bin

    2015-08-01

    Visually induced endocannabinoid-mediated long-term depression of GABAergic neurotransmission (iLTD) mediates the maturation of GABAergic release in layer 2/3 of visual cortex. Here we examined whether the maturation of GABAergic transmission in other layers of visual cortex also requires endocannabinoids. The developmental plasticity of GABAergic neurotransmission onto the principal neurons in different layers of mouse visual cortex was examined in cortical slices by whole-cell recordings of inhibitory postsynaptic currents evoked by presynaptic inhibitory inputs. Theta burst stimulation of GABAergic inputs induced an endocannabinoid-mediated long-term depression of GABAergic neurotransmission onto pyramidal cells in layer 2/3 from postnatal day (P)10 to 30 and in layer 5 from P10 to 40, whereas that of GABAergic inputs did not induce iLTD onto star pyramidal neurons in layer 4 at any time postnatally, indicating that this plasticity is laminar-specific. The developmental loss of iLTD paralleled the maturation of GABAergic inhibition in both layer 2/3 and layer 5. Visual deprivation delayed the developmental loss of iLTD in layers 3 and 5 during a critical period, while 2 days of light exposure eliminated iLTD in both layers. Furthermore, the GABAergic synapses in layers 2/3 and 5 did not normally mature in the type 1 cannabinoid receptor knock-out mice, whereas those in layer 4 did not require endocannabinoid receptor for maturation. These results suggest that visually induced endocannabinoid-dependent iLTD mediates the maturation of GABAergic release in extragranular layer rather than in granular layer of mouse visual cortex.

  2. Glutamatergic synapses are structurally and biochemically complex because of multiple plasticity processes: long-term potentiation, long-term depression, short-term potentiation and scaling.

    PubMed

    Lisman, John

    2017-03-05

    Synapses are complex because they perform multiple functions, including at least six mechanistically different forms of plasticity. Here, I comment on recent developments regarding these processes. (i) Short-term potentiation (STP), a Hebbian process that requires small amounts of synaptic input, appears to make strong contributions to some forms of working memory. (ii) The rules for long-term potentiation (LTP) induction in CA3 have been clarified: induction does not depend obligatorily on backpropagating sodium spikes but, rather, on dendritic branch-specific N-methyl-d-aspartate (NMDA) spikes. (iii) Late LTP, a process that requires a dopamine signal (and is therefore neoHebbian), is mediated by trans-synaptic growth of the synapse, a growth that occurs about an hour after LTP induction. (iv) LTD processes are complex and include both homosynaptic and heterosynaptic forms. (v) Synaptic scaling produced by changes in activity levels are not primarily cell-autonomous, but rather depend on network activity. (vi) The evidence for distance-dependent scaling along the primary dendrite is firm, and a plausible structural-based mechanism is suggested.Ideas about the mechanisms of synaptic function need to take into consideration newly emerging data about synaptic structure. Recent super-resolution studies indicate that glutamatergic synapses are modular (module size 70-80 nm), as predicted by theoretical work. Modules are trans-synaptic structures and have high concentrations of postsynaptic density-95 (PSD-95) and α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor. These modules function as quasi-independent loci of AMPA-mediated transmission and may be independently modifiable, suggesting a new understanding of quantal transmission.This article is part of the themed issue 'Integrating Hebbian and homeostatic plasticity.'

  3. 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.

  4. 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

  5. Immobilized contrast-enhanced MRI: Gadolinium-based long-term MR contrast enhancement of the vein graft vessel wall.

    PubMed

    Mitsouras, Dimitris; Vemula, Praveen Kumar; Yu, Peng; Tao, Ming; Nguyen, Binh T; Campagna, Christina M; Karp, Jeffrey M; Mulkern, Robert V; Ozaki, C Keith; Rybicki, Frank J

    2011-01-01

    An implantable MR contrast agent that can be covalently immobilized on tissue during surgery has been developed. The rationale is that a durable increase in tissue contrast using an implantable contrast agent can enhance postsurgical tissue differentiation using MRI. For small-vessel (e.g., vein graft) MRI, the direct benefit of such permanent "labeling" of the vessel wall by modification of its relaxation properties is to achieve more efficient imaging. This efficiency can be realized as either increased contrast leading to more accurate delineation of vessel wall and lesion tissue boundaries, or, faster imaging without penalizing contrast-to-noise ratio, or a combination thereof. We demonstrate, for the first time, stable long-term MRI enhancement using such an exogenous contrast mechanism based on immobilizing a modified diethylenetriaminepentaacetic acid gadolinium(3+) dihydrogen complex on a human vein using a covalent amide bond. Signal enhancement due to the covalently immobilized contrast agent is demonstrated for excised human vein specimens imaged at 3 T, and its long-term stability is demonstrated during a 4-month incubation period.

  6. Dopamine-dependent long-term depression is expressed in striatal spiny neurons of both direct and indirect pathways: implications for Parkinson's disease.

    PubMed

    Bagetta, Vincenza; Picconi, Barbara; Marinucci, Silvia; Sgobio, Carmelo; Pendolino, Valentina; Ghiglieri, Veronica; Fusco, Francesca R; Giampà, Carmen; Calabresi, Paolo

    2011-08-31

    Striatal medium spiny neurons (MSNs) are divided into two subpopulations exerting distinct effects on motor behavior. Transgenic mice carrying bacterial artificial chromosome (BAC) able to confer cell type-specific expression of enhanced green fluorescent protein (eGFP) for dopamine (DA) receptors have been developed to characterize differences between these subpopulations. Analysis of these mice, in contrast with original pioneering studies, showed that striatal long-term depression (LTD) was expressed in indirect but not in the direct pathway MSNs. To address this mismatch, we applied a new approach using combined BAC technology and receptor immunohistochemistry. We demonstrate that, in physiological conditions, DA-dependent LTD is expressed in both pathways showing that the lack of synaptic plasticity found in D(1) eGFP mice is associated to behavioral deficits. Our findings suggest caution in the use of this tool and indicate that the "striatal segregation" hypothesis might not explain all synaptic dysfunctions in Parkinson's disease.

  7. The Sodium Channel β4 Auxiliary Subunit Selectively Controls Long-Term Depression in Core Nucleus Accumbens Medium Spiny Neurons

    PubMed Central

    Ji, Xincai; Saha, Sucharita; Gao, Guangping; Lasek, Amy W.; Homanics, Gregg E.; Guildford, Melissa; Tapper, Andrew R.; Martin, Gilles E.

    2017-01-01

    Voltage-gated sodium channels are essential for generating the initial rapid depolarization of neuronal membrane potential during action potentials (APs) that enable cell-to-cell communication, the propagation of signals throughout the brain, and the induction of synaptic plasticity. Although all brain neurons express one or several variants coding for the core pore-forming sodium channel α subunit, the expression of the β (β1–4) auxiliary subunits varies greatly. Of particular interest is the β4 subunit, encoded by the Scn4b gene, that is highly expressed in dorsal and ventral (i.e., nucleus accumbens – NAc) striata compared to other brain regions, and that endows sodium channels with unique gating properties. However, its role on neuronal activity, synaptic plasticity, and behaviors related to drugs of abuse remains poorly understood. Combining whole-cell patch-clamp recordings with two-photon calcium imaging in Scn4b knockout (KO) and knockdown mice, we found that Scn4b altered the properties of APs in core accumbens medium spiny neurons (MSNs). These alterations are associated with a reduction of the probability of MSNs to evoke spike-timing-dependent long-term depression (tLTD) and a reduced ability of backpropagating APs to evoke dendritic calcium transients. In contrast, long-term potentiation (tLTP) remained unaffected. Interestingly, we also showed that amphetamine-induced locomotor activity was significantly reduced in male Scn4b KO mice compared to wild-type controls. Taken together, these data indicate that the Scn4b subunit selectively controls tLTD by modulating dendritic calcium transients evoked by backpropagating APs. PMID:28243192

  8. Resting state synchrony in long-term abstinent alcoholics: Effects of a current major depressive disorder diagnosis.

    PubMed

    Fein, George; Camchong, Jazmin; Cardenas, Valerie A; Stenger, Andy

    2017-03-01

    Alcoholism is characterized by a lack of control over an impulsive and compulsive drive toward excessive alcohol consumption despite significant negative consequences; our previous work demonstrated that successful abstinence is characterized by decreased resting-state synchrony (RSS) as measured with functional magnetic resonance imaging (fMRI), within appetitive drive networks and increased RSS in emotion regulation and inhibitory executive control networks. Our hypothesis is that LTAA (Long-Term Abstinent Alcoholics) with a current major depressive disorder (MDD) drank primarily to deal with the negative affect associated with their MDD and not because of a heightened externalizing diathesis (including heightened appetitive drive), and consequently, in achieving and maintaining abstinence, such individuals would not exhibit the RSS adaptations characteristic of pure alcoholics. We studied 69 NSAC (Non Substance Abusing Controls) and 40 LTAA (8 with current MDD, 32 without a current MDD) using resting-state fMRI and seed based connectivity analyses. In the inhibitory executive control network (nucleus accumbens vs. left dorsolateral prefrontal cortex), LTAA with a current MDD showed increased synchrony compared to NSAC. In the emotion regulation executive control network (subgenual anterior cingulate cortex vs. right dorsolateral prefrontal cortex), LTAA with current MDD did not show increased RSS. In the appetitive drive networks (nucleus accumbens vs, aspects of the caudate nucleus and thalamus), LTAA with a current MDD did not show a reduction of RSS compared to NSAC, but LTAA without a current MDD did. These results suggest different pathways to their alcohol dependence in LTAA with vs. without a current MDD, and different patterns of brain activity in long-term abstinence, suggesting different treatment needs.

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

    PubMed

    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.

  10. 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

  11. The effectiveness of group reminiscence therapy for loneliness, anxiety and depression in older adults in long-term care: a systematic review.

    PubMed

    Syed Elias, Sharifah Munirah; Neville, Christine; Scott, Theresa

    2015-01-01

    Loneliness, anxiety and depression are common problems for older adults in long-term care. Reminiscence therapy is a non-pharmacological intervention that may be of some benefit. In comparison to individual reminiscence therapy, group reminiscence therapy is a preferred option when dealing with the resource constraints of long-term care. The aim of this paper was to systematically review the literature in order to explore the effectiveness of group reminiscence therapy for older adults with loneliness, anxiety and depression in long-term care. Results indicated that group reminiscence therapy is an effective treatment for depression in older adults, however to date, there is limited research support for its effectiveness to treat loneliness and anxiety. Further research and an improvement in methodological quality, such as using qualitative and mixed methods approaches, is recommended to help establish an evidence base and provide better understanding of the effectiveness of group reminiscence therapy.

  12. mGlu5 receptors and cellular prion protein mediate amyloid-β-facilitated synaptic long-term depression in vivo

    PubMed Central

    Hu, Neng-Wei; Nicoll, Andrew J.; Zhang, Dainan; Mably, Alexandra J.; O’Malley, Tiernan; Purro, Silvia A.; Terry, Cassandra; Collinge, John; Walsh, Dominic M.; Rowan, Michael J.

    2014-01-01

    NMDA-type glutamate receptors (NMDARs) are currently regarded as paramount in the potent and selective disruption of synaptic plasticity by Alzheimer’s disease amyloid β-protein (Aβ). Non-NMDAR mechanisms remain relatively unexplored. Here we describe how Aβ facilitates NMDAR-independent long-term depression of synaptic transmission in the hippocampus in vivo. Synthetic Aβ and Aβ in soluble extracts of Alzheimer’s disease brain usurp endogenous acetylcholine muscarinic receptor-dependent long-term depression, to enable long-term depression that required metabotropic glutamate-5 receptors (mGlu5Rs). We also find that mGlu5Rs are essential for Aβ-mediated inhibition of NMDAR-dependent long-term potentiation in vivo. Blocking Aβ binding to cellular prion protein with antibodies prevents the facilitation of long-term depression. Our findings uncover an overarching role for Aβ-PrPC-mGlu5R interplay in mediating both LTD facilitation and LTP inhibition, encompassing NMDAR-mediated processes that were previously considered primary. PMID:24594908

  13. Control Design Strategies to Enhance Long-Term Aircraft Structural Integrity

    NASA Technical Reports Server (NTRS)

    Newman, Brett A.

    1999-01-01

    Over the operational lifetime of both military and civil aircraft, structural components are exposed to hundreds of thousands of low-stress repetitive load cycles and less frequent but higher-stress transient loads originating from maneuvering flight and atmospheric gusts. Micro-material imperfections in the structure, such as cracks and debonded laminates, expand and grow in this environment, reducing the structural integrity and shortening the life of the airframe. Extreme costs associated with refurbishment of critical load-bearing structural components in a large fleet, or altogether reinventoring the fleet with newer models, indicate alternative solutions for life extension of the airframe structure are highly desirable. Increased levels of operational safety and reliability are also important factors influencing the desirability of such solutions. One area having significant potential for impacting crack growth/fatigue damage reduction and structural life extension is flight control. To modify the airframe response dynamics arising from command inputs and gust disturbances, feedback loops are routinely applied to vehicles. A dexterous flight control system architecture senses key vehicle motions and generates critical forces/moments at multiple points distributed throughout the airframe to elicit the desired motion characteristics. In principle, these same control loops can be utilized to influence the level of exposure to harmful loads during flight on structural components. Project objectives are to investigate and/or assess the leverage control has on reducing fatigue damage and enhancing long-term structural integrity, without degrading attitude control and trajectory guidance performance levels. In particular, efforts have focused on the effects inner loop control parameters and architectures have on fatigue damage rate. To complete this research, an actively controlled flexible aircraft model and a new state space modeling procedure for crack growth

  14. 76 FR 71560 - Notice of a Public Meeting on Long Term 2 Enhanced Surface Water Treatment Rule: Initiate...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-11-18

    ... AGENCY Notice of a Public Meeting on Long Term 2 Enhanced Surface Water Treatment Rule: Initiate Regulatory Review--Cryptosporidium Analytical Method Improvements and Update on Source Water Monitoring... Water Treatment Rule (LT2 rule). This is the first of at least two meetings on the LT2 rule that...

  15. Long-Term Effectiveness of the SpeechEasy Fluency-Enhancement Device

    ERIC Educational Resources Information Center

    Gallop, Ronald F.; Runyan, Charles M.

    2012-01-01

    The SpeechEasy has been found to be an effective device for reduction of stuttering frequency for many people who stutter (PWS); published studies typically have compared stuttering reduction at initial fitting of the device to results achieved up to one year later. This study examines long-term effectiveness by examining whether effects of the…

  16. Stress administered prior to encoding impairs neutral but enhances emotional long-term episodic memories.

    PubMed

    Payne, Jessica D; Jackson, Eric D; Hoscheidt, Siobhan; Ryan, Lee; Jacobs, W Jake; Nadel, Lynn

    2007-12-01

    Stressful events frequently comprise both neutral and emotionally arousing information, yet the impact of stress on emotional and neutral events is still not fully understood. The hippocampus and frontal cortex have dense concentrations of receptors for stress hormones, such as cortisol, which at high levels can impair performance on hippocampally dependent memory tasks. Yet, the same stress hormones can facilitate memory for emotional information, which involves interactions between the hippocampus and amygdala. Here, we induced psychosocial stress prior to encoding and examined its long-term effects on memory for emotional and neutral episodes. The stress manipulation disrupted long-term memory for a neutral episode, but facilitated long-term memory for an equivalent emotional episode compared with a control condition. The stress manipulation also increased salivary cortisol, catecholamines as indicated by the presence of alpha-amylase, heart rate, and subjectively reported stress. Stressed subjects reported more false memories than nonstressed control subjects, and these false memories correlated positively with cortisol levels, providing evidence for a relationship between stress and false memory formation. Our results demonstrate that stress, when administered prior to encoding, produces different patterns of long-term remembering for neutral and emotional episodes. These differences likely emerge from differential actions of stress hormones on memory-relevant regions of the brain.

  17. Enhanced photovoltaic properties and long-term stability in plasmonic dye-sensitized solar cells via noncorrosive redox mediator.

    PubMed

    Jung, Heesuk; Koo, Bonkee; Kim, Jae-Yup; Kim, Taehee; Son, Hae Jung; Kim, BongSoo; Kim, Jin Young; Lee, Doh-Kwon; Kim, Honggon; Cho, Jinhan; Ko, Min Jae

    2014-11-12

    We demonstrate the localized surface plasmon resonance (LSPR) effect, which can enhance the photovoltaic properties of dye-sensitized solar cells (DSSCs), and the long-term stability of size-controlled plasmonic structures using a noncorrosive redox mediator. Gold nanoparticles (Au NPs) were synthesized with a phase transfer method based on ligand exchange. This synthetic method is advantageous because the uniformly sized Au NPs, can be mass produced and easily applied to DSSC photoanodes. The plasmonic DSSCs showed an 11% improvement of power conversion efficiency due to the incorporation of 0.07 wt % Au NPs, compared to the reference DSSCs without Au NPs. The improved efficiency was primarily due to the enhanced photocurrent generation by LSPR effect. With the cobalt redox mediator, the long-term stability of the plasmonic structures also significantly increased. The plasmonic DSSCs with cobalt(II/III) tris(2,2'-bipyridine) ([Co(bpy)3](2+/3+)) redox mediator maintained the LSPR effect with stable photovoltaic performance for 1000 h. This is, to our knowledge, the first demonstration of the long-term stability of plasmonic nanostructures in plasmonic DSSCs based on liquid electrolytes. As a result, the enhanced long-term stability of plasmonic NPs via a noncorrosive redox mediator will increase the feasibility of plasmonic DSSCs.

  18. A Model of Induction of Cerebellar Long-Term Depression Including RKIP Inactivation of Raf and MEK

    PubMed Central

    Hepburn, Iain; Jain, Anant; Gangal, Himanshu; Yamamoto, Yukio; Tanaka-Yamamoto, Keiko; De Schutter, Erik

    2017-01-01

    We report an updated stochastic model of cerebellar Long Term Depression (LTD) with improved realism. Firstly, we verify experimentally that dissociation of Raf kinase inhibitor protein (RKIP) from Mitogen-activated protein kinase kinase (MEK) is required for cerebellar LTD and add this interaction to an earlier published model, along with the known requirement of dissociation of RKIP from Raf kinase. We update Ca2+ dynamics as a constant-rate influx, which captures experimental input profiles accurately. We improve α-amino-3-hydroxy-5-methyl-4 isoxazolepropionic acid (AMPA) receptor interactions by adding phosphorylation and dephosphorylation of AMPA receptors when bound to glutamate receptor interacting protein (GRIP). The updated model is tuned to reproduce experimental Ca2+ peak vs. LTD amplitude curves at four different Ca2+ pulse durations as closely as possible. We find that the updated model is generally more robust with these changes, yet we still observe some sensitivity of LTD induction to copy number of the key signaling molecule Protein kinase C (PKC). We predict natural variability in this number by stochastic diffusion may influence the probabilistic LTD response to Ca2+ input in Purkinje cell spines and propose this as an extra source of stochasticity that may be important also in other signaling systems. PMID:28220061

  19. Impaired cognition, sensorimotor gating, and hippocampal long-term depression in mice lacking the prostaglandin E2 EP2 receptor

    PubMed Central

    Savonenko, A.; Munoz, P.; Melnikova, T.; Wang, Q.; Liang, X.; Breyer, R. M.; Montine, T. J.; Kirkwood, A.; Andreasson, K.

    2009-01-01

    Cyclooxygenase-2 (COX-2) is a neuronal immediate early gene that is regulated by N-methyl D aspartate (NMDA) receptor activity. COX-2 enzymatic activity catalyzes the first committed step in prostaglandin synthesis. Recent studies demonstrate an emerging role for the downstream PGE2 EP2 receptor in diverse models of activity-dependent synaptic plasticity and a significant function in models of neurological disease including cerebral ischemia, Familial Alzheimer’s disease, and Familial amyotrophic lateral sclerosis. Little is known, however, about the normal function of the EP2 receptor in behavior and cognition. Here we report that deletion of the EP2 receptor leads to significant cognitive deficits in standard tests of fear and social memory. EP2 −/− mice also demonstrated impaired prepulse inhibition (PPI) and heightened anxiety, but normal startle reactivity, exploratory behavior, and spatial reference memory. This complex behavioral phenotype of EP2−/− mice was associated with a deficit in long-term depression (LTD) in hippocampus. Our findings suggest that PGE2 signaling via the EP2 receptors plays an important role in cognitive and emotional behaviors that recapitulate some aspects of human psychopathology related to schizophrenia. PMID:19416671

  20. Locus Coeruleus Stimulation Facilitates Long-Term Depression in the Dentate Gyrus That Requires Activation of β-Adrenergic Receptors

    PubMed Central

    Hansen, Niels; Manahan-Vaughan, Denise

    2015-01-01

    Synaptic plasticity comprises a cellular mechanism through which the hippocampus most likely enables memory formation. Neuromodulation, related to arousal, is a key aspect in information storage. The activation of locus coeruleus (LC) neurons by novel experience leads to noradrenaline release in the hippocampus at the level of the dentate gyrus (DG). We explored whether synaptic plasticity in the DG is influenced by activation of the LC via electrical stimulation. Coupling of test-pulses that evoked stable basal synaptic transmission in the DG with stimulation of the LC induced β-adrenoreceptor-dependent long-term depression (LTD) at perforant path–DG synapses in adult rats. Furthermore, persistent LTD (>24 h) induced by perforant path stimulation also required activation of β-adrenergic receptors: Whereas a β-adrenergic receptor antagonist (propranolol) prevented, an agonist (isoproterenol) strengthened the persistence of LTD for over 24 h. These findings support the hypothesis that persistent LTD in the DG is modulated by β-adrenergic receptors. Furthermore, LC activation potently facilitates DG LTD. This suggests in turn that synaptic plasticity in the DG is tightly regulated by activity in the noradrenergic system. This may reflect the role of the LC in selecting salient information for subsequent synaptic processing in the hippocampus. PMID:24464942

  1. Synaptic P-Rex1 signaling regulates hippocampal long-term depression and autism-like social behavior

    PubMed Central

    Li, Jun; Chai, Anping; Wang, Lifang; Ma, Yuanlin; Wu, Zhiliu; Yu, Hao; Mei, Liwei; Lu, Lin; Zhang, Chen; Yue, Weihua; Xu, Lin; Rao, Yi; Zhang, Dai

    2015-01-01

    Autism spectrum disorders (ASDs) are a group of highly inheritable mental disorders associated with synaptic dysfunction, but the underlying cellular and molecular mechanisms remain to be clarified. Here we report that autism in Chinese Han population is associated with genetic variations and copy number deletion of P-Rex1 (phosphatidylinositol-3,4,5-trisphosphate-dependent Rac exchange factor 1). Genetic deletion or knockdown of P-Rex1 in the CA1 region of the hippocampus in mice resulted in autism-like social behavior that was specifically linked to the defect of long-term depression (LTD) in the CA1 region through alteration of AMPA receptor endocytosis mediated by the postsynaptic PP1α (protein phosphase 1α)–P-Rex1–Rac1 (Ras-related C3 botulinum toxin substrate 1) signaling pathway. Rescue of the LTD in the CA1 region markedly alleviated autism-like social behavior. Together, our findings suggest a vital role of P-Rex1 signaling in CA1 LTD that is critical for social behavior and cognitive function and offer new insight into the etiology of ASDs. PMID:26621702

  2. FAAH inhibition produces antidepressant-like efforts of mice to acute stress via synaptic long-term depression.

    PubMed

    Wang, Ying; Zhang, Xia

    2017-05-01

    Recent studies have shown that inhibition of fatty acid amide hydrolase (FAAH), the major degradative enzyme of the endocannabinoid N-arachidonoylethanolamine (AEA), produced antidepressant behavioral responses, but its underlying mechanism is not clear. Here we find that a systemic administration of the FAAH inhibitor PF3845 or an intra-CA1 application of AEA elicits an in vivo long-term depression (LTD) at excitatory glutamatergic CA3-CA1 synapses of the hippocampus. The PF3845- and/or AEA-elicited LTD are abolished by the LTD-blocking peptide Tat-GluR2. PF3845 significantly decreases passive behavioral coping of naïve mice to acute inescapable stress, which is also abolished by Tat-GluR2 peptide. However, PF3845 does not significantly affect sucrose assumption ratio of mice receiving chronic administration of corticosterone. These results suggest that FAAH inhibitors are able to produce antidepressant effects in naïve animals in response to acute stress through LTD at hippocampal glutamatergic CA3-CA1 synapses.

  3. Antimicrobial films containing microparticles for the enhancement of long-term sustained release.

    PubMed

    Bile, Jessica; Bolzinger, Marie-Alexandrine; Valour, Jean-Pierre; Fessi, Hatem; Chevalier, Yves

    2016-01-01

    Coated packagings with thin films containing antimicrobial agents are an alternative technology to ensure the protection of products against microbial contaminations. Indeed, they allow lowering the antimicrobial concentration in the bulk of the product while meeting the safety requirements and the growing consumer demand for low preservative concentrations. Microencapsulation is a suitable way for controlling active agent release and providing a long-term activity. This work aims at combining both technical solutions with coatings containing antimicrobial microparticles for the achievement of long-term sustained release. Polyethylene surfaces were functionalized with microparticles of poly(methyl methacrylate) (PMMA) loaded with phenylethyl alcohol (PEA) as antimicrobial agent by the dip coating process using a polyurethane binder. The release of PEA into water from coated polyethylene surfaces and from PMMA microparticles was investigated to assess the sustained release and its mechanisms. Films with various thicknesses of 400-1000 µm containing antimicrobial microparticles demonstrated unusual long-term release longer than 3 months. The diffusion of the antimicrobial agent through PMMA was the rate limiting step of the sustained release. PEA release increased as the contact area of the protruding microparticles with the external medium increased and the thickness of the film decreased. Such antimicrobial agents encapsulated inside thin coatings are promising with regards to antimicrobial preservation of products along their full shelf-life.

  4. Pragmatic randomized controlled trial of long-term psychoanalytic psychotherapy for treatment-resistant depression: the Tavistock Adult Depression Study (TADS)

    PubMed Central

    Fonagy, Peter; Rost, Felicitas; Carlyle, Jo-anne; McPherson, Susan; Thomas, Rachel; Pasco Fearon, RM; Goldberg, David; Taylor, David

    2015-01-01

    This pragmatic randomized controlled trial tested the effectiveness of long-term psychoanalytic psychotherapy (LTPP) as an adjunct to treatment-as-usual according to UK national guidelines (TAU), compared to TAU alone, in patients with long-standing major depression who had failed at least two different treatments and were considered to have treatment-resistant depression. Patients (N=129) were recruited from primary care and randomly allocated to the two treatment conditions. They were assessed at 6-monthly intervals during the 18 months of treatment and at 24, 30 and 42 months during follow-up. The primary outcome measure was the 17-item version of the Hamilton Depression Rating Scale (HDRS-17), with complete remission defined as a HDRS-17 score ≤8, and partial remission defined as a HDRS-17 score ≤12. Secondary outcome measures included self-reported depression as assessed by the Beck Depression Inventory - II, social functioning as evaluated by the Global Assessment of Functioning, subjective wellbeing as rated by the Clinical Outcomes in Routine Evaluation - Outcome Measure, and satisfaction with general activities as assessed by the Quality of Life Enjoyment and Satisfaction Questionnaire. Complete remission was infrequent in both groups at the end of treatment (9.4% in the LTPP group vs. 6.5% in the control group) as well as at 42-month follow-up (14.9% vs. 4.4%). Partial remission was not significantly more likely in the LTPP than in the control group at the end of treatment (32.1% vs. 23.9%, p=0.37), but significant differences emerged during follow-up (24 months: 38.8% vs. 19.2%, p=0.03; 30 months: 34.7% vs. 12.2%, p=0.008; 42 months: 30.0% vs. 4.4%, p=0.001). Both observer-based and self-reported depression scores showed steeper declines in the LTPP group, alongside greater improvements on measures of social adjustment. These data suggest that LTPP can be useful in improving the long-term outcome of treatment-resistant depression. End

  5. The GABA[subscript A] Receptor Agonist Muscimol Induces an Age- and Region-Dependent Form of Long-Term Depression in the Mouse Striatum

    ERIC Educational Resources Information Center

    Zhang, Xiaoqun; Yao, Ning; Chergui, Karima

    2016-01-01

    Several forms of long-term depression (LTD) of glutamatergic synaptic transmission have been identified in the dorsal striatum and in the nucleus accumbens (NAc). Such experience-dependent synaptic plasticity might play important roles in reward-related learning. The GABA[subscript A] receptor agonist muscimol was recently found to trigger a…

  6. Long-Term Outcomes of an Australian Universal Prevention Trial of Anxiety and Depression Symptoms in Children and Youth: An Evaluation of the Friends Program

    ERIC Educational Resources Information Center

    Barrett, Paula M.; Farrell, Lara J.; Ollendick, Thomas H.; Dadds, Mark

    2006-01-01

    This study evaluated the long-term effectiveness of the FRIENDS Program in reducing anxiety and depression in a sample of children from Grade 6 and Grade 9 in comparison to a control condition. Longitudinal data for Lock and Barrett's (2003) universal prevention trial is presented, along with data from 12-month follow-up to 24- and 36-month…

  7. For Individuals with Obstructive Sleep Apnea, Institution of CPAP therapy is Associated with an Amelioration of Symptoms of Depression which is Sustained Long Term

    PubMed Central

    Schwartz, Daniel J.; Karatinos, Gillian

    2007-01-01

    Objective: To assess the sustainability of an improvement in symptoms of depression using CPAP therapy in patients with obstructive sleep apnea. Patients/Methods: Patients referred to our center for evaluation of obstructive sleep apnea who had a respiratory disturbance index (RDI) of ≥15 and who demonstrated a significant response to CPAP (50% or greater drop in RDI), were evaluated for symptoms of depression using the Beck Depression Inventory-Fast Screen for Medical Patients (BDI). These individuals were asked to complete the BDI assessment again after 4 to 6 weeks of treatment with CPAP (short-term follow-up), and then reassessed approximately one year later (long-term follow-up). Results: In this group of patients, the institution of CPAP therapy resulted in a significant decrease in those symptoms of depression assessed by the BDI at both the short-term and long-term follow-up periods. Conclusions: For patients with OSA who continue CPAP therapy, we noted a statistically significant, sustained improvement in those symptoms of depression measured by the BDI. Citation: Schwartz DJ; Karatinos G. For individuals with obstructive sleep apnea, institution of cpap therapy is associated with an amelioration of symptoms of depression which is sustained long term. J Clin Sleep Med 2007;3(6):631-635. PMID:17993046

  8. Overexpression of Protein Kinase Mζ in the Prelimbic Cortex Enhances the Formation of Long-Term Fear Memory

    PubMed Central

    Xue, Yan-Xue; Zhu, Zhen-Zhen; Han, Hai-Bin; Liu, Jian-Feng; Meng, Shi-Qiu; Chen, Chen; Yang, Jian-Li; Wu, Ping; Lu, Lin

    2015-01-01

    Neuroplasticity in the prefrontal cortex (PFC) after fear conditioning has been suggested to regulate the formation and expression of fear memory. Protein kinase Mζ (PKMζ), an isoform of protein kinase C with persistent activity, is involved in the formation and maintenance of memory. However, less is known about the role of PKMζ in the PFC in the formation of fear memory. We investigated whether the overexpression of PKMζ enhances the formation of auditory fear memory in rats. We found that microinfusion of lentiviral vector-expressing PKMζ into the prelimbic cortex (PrL) selectively enhanced the expression of PKMζ without influencing the expression of other isoforms of PKC. The overexpression of PKMζ in the PrL enhanced the formation of long-term fear memory without affecting short-term fear memory, whereas the overexpression of PKMζ in the infralimbic cortex had no effect on either short-term or long-term fear memory. The overexpression of PKMζ in the PrL had no effect on anxiety-like behavior or locomotor activity. We also found that PKMζ overexpression potentiated the fear conditioning-induced increase in the membrane levels of glutamate subunit 2 of AMPA receptors in the PrL. These results demonstrate that the overexpression of PKMζ in the PrL but not infralimbic cortex selectively enhanced the formation of long-term fear memory, and PKMζ in the PrL may be involved in the formation of fear memory. PMID:25722116

  9. Infarction of Uterine Fibroids After Embolization: Relationship Between Postprocedural Enhanced MRI Findings and Long-Term Clinical Outcomes

    SciTech Connect

    Katsumori, Tetsuya Kasahara, Toshiyuki; Kin, Yoko; Nozaki, Taiki

    2008-01-15

    Purpose. To retrospectively evaluate the relationship between the degree of infarction of uterine fibroids on enhanced MRI after embolization and long-term clinical outcomes. Methods. During 92 months, 290 consecutive patients with symptomatic uterine fibroids were treated with embolization; 221 who underwent enhanced MRI before embolization and 1 week after embolization were included in this study. The infarction rates of all fibroid tissue were assessed using enhanced MRI after embolization. Patients were divided into three groups according to the infarction rates: group A (100% infarction, n 142), group B (90-99% infarction, n = 74), group C (<90% infarction, n = 5). The cumulative rates of clinical outcomes were compared among groups using the Kaplan-Meier limited method. Results. Group A had a significantly higher rate of symptom control than groups B and C. The cumulative rates of symptom control at 5 years were 93%, 71%, and 60% in groups A, B, and C, respectively. Group A had a significantly lower rate of gynecologic intervention after embolization than groups B and C. The cumulative rates of additional gynecologic intervention at 5 years were 3%, 15%, and 20% in groups A, B, and C, respectively. Conclusions. The degree of infarction of uterine fibroids after embolization on enhanced MRI was related to long-term clinical outcomes. Complete infarction of all fibroid tissue can induce a higher rate of symptom control, with a lower rate of additional gynecologic intervention in the long term compared with incomplete infarction of fibroid tissue.

  10. Endocannabinoid-mediated long-term depression of afferent excitatory synapses in hippocampal pyramidal cells and GABAergic interneurons.

    PubMed

    Péterfi, Zoltán; Urbán, Gabriella M; Papp, Orsolya I; Németh, Beáta; Monyer, Hannah; Szabó, Gábor; Erdélyi, Ferenc; Mackie, Ken; Freund, Tamás F; Hájos, Norbert; Katona, István

    2012-10-10

    Although endocannabinoids have emerged as essential retrograde messengers in several forms of synaptic plasticity, it remains controversial whether they mediate long-term depression (LTD) of glutamatergic synapses onto excitatory and inhibitory neurons in the hippocampus. Here, we show that parvalbumin- and somatostatin/metabotropic glutamate receptor 1(a) (mGlu(1a))-positive GABAergic interneurons express diacylglycerol lipase-α (DGL-α), a synthesizing enzyme of the endocannabinoid 2-arachidonoylglycerol (2-AG), albeit at lower levels than principal cells. Moreover, this lipase accumulates postsynaptically around afferent excitatory synapses in all three cell types. To address the role of retrograde 2-AG signaling in LTD, we investigated two forms: (1) produced by postsynaptic spiking paired with subsequent presynaptic stimulation or (2) induced by group I mGlu activation by (S)-3,5-dihydroxyphenylglycine (DHPG). Neither form of LTD was evoked in the presence of the mGlu(5) antagonist MPEP [2-methyl-6-(phenylethynyl)-pyridine], the DGL inhibitor THL [N-formyl-l-leucine (1S)-1-[[(2S,3S)-3-hexyl-4-oxo-2-oxetanyl]methyl]dodecyl ester], or the intracellularly applied Ca(2+) chelator BAPTA in CA1 pyramidal cells, fast-spiking interneurons (representing parvalbumin-containing cells) and interneurons projecting to stratum lacunosum-moleculare (representing somatostatin/mGlu(1a)-expressing interneurons). Both forms of LTD were completely absent in CB(1) cannabinoid receptor knock-out mice, whereas pharmacological blockade of CB(1) led to inconsistent results. Notably, in accordance with their lower DGL-α level, a higher stimulation frequency or higher DHPG concentration was required for LTD induction in interneurons compared with pyramidal cells. These findings demonstrate that hippocampal principal cells and interneurons produce endocannabinoids to mediate LTD in a qualitatively similar, but quantitatively different manner. The shifted induction threshold implies that

  11. Heterosynaptic long-term depression of craniofacial nociception: divergent effects on pain perception and blink reflex in man.

    PubMed

    Yekta, Sareh Said; Lamp, Susanne; Ellrich, Jens

    2006-04-01

    Noxious low-frequency stimulation (LFS) of presynaptic nerve fibers induces long-term depression (LTD) of synaptic transmission. In vitro studies suggest a sole homosynaptic effect. Consequently, the present study addressed the hypothesis that LTD of craniofacial nociception in man is mediated by a homosynaptic mechanism. Nociceptive supraorbital afferents were excited by electric pulses via a concentric electrode in ten healthy volunteers. The electrically evoked bilateral blink reflex (BR) was recorded from both orbicularis oculi muscles by surface electrodes. The BR was evoked in blocks of ten electric stimuli each (0.1 Hz) with an interblock interval of 8 min. Conditioning noxious LFS (1 Hz, 20 min) was applied via concentric electrode either to the same site as BR test stimuli (ipsilateral) or to the corresponding contralateral forehead area (contralateral). LFS and test stimulus intensities corresponded to about threefold the pain threshold. After three baseline stimulus blocks, either conditioning ipsilateral or contralateral LFS were applied or stimulation was interrupted for 20 min as a control task. Afterwards, test stimulation blocks were continued for 40 min. Each volunteer participated in all three sessions on different days. Noxious LFS induced LTD of the BR independently from the side of conditioning stimulation. Pain perception decreased after ipsilateral LFS but not after contralateral LFS. The bilateral effect of noxious LFS on the BR provides evidence for heterosynaptic LTD based on bilateral projections of supraorbital nerve afferents onto spinal trigeminal nuclei. The divergent effect on pain perception may be due to a preferential contralateral projection of nociceptive afferents onto reflex interneurons but not onto trigeminothalamic projection neurons.

  12. Endocannabinoids Mediate Muscarinic Acetylcholine Receptor-Dependent Long-Term Depression in the Adult Medial Prefrontal Cortex

    PubMed Central

    Martin, Henry G. S.; Bernabeu, Axel; Lassalle, Olivier; Bouille, Clément; Beurrier, Corinne; Pelissier-Alicot, Anne-Laure; Manzoni, Olivier J.

    2015-01-01

    Cholinergic inputs into the prefrontal cortex (PFC) are associated with attention and cognition; however there is evidence that acetylcholine also has a role in PFC dependent learning and memory. Muscarinic acetylcholine receptors (mAChR) in the PFC can induce synaptic plasticity, but the underlying mechanisms remain either opaque or unresolved. We have characterized a form of mAChR mediated long-term depression (LTD) at glutamatergic synapses of layer 5 principal neurons in the adult medial PFC. This mAChR LTD is induced with the mAChR agonist carbachol and inhibited by selective M1 mAChR antagonists. In contrast to other cortical regions, we find that this M1 mAChR mediated LTD is coupled to endogenous cannabinoid (eCB) signaling. Inhibition of the principal eCB CB1 receptor blocked carbachol induced LTD in both rats and mice. Furthermore, when challenged with a sub-threshold carbachol application, LTD was induced in slices pretreated with the monoacylglycerol lipase (MAGL) inhibitor JZL184, suggesting that the eCB 2-arachidonylglyerol (2-AG) mediates M1 mAChR LTD. Yet, when endogenous acetylcholine was released from local cholinergic afferents in the PFC using optogenetics, it failed to trigger eCB-LTD. However coupling patterned optical and electrical stimulation to generate local synaptic signaling allowed the reliable induction of LTD. The light—electrical pairing induced LTD was M1 mAChR and CB1 receptor mediated. This shows for the first time that connecting excitatory synaptic activity with coincident endogenously released acetylcholine controls synaptic gain via eCB signaling. Together these results shed new light on the mechanisms of synaptic plasticity in the adult PFC and expand on the actions of endogenous cholinergic signaling. PMID:26648844

  13. Reassessment of long-term depression in cerebellar Purkinje cells in mice carrying mutated GluA2 C terminus

    PubMed Central

    Yamaguchi, Kazuhiko; Itohara, Shigeyoshi; Ito, Masao

    2016-01-01

    Long-term depression (LTD) of synaptic transmission from parallel fibers (PFs) to a Purkinje cell (PC) in the cerebellum has been considered to be a core mechanism of motor learning. Recently, however, discrepancies between LTD and motor learning have been reported in mice with a mutation that targeted the expression of PF–PC LTD by blocking AMPA-subtype glutamate receptor internalization regulated via the phosphorylation of AMPA receptors. In these mice, motor learning behavior was normal, but no PF–PC LTD was observed. We reexamined slices obtained from these GluA2 K882A and GluA2 Δ7 knockin mutants at 3–6 mo of age. The conventional protocols of stimulation did not induce LTD in these mutant mice, as previously reported, but surprisingly, LTD was induced using certain modified protocols. Such modifications involved increases in the number of PF stimulation (from one to two or five), replacement of climbing fiber stimulation with somatic depolarization (50 ms), filling a patch pipette with a Cs+-based solution, or extension of the duration of conjunction. We also found that intracellular infusion of a selective PKCα inhibitor (Gö6976) blocked LTD induction in the mutants, as in WT, suggesting that functional compensation occurred downstream of PKCα. The possibility that LTD in the mutants was caused by changes in membrane resistance, access resistance, or presynaptic property was excluded. The present results demonstrate that LTD is inducible by intensified conjunctive stimulations even in K882A and Δ7 mutants, indicating no contradiction against the LTD hypothesis of motor learning. PMID:27551099

  14. Folic Acid Alters Methylation Profile of JAK-STAT and Long-Term Depression Signaling Pathways in Alzheimer's Disease Models.

    PubMed

    Li, Wen; Liu, Huan; Yu, Min; Zhang, Xumei; Zhang, Yan; Liu, Hongbo; Wilson, John X; Huang, Guowei

    2016-11-01

    Dementia has emerged as a major societal issue because of the worldwide aging population and the absence of any effective treatment. DNA methylation is an epigenetic mechanism that evidently plays a role in Alzheimer's disease (AD). Folate acts through one-carbon metabolism to support the methylation of multiple substrates including DNA. We aimed to test the hypothesis that folic acid supplementation alters DNA methylation profiles in AD models. Mouse Neuro-2a cells expressing human APP695 (N2a-APP cells) were incubated with folic acid (2.8-20 μmol/L). AD transgenic mice were fed either folate-deficient or control diets and gavaged daily with water or folic acid (600 μg/kg). Gene methylation profiles were determined by methylated DNA immunoprecipitation-DNA microarray (MeDIP-chip). Differentially methylated regions (DMRs) were determined by Quantitative Differentially Methylated Regions analysis, and differentially methylated genes (DMGs) carrying at least three DMRs were selected for pathway analysis. Folic acid up-regulated DNA methylation levels in N2a-APP cells and AD transgenic mouse brains. Functional network analysis of folic acid-induced DMGs in these AD models revealed subnetworks composed of 24 focus genes in the janus kinase-signal transducer and activator of transcription (JAK-STAT) signaling pathway and 12 focus genes in the long-term depression (LTD) signaling pathway. In conclusion, these results revealed a role for folic acid in the JAK-STAT and LTD signaling pathways which may be relevant to AD pathogenesis. This novel finding may stimulate reinvestigation of folic acid supplementation as a prophylactic or therapeutic treatment for AD.

  15. The effects of comorbidity in defining major depression subtypes associated with long-term course and severity

    PubMed Central

    Wardenaar, K. J.; van Loo, H. M.; Cai, T.; Fava, M.; Gruber, M. J.; Li, J.; de Jonge, P.; Nierenberg, A. A.; Petukhova, M. V.; Rose, S.; Sampson, N. A.; Schoevers, R. A.; Wilcox, M. A.; Alonso, J.; Bromet, E. J.; Bunting, B.; Florescu, S. E.; Fukao, A.; Gureje, O.; Hu, C.; Huang, Y. Q.; Karam, A. N.; Levinson, D.; Medina Mora, M. E.; Posada-Villa, J.; Scott, K. M.; Taib, N. I.; Viana, M. C.; Xavier, M.; Zarkov, Z.; Kessler, R. C.

    2014-01-01

    Background Although variation in long-term course of major depressive disorder (MDD) is not strongly predicted by existing symptom subtype distinctions, recent research suggests that prediction can be improved by using machine learning methods. However, it is not known whether these distinctions can be refined by added information about comorbid conditions. The current report presents results on this question. Methods Data come from 8,261 respondents with lifetime DSM-IV MDD in the WHO World Mental Health (WMH) Surveys. Outcomes include four retrospectively-reported measures of persistence-severity of course (years in episode; years in chronic episodes, hospitalization for MDD; disability due to MDD). Machine learning methods (regression tree analysis; lasso, ridge, and elastic net penalized regression) followed by k-means cluster analysis were used to augment previously-detected subtypes with information about prior comorbidity to predict these outcomes. Results Predicted values were strongly correlated across outcomes. Cluster analysis of predicted values found 3 clusters with consistently high, intermediate, or low values. The high-risk cluster (32.4% of cases) accounted for 56.6–72.9% of high persistence, high chronicity, hospitalization, and disability. This high-risk cluster had both higher sensitivity and likelihood-ratio positive (relative proportions of cases in the high-risk cluster versus other clusters having the adverse outcomes) than in a parallel analysis that excluded measures of comorbidity as predictors. Conclusions Although results using the retrospective data reported here suggest that useful MDD subtyping distinctions can be made with machine learning and clustering across multiple indicators of illness persistence-severity, replication is need with prospective data to confirm this preliminary conclusion. PMID:25066141

  16. Transcutaneous trigeminal nerve stimulation induces a long-term depression-like plasticity of the human blink reflex.

    PubMed

    Pilurzi, Giovanna; Mercante, Beniamina; Ginatempo, Francesca; Follesa, Paolo; Tolu, Eusebio; Deriu, Franca

    2016-02-01

    The beneficial effects of trigeminal nerve stimulation (TNS) on several neurological disorders are increasingly acknowledged. Hypothesized mechanisms include the modulation of excitability in networks involved by the disease, and its main site of action has been recently reported at brain stem level. Aim of this work was to test whether acute TNS modulates brain stem plasticity using the blink reflex (BR) as a model. The BR was recorded from 20 healthy volunteers before and after 20 min of cyclic transcutaneous TNS delivered bilaterally to the infraorbital nerve. Eleven subjects underwent sham-TNS administration and were compared to the real-TNS group. In 12 subjects, effects of unilateral TNS were tested. The areas of the R1 and R2 components of the BR were recorded before and after 0 (T0), 15 (T15), 30 (T30), and 45 (T45) min from TNS. In three subjects, T60 and T90 time points were also evaluated. Ipsi- and contralateral R2 areas were significantly suppressed after bilateral real-TNS at T15 (p = 0.013), T30 (p = 0.002), and T45 (p = 0.001), while R1 response appeared unaffected. The TNS-induced inhibitory effect on R2 responses lasted up to 60 min. Real- and sham-TNS protocols produced significantly different effects (p = 0.005), with sham-TNS being ineffective at any time point tested. Bilateral TNS was more effective (p = 0.009) than unilateral TNS. Acute TNS induced a bilateral long-lasting inhibition of the R2 component of the BR, which resembles a long-term depression-like effect, providing evidence of brain stem plasticity produced by transcutaneous TNS. These findings add new insight into mechanisms of TNS neuromodulation and into physiopathology of those neurological disorders where clinical benefits of TNS are recognized.

  17. X-ray enhancement and long-term evolution of swift J1822.3–1606

    SciTech Connect

    Benli, Onur; Çalışkan, Ş.; Ertan, Ü.; Alpar, M. A.; Trümper, J. E.; Kylafis, N. D.

    2013-12-01

    We investigate the X-ray enhancement and the long-term evolution of the recently discovered second 'low-B magnetar' Swift J1822.3-1606 in the frame of the fallback disk model. During a soft gamma burst episode, the inner disk matter is pushed back to larger radii, forming a density gradient at the inner disk. Subsequent relaxation of the inner disk could account for the observed X-ray enhancement light curve of Swift J1822.3-1606. We obtain model fits to the X-ray data with basic disk parameters similar to those employed to explain the X-ray outburst light curves of other anomalous X-ray pulsars and soft gamma repeaters. The long period (8.4 s) of the neutron star can be reached by the effect of the disk torques in the long-term accretion phase ((1-3) × 10{sup 5} yr). The currently ongoing X-ray enhancement could be due to a transient accretion epoch, or the source could still be in the accretion phase in quiescence. Considering these different possibilities, we determine the model curves that could represent the long-term rotational and the X-ray luminosity evolution of Swift J1822.3-1606, which constrain the strength of the magnetic dipole field to the range of (1-2) × 10{sup 12} G on the surface of the neutron star.

  18. Impact of sleep complaints and depression outcomes among participants in the standard medical intervention and long-term exercise study of exercise and pharmacotherapy for depression.

    PubMed

    Combs, Kory; Smith, Patrick J; Sherwood, Andrew; Hoffman, Benson; Carney, Robert M; Freedland, Kenneth; Craighead, W Edward; Blumenthal, James A

    2014-02-01

    The aim of this study was to examine the effects of exercise and sertraline on disordered sleep in patients with major depressive disorder (MDD). Methods The Standard Medical Intervention and Long-term Exercise study randomized the patients with MDD (n = 202) to one of four arms: a) supervised exercise, b) home-based exercise, c) sertraline therapy, and d) placebo pill. Sleep disturbance was assessed with three sleep-related items from the Hamilton Rating Scale for Depression (HAM-D) before and after 4 months of treatment. The patients were followed for 12 months to assess the prognostic value of sleep disturbance on MDD relapse and recovery.Results Comparison of the active treatment and placebo groups showed no treatment differences in HAM-D sleep complaints after 4 months (p = 0.758). However, residual insomnia symptoms after treatment were strongly associated with elevated depressive symptoms assessed by the HAM-D after 4 months (β = 0.342, p < 0.0001) and MDD relapse (odds ratio, 1.55; 95% confidence interval, 1.15-2.10; p = 0.004) assessed at 1-year follow-up (16 months after randomization). Neither exercise nor sertraline was associated with greater improvements in sleep disturbance compared with the placebo controls. However, residual symptoms of insomnia after successful treatment of MDD predicted relapse, highlighting the clinical importance of addressing insomnia in patients with MDD.

  19. Enhanced long-term organics and nitrogen removal and associated microbial community in intermittently aerated subsurface flow constructed wetlands.

    PubMed

    Fan, Jinlin; Zhang, Jian; Guo, Wenshan; Liang, Shuang; Wu, Haiming

    2016-08-01

    The long-term enhanced removal efficiency of organics and nitrogen in subsurface flow constructed wetlands (SSF CWs) with and without intermittent aeration for decentralized domestic wastewater was evaluated, and the function of intermittent aeration on microbial community was also investigated in this study. The high and long-term 95.6% COD, 96.1% NH4(+)-N and 85.8% TN removal efficiencies were achieved in experimental intermittently aerated SSF CW compared with non-aerated SSF CW. Aerated SSF CWs also exhibited the excellent removal performance when comparatively comparing with other strategies and techniques applied in CWs. In addition, fluorescence in situ hybridization (FISH) analysis revealed that associated microbial abundance significantly increased owing to intermittent aeration. These results indicated intermittent aeration CWs might be an effective and sustainable strategy for wastewater treatment in rural areas, but require further full-scale investigation in future.

  20. Enhanced Long Term Potentiation and Decreased AMPA Receptor Desensitization in the Acute Period Following a Single Kainate Induced Early Life Seizure

    PubMed Central

    O'Leary, Heather; Bernard, Paul B.; Castano, Anna M.; Benke, Tim A.

    2016-01-01

    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 ~50 days following kainic acid (KA) induced early life seizure (KA-ELS) in post-natal (P) 7 day 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 7 days, post KA-ELS. Our results show for the first time enhanced LTP 7 days after KA-ELS, but no change 2 days 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

  1. The relationship between trait vulnerability and anxiety and depressive diagnoses at long-term follow-up of Generalized Anxiety Disorder.

    PubMed

    Chambers, Julie A; Power, Kevin G; Durham, Robert C

    2004-01-01

    The current study examined the relationship between measures of trait vulnerability and long-term outcome in 83 patients diagnosed and treated for Generalized Anxiety Disorder (GAD) 8-14 years previously. Diagnostic status was assessed by structured interview, and trait affect, trait anxiety and trait depression were measured by the Positive and Negative Affect Scale (PANAS), the State-Trait Anxiety Inventory (STAI-T) and the Personal Style Inventory (PSI), respectively. Trait measures were all highly inter-correlated, and patients with diagnoses of GAD, social phobia and depressive disorders at long-term follow-up recorded very poor scores on all three scales. Trait anxiety recorded pre-treatment was also related to both anxiety and depression at long-term follow-up. However, trait depression showed no significant association with panic disorder. Increased numbers of comorbid diagnoses were strongly related to high levels of both trait anxiety and negative affect (NA). The findings suggest that patients reporting high trait anxiety or NA may suffer from a chronic course of disorder and higher levels of comorbidity over the longer term.

  2. Social support as a predictor of the outcome of depressive and anxiety disorder in short-term and long-term psychotherapy.

    PubMed

    Lindfors, Olavi; Ojanen, Sakari; Jääskeläinen, Tuija; Knekt, Paul

    2014-04-30

    Social support is known to be important for well-being of individuals, but it is not clear how it predicts psychotherapy outcome in patients suffering from depressive or anxiety disorders. The aim of the present study was to study the prediction of social support on the outcome of short-term and long-term psychotherapy. In the Helsinki Psychotherapy Study, 326 psychiatric outpatients, aged 20-46 years, and suffering from depressive or anxiety disorders, were randomly assigned to short-term psychotherapy (short-term psychodynamic or solution-focused) or long-term psychodynamic psychotherapy. The level of social support at baseline was assessed using the Brief Inventory of Social Support and Integration (BISSI). Psychiatric symptoms were assessed with the Symptom Check List, Global Severity Index (SCL-90-GSI) at baseline and four times during a 3-year follow-up. Patients with a high level of social support before treatment benefitted more from long-term than short-term therapy at the 3-year follow-up, whereas patients with a low level of social support experienced no such benefit. Pretreatment social support seems to predict differentially short- and long-term psychotherapy and thus needs to be acknowledged when evaluating patient's resources and treatment options. More research is needed to verify these findings.

  3. Service improvement system to enhance the safety of patients admitted on long-term warfarin

    PubMed Central

    Warcel, Dana; Johnson, Daniel; Shah, Neeraj; shreeve, Norman

    2014-01-01

    It is common for hospital inpatients on warfarin to suffer from fluctuations in their INR (international normalised ratio). Raised INRs are potentially very dangerous and may result in acute life-threatening haemorrhages. Conversely, low INRs may increase the risk for the development of venous thromboembolism. Having observed many deranged INRs among hospital inpatients, we decided to focus our project on identifying the contributing factors to deranged INRs and ways to address this problem. We analysed the warfarin prescriptions on all drug charts and surveyed the junior doctor staff. Our results revealed poor knowledge and confidence levels on warfarin prescribing among junior doctor staff. This is likely to be reflected in the poor completion rate of warfarin prescriptions. We instituted practical changes to resolve the issue: most importantly, a change to the warfarin administration time from 6 pm to 2 pm, supported by a poster campaign to increase awareness of the problem. The objective of these changes was to reduce prescribing errors by reducing warfarin prescriptions out-of-hours, by the on-call doctors. We repeated the audit cycle twice. Although our interventions were successfully introduced as shown in our second audit cycle, the changes that were implemented were not sustained as shown in the third audit cycle. We identified a need for annual intervention to educate new junior doctor staff to ensure that the positive outcomes achieved are maintained in the long term. PMID:26734259

  4. A Long-Term Performance Enhancement Method for FOG-Based Measurement While Drilling

    PubMed Central

    Zhang, Chunxi; Lin, Tie

    2016-01-01

    In the oil industry, the measurement-while-drilling (MWD) systems are usually used to provide the real-time position and orientation of the bottom hole assembly (BHA) during drilling. However, the present MWD systems based on magnetic surveying technology can barely ensure good performance because of magnetic interference phenomena. In this paper, a MWD surveying system based on a fiber optic gyroscope (FOG) was developed to replace the magnetic surveying system. To accommodate the size of the downhole drilling conditions, a new design method is adopted. In order to realize long-term and high position precision and orientation surveying, an integrated surveying algorithm is proposed based on inertial navigation system (INS) and drilling features. In addition, the FOG-based MWD error model is built and the drilling features are analyzed. The state-space system model and the observation updates model of the Kalman filter are built. To validate the availability and utility of the algorithm, the semi-physical simulation is conducted under laboratory conditions. The results comparison with the traditional algorithms show that the errors were suppressed and the measurement precision of the proposed algorithm is better than the traditional ones. In addition, the proposed method uses a lot less time than the zero velocity update (ZUPT) method. PMID:27483270

  5. A Long-Term Performance Enhancement Method for FOG-Based Measurement While Drilling.

    PubMed

    Zhang, Chunxi; Lin, Tie

    2016-07-28

    In the oil industry, the measurement-while-drilling (MWD) systems are usually used to provide the real-time position and orientation of the bottom hole assembly (BHA) during drilling. However, the present MWD systems based on magnetic surveying technology can barely ensure good performance because of magnetic interference phenomena. In this paper, a MWD surveying system based on a fiber optic gyroscope (FOG) was developed to replace the magnetic surveying system. To accommodate the size of the downhole drilling conditions, a new design method is adopted. In order to realize long-term and high position precision and orientation surveying, an integrated surveying algorithm is proposed based on inertial navigation system (INS) and drilling features. In addition, the FOG-based MWD error model is built and the drilling features are analyzed. The state-space system model and the observation updates model of the Kalman filter are built. To validate the availability and utility of the algorithm, the semi-physical simulation is conducted under laboratory conditions. The results comparison with the traditional algorithms show that the errors were suppressed and the measurement precision of the proposed algorithm is better than the traditional ones. In addition, the proposed method uses a lot less time than the zero velocity update (ZUPT) method.

  6. Hippocampal long-term depression is facilitated by the acquisition and updating of memory of spatial auditory content and requires mGlu5 activation.

    PubMed

    Dietz, Birte; Manahan-Vaughan, Denise

    2017-03-15

    Long-term potentiation (LTP) and long-term depression (LTD) are key cellular processes that support memory formation. Whereas increases of synaptic strength by means of LTP may support the creation of a spatial memory 'engram', LTD appears to play an important role in refining and optimising experience-dependent encoding. A differentiation in the role of hippocampal subfields is apparent. For example, LTD in the dentate gyrus (DG) is enabled by novel learning about large visuospatial features, whereas in area CA1, it is enabled by learning about discrete aspects of spatial content, whereby, both discrete visuospatial and olfactospatial cues trigger LTD in CA1. Here, we explored to what extent local audiospatial cues facilitate information encoding in the form of LTD in these subfields. Coupling of low frequency afferent stimulation (LFS) with discretely localised, novel auditory tones in the sonic hearing, or ultrasonic range, facilitated short-term depression (STD) into LTD (>24 h) in CA1, but not DG. Re-exposure to the now familiar audiospatial configuration ca. 1 week later failed to enhance STD. Reconfiguration of the same audiospatial cues resulted anew in LTD when ultrasound, but not non-ultrasound cues were used. LTD facilitation that was triggered by novel exposure to spatially arranged tones, or to spatial reconfiguration of the same tones were both prevented by an antagonism of the metabotropic glutamate receptor, mGlu5. These data indicate that, if behaviourally salient enough, the hippocampus can use audiospatial cues to facilitate LTD that contributes to the encoding and updating of spatial representations. Effects are subfield-specific, and require mGlu5 activation, as is the case for visuospatial information processing. These data reinforce the likelihood that LTD supports the encoding of spatial features, and that this occurs in a qualitative and subfield-specific manner. They also support that mGlu5 is essential for synaptic encoding of spatial

  7. Therapist-assisted, self-administered bibliotherapy to enhance parental competence: short- and long-term effects.

    PubMed

    Hahlweg, Kurt; Heinrichs, Nina; Kuschel, Annett; Feldmann, Marit

    2008-09-01

    The efficacy of bibliotherapy has primarily been investigated in anxiety disorders, depression, or substance dependence. The efficacy of self-help books to increase parenting competence was only investigated in a few studies despite their broad dissemination in public. The aims of the study were to investigate the short- and long-term efficacy of a therapist assisted version of the Triple P self-help booklet (Sanders, Markie-Dadds, & Turner, 2003) for families with preschool-age children in Germany. Sixty-nine families were randomly assigned to either a therapist-assisted self-administered parent training (SDPT+T) or to a waitlist control group (WL). Parents in the SDPT+T received the 10 chapter self-help book and an accompanying video. A Triple P facilitator offered seven telephone consultations which aimed to support parents in skill implementation. After the post test, the WL parents were also offered the intervention. A follow-up assessment was conducted six months after post. Compared to waitlist controls, SDPT+T mothers reported significant short- and long-term reductions in child behavior problems as well as in dysfunctional parenting practices. Fathers reported only marginal changes. The study adds further empirical support of parenting self-help materials.

  8. Tetraplegia is associated with enhanced peripheral chemoreflex sensitivity and ventilatory long-term facilitation.

    PubMed

    Sankari, Abdulghani; Bascom, Amy T; Riehani, Anas; Badr, M Safwan

    2015-11-15

    Cardiorespiratory plasticity induced by acute intermittent hypoxia (AIH) may contribute to recovery following spinal cord injury (SCI). We hypothesized that patients with cervical SCI would demonstrate higher minute ventilation (V̇e) following AIH compared with subjects with thoracic SCI and able-bodied subjects who served as controls. Twenty-four volunteers (8 with cervical SCI, 8 with thoracic SCI, and 8 able-bodied) underwent an AIH protocol during wakefulness. Each subject experienced 15 episodes of isocapnic hypoxia using mixed gases of 100% nitrogen (N2), 8% O2, and 40% CO2 to achieve oxygen saturation ≤90% followed by room air (RA). Measurements were obtained before, during, and 40 min after AIH to obtain ventilation and heart rate variability data [R-R interval (RRI) and low-frequency/high-frequency power (LF/HF)]. AIH results were compared with those of sham studies conducted in RA during the same time period. Individuals with cervical SCI had higher V̇e after AIH compared with able-bodied controls (117.9 ± 23.2% vs. 97.9 ± 11.2%, P < 0.05). RRI decreased during hypoxia in all individuals (those with cervical SCI, from 1,009.3 ± 65.0 ms to 750.2 ± 65.0 ms; those with thoracic SCI, from 945.2 ± 65.0 ms to 674.9 ± 65.0 ms; and those who were able-bodied, from 949 ± 75.0 to 682.2 ± 69.5 ms; P < 0.05). LH/HF increased during recovery in individuals with thoracic SCI and those who were able-bodied (0.54 ± 0.22 vs. 1.34 ± 0.22 and 0.67 ± 0.23 vs. 1.82 ± 0.23, respectively; P < 0.05) but remained unchanged in the group with cervical SCI. Our conclusion is that patients with cervical SCI demonstrate ventilatory long-term facilitation following AIH compared with able-bodied controls. Heart rate responses to hypoxia are acutely present in patients with cervical SCI but are absent during posthypoxic recovery.

  9. Muscarinic Long-Term Enhancement of Tonic and Phasic GABAA Inhibition in Rat CA1 Pyramidal Neurons.

    PubMed

    Domínguez, Soledad; Fernández de Sevilla, David; Buño, Washington

    2016-01-01

    Acetylcholine (ACh) regulates network operation in the hippocampus by controlling excitation and inhibition in rat CA1 pyramidal neurons (PCs), the latter through gamma-aminobutyric acid type-A receptors (GABA A Rs). Although, the enhancing effects of ACh on GABA A Rs have been reported (Dominguez et al., 2014, 2015), its role in regulating tonic GABAA inhibition has not been explored in depth. Therefore, we aimed at determining the effects of the activation of ACh receptors on responses mediated by synaptic and extrasynaptic GABAARs. Here, we show that under blockade of ionotropic glutamate receptors ACh, acting through muscarinic type 1 receptors, paired with post-synaptic depolarization induced a long-term enhancement of tonic GABA A currents ( t GABA A ) and puff-evoked GABA A currents ( p GABAA). ACh combined with depolarization also potentiated IPSCs (i.e., phasic inhibition) in the same PCs, without signs of interactions of synaptic responses with p GABAA and t GABAA, suggesting the contribution of two different GABAA receptor pools. The long-term enhancement of GABAA currents and IPSCs reduced the excitability of PCs, possibly regulating plasticity and learning in behaving animals.

  10. Muscarinic Long-Term Enhancement of Tonic and Phasic GABAA Inhibition in Rat CA1 Pyramidal Neurons

    PubMed Central

    Domínguez, Soledad; Fernández de Sevilla, David; Buño, Washington

    2016-01-01

    Acetylcholine (ACh) regulates network operation in the hippocampus by controlling excitation and inhibition in rat CA1 pyramidal neurons (PCs), the latter through gamma-aminobutyric acid type-A receptors (GABAARs). Although, the enhancing effects of ACh on GABAARs have been reported (Dominguez et al., 2014, 2015), its role in regulating tonic GABAA inhibition has not been explored in depth. Therefore, we aimed at determining the effects of the activation of ACh receptors on responses mediated by synaptic and extrasynaptic GABAARs. Here, we show that under blockade of ionotropic glutamate receptors ACh, acting through muscarinic type 1 receptors, paired with post-synaptic depolarization induced a long-term enhancement of tonic GABAA currents (tGABAA) and puff-evoked GABAA currents (pGABAA). ACh combined with depolarization also potentiated IPSCs (i.e., phasic inhibition) in the same PCs, without signs of interactions of synaptic responses with pGABAA and tGABAA, suggesting the contribution of two different GABAA receptor pools. The long-term enhancement of GABAA currents and IPSCs reduced the excitability of PCs, possibly regulating plasticity and learning in behaving animals. PMID:27833531

  11. Increasing cellular level of phosphatidic acid enhances FGF-1 production in long term-cultured rat astrocytes.

    PubMed

    Nagayasu, Yuko; Morita, Shin-Ya; Hayashi, Hideki; Miura, Yutaka; Yokoyama, Kazuki; Michikawa, Makoto; Ito, Jin-Ichi

    2014-05-14

    We found in a previous study that both mRNA expression and release of fibroblast growth factor 1 (FGF-1) are greater in rat astrocytes that are long term-cultured for one month (W/M cells) than in the cells cultured for one week (W/W cells). However, FGF-1 does not enhance phosphorylation of Akt, MEK, and ERK in W/M cells, while it does in W/W cells. In this work we studied the mechanism to cause these differences between W/W and W/M cells in culture. As it is known that long term culture generates oxidative stress, we characterized the stresses which W/M cells undergo in comparison with W/W cells. The levels of superoxide dismutase 1 (SOD1) and mitochondrial Bax were higher in W/M cells than in W/W cells. W/M cells recovered their ability to respond to FGF-1 to enhance phosphorylation of Akt, MEK, and ERK in the presence of antioxidants. Oxidative stress induced by hydrogen peroxide (H2O2) had no effect on mRNA expression of FGF-1 in W/W cells, although H2O2 enhances release of FGF-1 from W/W cells without inducing apoptosis. The influence of cell density was studied on mRNA expression of FGF-1 and cellular response to FGF-1, as an increasing cell density is observed in W/M cells. The increasing cell density enhanced mRNA expression of FGF-1 in W/W cells without suppression of responses to FGF-1. The decrease in cell density lowered the FGF-1 mRNA expression in W/M cells without recovery of the response to FGF-1 to enhance phosphorylation of Akt, MEK, and ERK. These findings suggest that oxidative stress attenuate sensitivity to FGF-1 and higher cell density may enhance FGF-1 expression in W/M cells. In addition, we found that the cellular level of phosphatidic acid (PA) increased in H2O2-treated W/W and W/M cells and decreased by the treatment with antioxidants, and that PA enhances the mRNA expression of FGF-1 in the W/W cells. These findings suggest that the increasing PA production may enhance FGF-1 expression to protect astrocytes against oxidative stress

  12. Acutely applied MDMA enhances long-term potentiation in rat hippocampus involving D1/D5 and 5-HT2 receptors through a polysynaptic mechanism.

    PubMed

    Rozas, C; Loyola, S; Ugarte, G; Zeise, M L; Reyes-Parada, M; Pancetti, F; Rojas, P; Morales, B

    2012-08-01

    3,4-Methylenedioxymethamphetamine (MDMA, ecstasy) is a drug of abuse that induces learning and memory deficit. However, there are no experimental data that correlate the behavioral evidence with models of synaptic plasticity such as long-term potentiation (LTP) or long-term depression (LTD). Using field potential recordings in rat hippocampal slices of young rats, we found that acute application of MDMA enhances LTP in CA3-CA1 synapses without affecting LTD. Using specific antagonists and paired-pulse facilitation protocols we observed that the MDMA-dependent increase of LTP involves presynaptic 5-HT₂ serotonin receptors and postsynaptic D1/D5 dopamine receptors. In addition, the inhibition of PKA suppresses the MDMA-dependent increase in LTP, suggesting that dopamine receptor agonism activates cAMP-dependent intracellular pathways. We propose that MDMA exerts its LTP-altering effect involving a polysynaptic interaction between serotonergic and dopaminergic systems in hippocampal synapses. Our results are compatible with the view that the alterations in hippocampal LTP could be responsible for MDMA-dependent cognitive deficits observed in humans and animals.

  13. Consolidation power of extrinsic rewards: reward cues enhance long-term memory for irrelevant past events.

    PubMed

    Murayama, Kou; Kitagami, Shinji

    2014-02-01

    Recent research suggests that extrinsic rewards promote memory consolidation through dopaminergic modulation processes. However, no conclusive behavioral evidence exists given that the influence of extrinsic reward on attention and motivation during encoding and consolidation processes are inherently confounded. The present study provides behavioral evidence that extrinsic rewards (i.e., monetary incentives) enhance human memory consolidation independently of attention and motivation. Participants saw neutral pictures, followed by a reward or control cue in an unrelated context. Our results (and a direct replication study) demonstrated that the reward cue predicted a retrograde enhancement of memory for the preceding neutral pictures. This retrograde effect was observed only after a delay, not immediately upon testing. An additional experiment showed that emotional arousal or unconscious resource mobilization cannot explain the retrograde enhancement effect. These results provide support for the notion that the dopaminergic memory consolidation effect can result from extrinsic reward.

  14. Combining brain stimulation and video game to promote long-term transfer of learning and cognitive enhancement

    PubMed Central

    Looi, Chung Yen; Duta, Mihaela; Brem, Anna-Katharine; Huber, Stefan; Nuerk, Hans-Christoph; Cohen Kadosh, Roi

    2016-01-01

    Cognitive training offers the potential for individualised learning, prevention of cognitive decline, and rehabilitation. However, key research challenges include ecological validity (training design), transfer of learning and long-term effects. Given that cognitive training and neuromodulation affect neuroplasticity, their combination could promote greater, synergistic effects. We investigated whether combining transcranial direct current stimulation (tDCS) with cognitive training could further enhance cognitive performance compared to training alone, and promote transfer within a short period of time. Healthy adults received real or sham tDCS over their dorsolateral prefrontal cortices during two 30-minute mathematics training sessions involving body movements. To examine the role of training, an active control group received tDCS during a non-mathematical task. Those who received real tDCS performed significantly better in the game than the sham group, and showed transfer effects to working memory, a related but non-numerical cognitive domain. This transfer effect was absent in active and sham control groups. Furthermore, training gains were more pronounced amongst those with lower baseline cognitive abilities, suggesting the potential for reducing cognitive inequalities. All effects associated with real tDCS remained 2 months post-training. Our study demonstrates the potential benefit of this approach for long-term enhancement of human learning and cognition. PMID:26902664

  15. Post-learning stress enhances long-term memory and differentially influences memory in females depending on menstrual stage.

    PubMed

    Zoladz, Phillip R; Peters, David M; Cadle, Chelsea E; Kalchik, Andrea E; Aufdenkampe, Rachael L; Dailey, Alison M; Brown, Callie M; Scharf, Amanda R; Earley, McKenna B; Knippen, Courtney L; Rorabaugh, Boyd R

    2015-09-01

    Most work has shown that post-learning stress enhances long-term memory; however, there have been recent inconsistencies in this literature. The purpose of the present study was to examine further the effects of post-learning stress on long-term memory and to explore any sex differences that may exist. Male and female participants learned a list of 42 words that varied in emotional valence and arousal level. Following encoding, participants completed a free recall assessment and then submerged their hand into a bath of ice cold (stress) or lukewarm (no stress) water for 3 min. The next day, participants were given free recall and recognition tests. Stressed participants recalled more words than non-stressed participants 24h after learning. Stress also enhanced female participants' recall of arousing words when they were in the follicular, but not luteal, phase. These findings replicate previous work examining post-learning stress effects on memory and implicate the involvement of sex-related hormones in such effects.

  16. Safety of real-time convection-enhanced delivery of liposomes to primate brain: a long-term retrospective

    PubMed Central

    Krauze, Michal T.; Vandenberg, Scott R.; Yamashita, Yoji; Saito, Ryuta; Forsayeth, John; Noble, Charles; Park, John; Bankiewicz, Krystof S.

    2008-01-01

    Convection-enhanced delivery (CED) is gaining popularity in direct brain infusions. Our group has pioneered the use of liposomes loaded with the MRI contrast reagent as a means to track and quantitate CED in the primate brain through real-time MRI. When co-infused with therapeutic nanoparticles, these tracking liposomes provide us with unprecedented precision in the management of infusions into discrete brain regions. In order to translate real-time CED into clinical application, several important parameters must be defined. In this study, we have analyzed all our cumulative animal data to answer a number of questions as to whether real-time CED in primates depends on concentration of infusate, is reproducible, allows prediction of distribution in a given anatomic structure, and whether it has long term pathological consequences. Our retrospective analysis indicates that real-time CED is highly predictable; repeated procedures yielded identical results, and no long-term brain pathologies were found. We conclude that introduction of our technique to clinical application would enhance accuracy and patient safety when compared to current non-monitored delivery trials. PMID:18295759

  17. Safety of real-time convection-enhanced delivery of liposomes to primate brain: a long-term retrospective.

    PubMed

    Krauze, Michal T; Vandenberg, Scott R; Yamashita, Yoji; Saito, Ryuta; Forsayeth, John; Noble, Charles; Park, John; Bankiewicz, Krystof S

    2008-04-01

    Convection-enhanced delivery (CED) is gaining popularity in direct brain infusions. Our group has pioneered the use of liposomes loaded with the MRI contrast reagent as a means to track and quantitate CED in the primate brain through real-time MRI. When co-infused with therapeutic nanoparticles, these tracking liposomes provide us with unprecedented precision in the management of infusions into discrete brain regions. In order to translate real-time CED into clinical application, several important parameters must be defined. In this study, we have analyzed all our cumulative animal data to answer a number of questions as to whether real-time CED in primates depends on concentration of infusate, is reproducible, allows prediction of distribution in a given anatomic structure, and whether it has long term pathological consequences. Our retrospective analysis indicates that real-time CED is highly predictable; repeated procedures yielded identical results, and no long-term brain pathologies were found. We conclude that introduction of our technique to clinical application would enhance accuracy and patient safety when compared to current non-monitored delivery trials.

  18. Combining brain stimulation and video game to promote long-term transfer of learning and cognitive enhancement.

    PubMed

    Looi, Chung Yen; Duta, Mihaela; Brem, Anna-Katharine; Huber, Stefan; Nuerk, Hans-Christoph; Cohen Kadosh, Roi

    2016-02-23

    Cognitive training offers the potential for individualised learning, prevention of cognitive decline, and rehabilitation. However, key research challenges include ecological validity (training design), transfer of learning and long-term effects. Given that cognitive training and neuromodulation affect neuroplasticity, their combination could promote greater, synergistic effects. We investigated whether combining transcranial direct current stimulation (tDCS) with cognitive training could further enhance cognitive performance compared to training alone, and promote transfer within a short period of time. Healthy adults received real or sham tDCS over their dorsolateral prefrontal cortices during two 30-minute mathematics training sessions involving body movements. To examine the role of training, an active control group received tDCS during a non-mathematical task. Those who received real tDCS performed significantly better in the game than the sham group, and showed transfer effects to working memory, a related but non-numerical cognitive domain. This transfer effect was absent in active and sham control groups. Furthermore, training gains were more pronounced amongst those with lower baseline cognitive abilities, suggesting the potential for reducing cognitive inequalities. All effects associated with real tDCS remained 2 months post-training. Our study demonstrates the potential benefit of this approach for long-term enhancement of human learning and cognition.

  19. Enhancing dopaminergic signaling and histone acetylation promotes long-term rescue of deficient fear extinction

    PubMed Central

    Whittle, N; Maurer, V; Murphy, C; Rainer, J; Bindreither, D; Hauschild, M; Scharinger, A; Oberhauser, M; Keil, T; Brehm, C; Valovka, T; Striessnig, J; Singewald, N

    2016-01-01

    Extinction-based exposure therapy is used to treat anxiety- and trauma-related disorders; however, there is the need to improve its limited efficacy in individuals with impaired fear extinction learning and to promote greater protection against return-of-fear phenomena. Here, using 129S1/SvImJ mice, which display impaired fear extinction acquisition and extinction consolidation, we revealed that persistent and context-independent rescue of deficient fear extinction in these mice was associated with enhanced expression of dopamine-related genes, such as dopamine D1 (Drd1a) and -D2 (Drd2) receptor genes in the medial prefrontal cortex (mPFC) and amygdala, but not hippocampus. Moreover, enhanced histone acetylation was observed in the promoter of the extinction-regulated Drd2 gene in the mPFC, revealing a potential gene-regulatory mechanism. Although enhancing histone acetylation, via administering the histone deacetylase (HDAC) inhibitor MS-275, does not induce fear reduction during extinction training, it promoted enduring and context-independent rescue of deficient fear extinction consolidation/retrieval once extinction learning was initiated as shown following a mild conditioning protocol. This was associated with enhanced histone acetylation in neurons of the mPFC and amygdala. Finally, as a proof-of-principle, mimicking enhanced dopaminergic signaling by L-dopa treatment rescued deficient fear extinction and co-administration of MS-275 rendered this effect enduring and context-independent. In summary, current data reveal that combining dopaminergic and epigenetic mechanisms is a promising strategy to improve exposure-based behavior therapy in extinction-impaired individuals by initiating the formation of an enduring and context-independent fear-inhibitory memory. PMID:27922638

  20. Long-term effects of St. John's wort (Hypericum perforatum) treatment: a 1-year safety study in mild to moderate depression.

    PubMed

    Brattström, Axel

    2009-04-01

    Long-term safety and the effects of a St. John's wort (SJW) extract Ze 117 (Hypericum perforatum) were evaluated in the treatment of patients with depression. An open multicentre safety study with 440 out-patients suffering from mild to moderate depression according to ICD-10 was conducted. Patients were treated for up to 1 year with 500 mg St. John's wort extract per day (Ze 117). Evaluation criteria were safety (adverse event frequency) and influence on depression (HAM-D, CGI). Two hundred and seventeen (49%) patients reported 504 adverse events, 30 (6%) of which were possibly or probably related to the treatment. Gastrointestinal and skin complaints were the most common events associated with treatment. No age-related difference in the safety of the applied medication was found. The long-term intake of up to 1 year of the study medication did not result in any changes in clinical chemistry and electrocardiogram recordings. Body mass index (BMI) did not change either. Mean HAM-D scores decreased steadily from 20.58 at baseline to 12.07 at week 26 and to 11.18 at week 52. Mean CGI scores decreased from 3.99 to 2.20 at week 26 and 2.19 at week 52. Therefore, St. John's wort extract ZE 117 is a safe and effective way to treat mild to moderate depression over long periods of time, and therefore seems especially suitable for a relapse prevention.

  1. Long-Term Corticosterone Exposure Decreases Insulin Sensitivity and Induces Depressive-Like Behaviour in the C57BL/6NCrl Mouse

    PubMed Central

    van Donkelaar, Eva L.; Vaessen, Koen R. D.; Pawluski, Jodi L.; Sierksma, Annerieke S.; Blokland, Arjan; Cañete, Ramón; Steinbusch, Harry W. M.

    2014-01-01

    Chronic stress or long-term administration of glucocorticoids disrupts the hypothalamus-pituitary-adrenal system leading to continuous high levels of glucocorticoids and insulin resistance (IR). This pre-diabetic state can eventually develop into type 2 diabetes mellitus and has been associated with a higher risk to develop depressive disorders. The mechanisms underlying the link between chronic stress, IR and depression remains unclear. The present study aimed to establish a stress-depression model in mice to further study the effects of stress-induced changes upon insulin sensitivity and behavioural consequences. A pilot study was conducted to establish the optimal administration route and a pragmatic measurement of IR. Subsequently, 6-month-old C57BL/6NCrl mice were exposed to long-term oral corticosterone treatment via the drinking water. To evaluate insulin sensitivity changes, blood glucose and plasma insulin levels were measured at different time-points throughout treatment and mice were behaviourally assessed in the elevated zero maze (EZM), forced swimming test (FST) and open field test to reveal behavioural changes. Long-term corticosterone treatment increased body weight and decreased insulin sensitivity. The latter was revealed by a higher IR index and increased insulin in the plasma, whereas blood glucose levels remained unchanged. Corticosterone treatment induced longer immobility times in the FST, reflecting depressive-like behaviour. No effects were observed upon anxiety as measured in the EZM. The effect of the higher body weight of the CORT treated animals at time of testing did not influence behaviour in the EZM or FST, as no differences were found in general locomotor activity. Long-term corticosterone treatment via the drinking water reduces insulin sensitivity and induces depressive-like behaviour in the C57BL/6 mouse. This mouse model could thus be used to further explore the underlying mechanisms of chronic stress-induced T2DM and its

  2. Long-term corticosterone exposure decreases insulin sensitivity and induces depressive-like behaviour in the C57BL/6NCrl mouse.

    PubMed

    van Donkelaar, Eva L; Vaessen, Koen R D; Pawluski, Jodi L; Sierksma, Annerieke S; Blokland, Arjan; Cañete, Ramón; Steinbusch, Harry W M

    2014-01-01

    Chronic stress or long-term administration of glucocorticoids disrupts the hypothalamus-pituitary-adrenal system leading to continuous high levels of glucocorticoids and insulin resistance (IR). This pre-diabetic state can eventually develop into type 2 diabetes mellitus and has been associated with a higher risk to develop depressive disorders. The mechanisms underlying the link between chronic stress, IR and depression remains unclear. The present study aimed to establish a stress-depression model in mice to further study the effects of stress-induced changes upon insulin sensitivity and behavioural consequences. A pilot study was conducted to establish the optimal administration route and a pragmatic measurement of IR. Subsequently, 6-month-old C57BL/6NCrl mice were exposed to long-term oral corticosterone treatment via the drinking water. To evaluate insulin sensitivity changes, blood glucose and plasma insulin levels were measured at different time-points throughout treatment and mice were behaviourally assessed in the elevated zero maze (EZM), forced swimming test (FST) and open field test to reveal behavioural changes. Long-term corticosterone treatment increased body weight and decreased insulin sensitivity. The latter was revealed by a higher IR index and increased insulin in the plasma, whereas blood glucose levels remained unchanged. Corticosterone treatment induced longer immobility times in the FST, reflecting depressive-like behaviour. No effects were observed upon anxiety as measured in the EZM. The effect of the higher body weight of the CORT treated animals at time of testing did not influence behaviour in the EZM or FST, as no differences were found in general locomotor activity. Long-term corticosterone treatment via the drinking water reduces insulin sensitivity and induces depressive-like behaviour in the C57BL/6 mouse. This mouse model could thus be used to further explore the underlying mechanisms of chronic stress-induced T2DM and its

  3. 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.

  4. Comparative effectiveness of exercise with patterned sensory enhanced music and background music for long-term care residents.

    PubMed

    O'Konski, Marjorie; Bane, Cynthia; Hettinga, Johanna; Krull, Katelyn

    2010-01-01

    The current study compared exercise performance and participant satisfaction for 2 conditions: Patterned Sensory Enhanced music (PSE) and big band background music. Residents of long-term care facilities in the Midwest (N = 45) attended a minimum of 3 sessions per condition and reported levels of satisfaction after each session. Observers blind to condition coded videotapes for number of repetitions, adherence to modeled movements, range of motion, and form. Significant differences were found for only 3/19 exercises and satisfaction levels did not differ between the 2 conditions. The results indicate that PSE may not be more effective than big band background music but that both types of music enhance exercise performance and participant enjoyment. PSE also provides consistency in number of repetitions led.

  5. Distinctiveness enhances long-term event memory in non-human primates, irrespective of reinforcement.

    PubMed

    Lewis, Amy; Call, Josep; Berntsen, Dorthe

    2017-04-13

    Non-human primates are capable of recalling events that occurred as long as 3 years ago, and are able to distinguish between similar events; akin to human memory. In humans, distinctiveness enhances memory for events, however, it is unknown whether the same occurs in non-human primates. As such, we tested three great ape species on their ability to remember an event that varied in distinctiveness. Across three experiments, apes witnessed a baiting event in which one of three identical containers was baited with food. After a delay of 2 weeks, we tested their memory for the location of the baited container. Apes failed to recall the baited container when the event was undistinctive (Experiment 1), but were successful when it was distinctive (Experiment 2), although performance was equally good in a less-distinctive condition. A third experiment (Experiment 3) confirmed that distinctiveness, independent of reinforcement, was a consistent predictor of performance. These findings suggest that distinctiveness may enhance memory for events in non-human primates in the same way as in humans, and provides further evidence of basic similarities between the ways apes and humans remember past events.

  6. Prolonged ampakine exposure prunes dendritic spines and increases presynaptic release probability for enhanced long-term potentiation in the hippocampus.

    PubMed

    Chang, Philip K-Y; Prenosil, George A; Verbich, David; Gill, Raminder; McKinney, R Anne

    2014-09-01

    CX 546, an allosteric positive modulator of α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid-type ionotropic glutamate receptors (AMPARs), belongs to a drug class called ampakines. These compounds have been shown to enhance long-term potentiation (LTP), a cellular model of learning and memory, and improve animal learning task performance, and have augmented cognition in neurodegenerative patients. However, the chronic effect of CX546 on synaptic structures has not been examined. The structure and integrity of dendritic spines are thought to play a role in learning and memory, and their abnormalities have been implicated in cognitive disorders. In addition, their structural plasticity has been shown to be important for cognitive function, such that dendritic spine remodeling has been proposed as the morphological correlate for LTP. Here, we tested the effect of CX546 on dendritic spine remodeling following long-term treatment. We found that, with prolonged CX546 treatment, organotypic hippocampal slice cultures showed a significant reduction in CA3-CA1 excitatory synapse and spine density. Electrophysiological approaches revealed that the CA3-CA1 circuitry compensates for this synapse loss by increasing synaptic efficacy through enhancement of presynaptic release probability. CX546-treated slices showed prolonged and enhanced potentiation upon LTP induction. Furthermore, structural plasticity, namely spine head enlargement, was also more pronounced after CX546 treatment. Our results suggest a concordance of functional and structural changes that is enhanced with prolonged CX546 exposure. Thus, the improved cognitive ability of patients receiving ampakine treatment may result from the priming of synapses through increases in the structural plasticity and functional reliability of hippocampal synapses.

  7. Daily cognitive appraisals, daily affect, and long-term depressive symptoms: the role of self-esteem and self-concept clarity in the stress process.

    PubMed

    Lee-Flynn, Sharon C; Pomaki, Georgia; Delongis, Anita; Biesanz, Jeremy C; Puterman, Eli

    2011-02-01

    The current study investigated how self-esteem and self-concept clarity are implicated in the stress process both in the short and long term. Initial and 2-year follow-up interviews were completed by 178 participants from stepfamily unions. In twice-daily structured diaries over 7 days, participants reported their main family stressor, cognitive appraisals (perceived stressor threat and stressor controllability), and negative affect. Results of multilevel modeling indicated that high self-esteem ameliorated the effect of daily negative cognitive appraisals on daily negative affect. Self-concept clarity also buffered the effect of low self-self-esteem on depressive symptoms 2 years later. Our findings point to the vulnerability of those having low self-esteem or low self-concept clarity in terms of both short- and long-term adaptation to stress. They indicate the need for the consideration of such individual differences in designing stress management interventions.

  8. Maternal lead exposure produces long-term enhancement of dopaminergic reactivity in rat offspring.

    PubMed

    Szczerbak, Grazyna; Nowak, Przemysław; Kostrzewa, Richard M; Brus, Ryszard

    2007-10-01

    To determine the effect of prenatal lead exposure on brain monoaminergic systems, pregnant rats were given tap water containing 250 ppm lead acetate, for the duration of pregnancy, while tap water without lead (Pb(2+)) was substituted at birth. Control rats were derived from dams that consumed tap water during pregnancy, and had no exposure to lead afterwards. At 12 weeks after birth, Pb(2+) content of brain cortex was increased 3- to 4-fold (P < 0.05). At this time the endogenous striatal levels of 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid were 19% lower in Pb(2+) exposed rats (P < 0.05), while there was no change in the striatal level of dopamine (DA), noradrenaline, 3,4-dihydroxyphenylglycol, serotonin (5-HT) and 5-hydroxyindoleacetic acid (HPLC/ED). Also there was no change in these monoamines and metabolites in the prefrontal cortex of Pb(2+) exposed rats. However, turnover of 5-HT in prefrontal cortex, as indicated by 5-hydroxytryptophan accumulation 30 min after acute treatment with the decarboxylase inhibitor NSD-1015 (100 mg/kg IP), was lower in the Pb(2+) exposed rats. In the striatum AMPH-induced (1 mg/kg IP) turnover of DA, evidenced as L-DOPA accumulation after NSD-1015, was increased to a lesser extent in the Pb(2+) exposed rats (P < 0.05). The nitric oxide synthase inhibitor 7-nitroindazole (10 mg/kg IP) attenuated the latter effect, indicating that neuronal NO mediates this AMPH effect, at least in part. Moreover, DA D(2) receptor sensitivity developed in Pb(2+) exposed rats, as evidenced by enhanced quinpirole-induced yawning activity and enhanced quinpirole-induced locomotor activity (each, P < 0.05). These findings indicate that ontogenetic exposure to lead can have consequences on monoaminergic neuronal function at an adult stage of life, generally promoting accentuated behavioral effects of direct and indirect monoaminergic agonists, and related to increased dopamine turnover in basal ganglia.

  9. Remission and Recovery in the Treatment for Adolescents with Depression Study (TADS): Acute and Long-Term Outcomes

    ERIC Educational Resources Information Center

    Kennard, Betsy D.; Silva, Susan G.; Tonev, Simon; Rohde, Paul; Hughes, Jennifer L.; Vitiello, Benedetto; Kratochvil, Christopher J.; Curry, John F.; Emslie, Graham J.; Reinecke, Mark; March, John

    2009-01-01

    The remission and recovery rates of adolescent patients with depression who were treated with fluoxetine, cognitive-behavioral therapy, their combination, and placebos were examined through a multisite clinical trial. It is concluded that most depressed adolescents who received such therapies achieved remission at the end of nine months.

  10. Urease immobilized polymer hydrogel: Long-term stability and enhancement of enzymatic activity.

    PubMed

    Kutcherlapati, S N Raju; Yeole, Niranjan; Jana, Tushar

    2016-02-01

    A method has been developed in which an enzyme namely urease was immobilized inside hydrogel matrix to study the stability and enzymatic activity in room temperature (∼27-30°C). This urease coupled hydrogel (UCG) was obtained by amine-acid coupling reaction and this procedure is such that it ensured the wider opening of mobile flap of enzyme active site. A systematic comparison of urea-urease assay and the detailed kinetic data clearly revealed that the urease shows activity for more than a month when stored at ∼27-30°C in case of UCG whereas it becomes inactive in case of free urease (enzyme in buffer solution). The aqueous microenvironment inside the hydrogel, unusual morphological features and thermal behaviour were believed to be the reasons for unexpected behaviour. UCG displayed enzyme activity at basic pH and up to 60°C. UCG showed significant enhancement in activity against thermal degradation compared to free urease. In summary, this method is a suitable process to stabilize the biomacromolecules in standard room temperature for many practical uses.

  11. Liposomal glucocorticosteroids in treatment of chronic autoimmune demyelination: long-term protective effects and enhanced efficacy of methylprednisolone formulations.

    PubMed

    Linker, Ralf A; Weller, Charlotte; Lühder, Fred; Mohr, Alexander; Schmidt, Jens; Knauth, Michael; Metselaar, Josbert M; Gold, Ralf

    2008-06-01

    Liposomal encapsulation leads to enhanced efficacy of glucocorticosteroids (GS) in treatment of autoimmune diseases. Here we compare liposomal prednisolone (PL) to liposomal methylprednisolone (MPL) in chronic-relapsing myelin oligodendrocyte glycoprotein-induced experimental autoimmune encephalomyelitis (EAE), a model closely reflecting aspects of multiple sclerosis (MS). At the maximum of the first relapse, a single dose of PL or MPL was applied at 10 mg/kg or at 4 mg/kg and compared to classical methylprednisolone (MP) pulse therapy. PL at 10 mg/kg was superior to free MP with long-term efficacy and a sustained protection even during the second and third relapse. At the same time, in vivo magnetic resonance imaging of rat brains revealed a significant reduction of T2-lesions after PL application. Comparison of PL and MPL at 10 mg/kg disclosed superior effects for MPL with an enhanced reduction of inflammatory infiltration as well as preservation of myelin and axons. Dose titration experiments underscored a dose-dependent efficacy of liposomal GS with a sustained efficacy especially of the higher dosage. In histological analyses, PL10 was superior in reducing macrophage and T cell infiltration as well as demyelination and axonal loss while the lower dosages were still at least as effective as free MP. FACS analyses revealed an effect of liposome formulations on T cell numbers, the CD4/CD8 ratio, frequencies of regulatory T cells and adhesion molecule expression. In summary, liposomal GS and especially methylprednisolone formulations display an enhanced efficacy not only in acute inflammatory, but also in chronic demyelinating models of MS and confer long-term protection from relapses. These findings lay the groundwork for applying liposomal GS in clinical MS trials in the near future.

  12. Stimulus uncertainty enhances long-term potentiation-like plasticity in human motor cortex.

    PubMed

    Sale, Martin V; Nydam, Abbey S; Mattingley, Jason B

    2017-03-01

    Plasticity can be induced in human cortex using paired associative stimulation (PAS), which repeatedly and predictably pairs a peripheral electrical stimulus with transcranial magnetic stimulation (TMS) to the contralateral motor region. Many studies have reported small or inconsistent effects of PAS. Given that uncertain stimuli can promote learning, the predictable nature of the stimulation in conventional PAS paradigms might serve to attenuate plasticity induction. Here, we introduced stimulus uncertainty into the PAS paradigm to investigate if it can boost plasticity induction. Across two experimental sessions, participants (n = 28) received a modified PAS paradigm consisting of a random combination of 90 paired stimuli and 90 unpaired (TMS-only) stimuli. Prior to each of these stimuli, participants also received an auditory cue which either reliably predicted whether the upcoming stimulus was paired or unpaired (no uncertainty condition) or did not predict the upcoming stimulus (maximum uncertainty condition). Motor evoked potentials (MEPs) evoked from abductor pollicis brevis (APB) muscle quantified cortical excitability before and after PAS. MEP amplitude increased significantly 15 min following PAS in the maximum uncertainty condition. There was no reliable change in MEP amplitude in the no uncertainty condition, nor between post-PAS MEP amplitudes across the two conditions. These results suggest that stimulus uncertainty may provide a novel means to enhance plasticity induction with the PAS paradigm in human motor cortex. To provide further support to the notion that stimulus uncertainty and prediction error promote plasticity, future studies should further explore the time course of these changes, and investigate what aspects of stimulus uncertainty are critical in boosting plasticity.

  13. Gender differences in the long-term associations between post-traumatic stress disorder and depression symptoms: Findings from the Detroit Neighborhood Health Study

    PubMed Central

    Horesh, Danny; Lowe, Sarah R.; Galea, Sandro; Uddin, Monica; Koenen, Karestan C.

    2014-01-01

    Objective Post-traumatic stress disorder (PTSD) and depression are known to be highly co-morbid. However, previous findings regarding the nature of this co-morbidity have been inconclusive. This study prospectively examined whether PTSD and depression are distinct constructs in an epidemiologic sample, as well as assessed the directionality of the PTSD-depression association across time. Methods 942 Detroit residents (males: n = 387; females: n = 555) were interviewed by phone at three time points, one year apart. At each time point, they were assessed for PTSD (using the PCL-C), depression (PHQ-9), trauma exposure, and stressful life events. Results First, a confirmatory factor analysis showed PTSD and depression to be two distinct factors at all 3 waves of assessments (W1, W2, and W3). Second, chi-square analysis detected significant differences between observed and expected rates of comorbidity at each time point, with significantly more no-disorder and comorbid cases, and significantly fewer PTSD only and depression only cases, than would be expected by chance alone. Finally, a cross-lagged analysis revealed a bidirectional association between PTSD and depression symptoms across time for the entire sample, as well as for women separately, wherein PTSD symptoms at an early wave predicted later depression symptoms, and vice versa. For men, however, only the paths from PTSD symptoms to subsequent depression symptoms were significant. Conclusions Across time, PTSD and depression are distinct, but correlated, constructs among a highly-exposed epidemiologic sample. Women and men differ in both the risk of these conditions, and the nature of the long-term associations between them. PMID:25044027

  14. Cocaine Withdrawal Impairs mGluR5-Dependent Long-Term Depression in Nucleus Accumbens Shell Neurons of Both Direct and Indirect Pathways.

    PubMed

    Huang, Chiung-Chun; Liang, Ying-Ching; Lee, Cheng-Che; Hsu, Kuei-Sen

    2015-12-01

    We previously reported that animals withdrawn from repeated cocaine exposure exhibited a selective deficit in the ability to elicit metabotropic glutamate receptor 5 (mGluR5)-dependent long-term depression (LTD) in the nucleus accumbens (NAc) shell. To determine whether such impairment occurs in the NAc in a cell-type-specific manner, we used bacterial artificial chromosome (BAC) transgenic mice expressing enhanced green fluorescent protein (eGFP) under the control of gene regulatory elements for the dopamine D1 receptor (Drd1) or dopamine D2 receptor (Drd2) to identify distinct subpopulations of medium spiny neurons (MSNs). We found that bath application of group I mGluR agonist (S)-3,5-dihydroxyphenylglycine (DHPG) reliably induced LTD in both NAc shell and core MSNs of wild-type, hemizygous Drd1-eGFP, and Drd2-eGFP mice. Confirming our previous results, cocaine withdrawal selectively impaired DHPG-LTD in NAc shell Drd1-expressing direct and Drd2-expressing indirect pathway MSNs. We also found that the expression of DHPG-LTD in NAc MSNs was not affected by the Ca(2+)-permeable α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor antagonist 1-naphthyl acetyl spermine. Furthermore, systemic administration of mGluR5-negative allosteric modulator fenobam before the daily injection of cocaine preserved mGluR5 function and significantly reduced the expression of cocaine-induced behavioral sensitization. These results reveal that withdrawal from repeated cocaine exposure may result in the impairment of NAc mGluR5-LTD in a subregion- but not cell-type-specific manner and suggests that pharmacological antagonism of mGluR5 may represent a potential strategy for reducing cocaine-induced addictive behaviors.

  15. Sustained Photosynthetic Performance of Coffea spp. under Long-Term Enhanced [CO2

    PubMed Central

    Ramalho, José C.; Rodrigues, Ana P.; Semedo, José N.; Pais, Isabel P.; Martins, Lima D.; Simões-Costa, Maria C.; Leitão, António E.; Fortunato, Ana S.; Batista-Santos, Paula; Palos, Isabel M.; Tomaz, Marcelo A.; Scotti-Campos, Paula; Lidon, Fernando C.; DaMatta, Fábio M.

    2013-01-01

    Coffee is one of the world’s most traded agricultural products. Modeling studies have predicted that climate change will have a strong impact on the suitability of current cultivation areas, but these studies have not anticipated possible mitigating effects of the elevated atmospheric [CO2] because no information exists for the coffee plant. Potted plants from two genotypes of Coffea arabica and one of C. canephora were grown under controlled conditions of irradiance (800 μmol m-2 s-1), RH (75%) and 380 or 700 μL CO2 L-1 for 1 year, without water, nutrient or root development restrictions. In all genotypes, the high [CO2] treatment promoted opposite trends for stomatal density and size, which decreased and increased, respectively. Regardless of the genotype or the growth [CO2], the net rate of CO2 assimilation increased (34-49%) when measured at 700 than at 380 μL CO2 L-1. This result, together with the almost unchanged stomatal conductance, led to an instantaneous water use efficiency increase. The results also showed a reinforcement of photosynthetic (and respiratory) components, namely thylakoid electron transport and the activities of RuBisCo, ribulose 5-phosphate kinase, malate dehydrogenase and pyruvate kinase, what may have contributed to the enhancements in the maximum rates of electron transport, carboxylation and photosynthetic capacity under elevated [CO2], although these responses were genotype dependent. The photosystem II efficiency, energy driven to photochemical events, non-structural carbohydrates, photosynthetic pigment and membrane permeability did not respond to [CO2] supply. Some alterations in total fatty acid content and the unsaturation level of the chloroplast membranes were noted but, apparently, did not affect photosynthetic functioning. Despite some differences among the genotypes, no clear species-dependent responses to elevated [CO2] were observed. Overall, as no apparent sign of photosynthetic down-regulation was found, our data

  16. Long-term postpartum anxiety and depression-like behavior in mother rats subjected to maternal separation are ameliorated by palatable high fat diet.

    PubMed

    Maniam, Jayanthi; Morris, Margaret J

    2010-03-17

    While the effects of maternal separation on pups are well studied, the impact on dams has attracted little attention. The consumption of palatable food is known to dampen stress responses in animals, and emotions influence food choice in humans. Here we examined the early- and long-term impacts of maternal separation on behavioral profile of the dams, and the effects of palatable cafeteria high-fat diet (HFD). After littering, Sprague-Dawley female rats were subjected to prolonged separation, S180 (180 min) or brief separation, S15 (15 min/day) from postnatal days (PND) 2-14. At 4 weeks postpartum, half the dams were assigned to HFD. Anxiety and depression-like behaviors were assessed pre- and post-diet. Compared to S15 dams, S180 dams consuming chow demonstrated increased anxiety and depression-like behaviors assessed by elevated plus maze (EPM) and forced swim (FST) tests, respectively. These behavioral deficits were observed at 4 weeks, and persisted until 17 weeks postpartum. The S180 dams also had increased plasma corticosterone concentration compared to S15 dams, which coincided with increased hypothalamic CRH mRNA and reduced hippocampal GR mRNA expression, suggesting possible dysregulation of hypothalamic-pituitary-adrenal axis activity. Interestingly, continuous provision of HFD improved the behavioral deficits observed in S180 dams with significant reduction of hypothalamic CRH mRNA expression. These data are the first to describe long-term detrimental behavioral impacts of separation in dams, suggesting this may provide a model of postpartum depression. Moreover, they support the notion of long-term beneficial effects of 'comfort food' on stress responses.

  17. The long-term effect of nitrite on the granule-based enhanced biological phosphorus removal system and the reversibility.

    PubMed

    Zheng, Xiongliu; Sun, Peide; Lou, Juqing; Fang, Zhiguo; Guo, Maoxin; Song, Yingqi; Tang, Xiudi; Jiang, Tao

    2013-03-01

    This study investigated the long-term effect of nitrite on the granule-based enhanced biological phosphorus removal (EBPR) system and the reversibility from macro- to micro-scale. Nitrite was found to seriously deteriorate the EBPR performance and result in severe sludge bulking. The inhibited polysaccharides excretion could lead to breaking the stability and integrity of the granules. Therefore, the reduced particle size and granule disintegration were observed. In this study, granules with lower ratio of proteins to polysaccharides (1.76) had better structure and function than the higher (3.84). Experimental results demonstrated that the microbial community structure was largely changed due to the presence of nitrite. In comparison, glycogen accumulating organisms (GAOs) had stronger resistibility and higher recovery rate than poly-phosphate accumulating organisms (PAOs). Interestingly, the community composition was unable to recover (Dice coefficients, 33.0%), although good EBPR performance was achieved only by propagating other types of PAOs.

  18. Startup and long term operation of enhanced biological phosphorus removal in continuous-flow reactor with granules.

    PubMed

    Li, Dong; Lv, Yufeng; Zeng, Huiping; Zhang, Jie

    2016-07-01

    The startup and long term operation of enhanced biological phosphorus removal (EBPR) in a continuous-flow reactor (CFR) with granules were investigated in this study. Through reducing the settling time from 9min to 3min gradually, the startup of EBPR in a CFR with granules was successfully realized in 16days. Under continuous-flow operation, the granules with good phosphorus and COD removal performance were stably operated for more than 6months. And the granules were characterized with particle size of around 960μm, loose structure and good settling ability. During the startup phase, polysaccharides (PS) was secreted excessively by microorganisms to resist the influence from the variation of operational mode. Results of relative quantitative PCR indicated that granules dominated by polyphosphate-accumulating organisms (PAOs) were easier accumulated in the CFR because more excellent settling ability was needed in the system.

  19. Symptoms of depression and anxiety predict treatment response and long-term physical health outcomes in rheumatoid arthritis: secondary analysis of a randomized controlled trial

    PubMed Central

    Norton, Sam; Scott, David L.; Steer, Sophia; Hotopf, Matthew

    2016-01-01

    Objective. The aim of this analysis is to examine the longitudinal impact of symptoms of depression/anxiety on treatment response, long-term disease activity and physical disability in RA. Methods. Secondary analysis of clinical trial data was performed. Data were collected at baseline and at 6-monthly intervals for 2 years. The EuroQoL (EQ-5DTM) indicated depression/anxiety symptom severity. Our primary outcomes of interest were (i) DAS-28 and (ii) physical disability measured via the HAQ. Secondary outcomes were: tender and swollen joint counts, patient global assessment, ESR and odds of reaching clinical remission. Multilevel models were used to assess the impact of baseline and persistent depression/anxiety on outcomes over 2 years. Results. Data from 379 patients were included. After adjusting for covariates, baseline depression/anxiety symptoms were associated with increased DAS-28 outcomes and increased tender joint counts. Persistent depression/anxiety symptoms were associated with increased DAS-28 scores, HAQ scores, tender joint counts and patient global assessment of disease activity, and reduced odds of reaching clinical remission. Patients with symptoms of depression/anxiety at baseline also showed a 50% reduction in prednisolone treatment effect, in comparison with patients with no symptoms of depression/anxiety at baseline. Conclusion. Baseline and persistent symptoms of depression/anxiety are associated with poorer health outcomes over time, as well as reduced treatment response. Mental health should be routinely measured both in clinical practice and in research, and managed alongside rheumatological disease to optimize health outcomes. Further research is required to examine whether treatment of mental disorders can improve rheumatological outcomes. PMID:26350486

  20. Delayed emergence of effects of memory-enhancing drugs: implications for the dynamics of long-term memory.

    PubMed Central

    Mondadori, C; Hengerer, B; Ducret, T; Borkowski, J

    1994-01-01

    Many theories of memory postulate that processing of information outlasts the learning situation and involves several different physiological substrates. If such physiologically distinct mechanisms or stages of memory do in fact exist, they should be differentially affected by particular experimental manipulations. Accordingly, a selective improvement of the processes underlying short-term memory should be detectable only while the information is encoded in the short-term mode, and a selective influence on long-term memory should be detectable only from the moment when memory is based on the long-term trace. Our comparative study of the time course of the effects of the cholinergic agonist arecoline, the gamma-aminobutyric acid type B receptor antagonist CGP 36742, the angiotensin-converting enzyme inhibitor captopril, and the nootropic oxiracetam, four substances with completely different primary sites of action, show that the memory-enhancing effects consistently come into evidence no sooner than 16-24 h after the learning trial. On the one hand, this finding suggests that all these substances act by way of the same type of mechanism; on the other hand, it demonstrates that the substrate modulated by the compounds forms the basis of memory only after 16-24 h. From the observation that animals also show clear signs of retention during the first 16 h--i.e., before the effects of the substances are measurable--it can be inferred that retention during this time is mediated by other mechanisms that are not influenced by any of the substances. Images PMID:8134347

  1. A Paradigm for Single-Case Research: The Time Series Study of a Long-Term Psychotherapy for Depression.

    ERIC Educational Resources Information Center

    Jones, Enrico E.; And Others

    1993-01-01

    Study articulates model for single-case research in psychotherapy. Saw patient with major depressive disorder for 2.5 years of psychotherapy. Videotaped sessions and obtained assessments of change at regular intervals. Used time-series analysis to model fluctuations in therapy process. Bidirectional analysis of causal effects showed that influence…

  2. 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.

  3. 5-HT4-Receptors Modulate Induction of Long-Term Depression but Not Potentiation at Hippocampal Output Synapses in Acute Rat Brain Slices

    PubMed Central

    Wawra, Matthias; Fidzinski, Pawel; Heinemann, Uwe; Mody, Istvan; Behr, Joachim

    2014-01-01

    The subiculum is the principal target of CA1 pyramidal cells and mediates hippocampal output to various cortical and subcortical regions of the brain. The majority of subicular pyramidal cells are burst-spiking neurons. Previous studies indicated that high frequency stimulation in subicular burst-spiking cells causes presynaptic NMDA-receptor dependent long-term potentiation (LTP) whereas low frequency stimulation induces postsynaptic NMDA-receptor-dependent long-term depression (LTD). In the present study, we investigate the effect of 5-hydroxytryptamine type 4 (5-HT4) receptor activation and blockade on both forms of synaptic plasticity in burst-spiking cells. We demonstrate that neither activation nor block of 5-HT4 receptors modulate the induction or expression of LTP. In contrast, activation of 5-HT4 receptors facilitates expression of LTD, and block of the 5-HT4 receptor prevents induction of short-term depression and LTD. As 5-HT4 receptors are positively coupled to adenylate cyclase 1 (AC1), 5-HT4 receptors might modulate PKA activity through AC1. Since LTD is blocked in the presence of 5-HT4 receptor antagonists, our data are consistent with 5-HT4 receptor activation by ambient serotonin or intrinsically active 5-HT4 receptors. Our findings provide new insight into aminergic modulation of hippocampal output. PMID:24505387

  4. Enhanced perisomatic inhibition and impaired long-term potentiation in the CA1 region of juvenile CHL1-deficient mice.

    PubMed

    Nikonenko, Alexander G; Sun, Mu; Lepsveridze, Eka; Apostolova, Ivayla; Petrova, Iveta; Irintchev, Andrey; Dityatev, Alexander; Schachner, Melitta

    2006-04-01

    The cell adhesion molecule, CHL1, like its close homologue L1, is important for normal brain development and function. In this study, we analysed the functional role of CHL1 in synaptic transmission in the CA1 region of the hippocampus using juvenile CHL1-deficient (CHL1-/-) and wild-type (CHL1+/+) mice. Inhibitory postsynaptic currents evoked in pyramidal cells by minimal stimulation of perisomatically projecting interneurons were increased in CHL1-/- mice compared with wild-type littermates. Also, long-term potentiation (LTP) at CA3-CA1 excitatory synapses was reduced under physiological conditions in CHL1-/- mice. This abnormality was abolished by application of a GABAA receptor antagonist, suggesting that enhanced inhibition is the cause of LTP impairment. Quantitative ultrastructural and immunohistochemical analyses revealed aberrations possibly related to the abnormally high inhibition observed in CHL1-/- mice. The length and linear density of active zones in symmetric synapses on pyramidal cell bodies, as well as number of perisomatic puncta containing inhibitory axonal markers were increased. Density and total number of parvalbumin-positive interneurons was also abnormally high. These observations and the finding that CA1 interneurons express CHL1 protein indicate that CHL1 is important for regulation of inhibitory synaptic transmission and interneuron populations in the postnatal brain. The observed enhancement of inhibitory transmission in CHL1-/- mice is in contrast to the previous finding of reduced inhibition in L1 deficient mice and indicates different functions of these two closely related molecules.

  5. Long-term study on the impact of temperature on enhanced biological phosphorus and nitrogen removal in membrane bioreactor.

    PubMed

    Sayi-Ucar, N; Sarioglu, M; Insel, G; Cokgor, E U; Orhon, D; van Loosdrecht, M C M

    2015-11-01

    The study involved experimental observation and performance evaluation of a membrane bioreactor system treating municipal wastewater for nutrient removal for a period 500 days, emphasizing the impact of high temperature on enhanced biological phosphorus removal (EBPR). The MBR system was operated at relatively high temperatures (24-41 °C). During the operational period, the total phosphorus (TP) removal gradually increased from 50% up to 95% while the temperature descended from 41 to 24 °C. At high temperatures, anaerobic volatile fatty acid (VFA) uptake occurred with low phosphorus release implying the competition of glycogen accumulating organisms (GAOs) with polyphosphate accumulating organisms (PAOs). Low dissolved oxygen conditions associated with high wastewater temperatures did not appreciable affected nitrification but enhanced nitrogen removal. Dissolved oxygen levels around 1.0 mgO2/L in membrane tank provided additional denitrification capacity of 6-7 mgN/L by activating simultaneous nitrification and denitrification. As a result, nearly complete removal of nitrogen could be achieved in the MBR system, generating a permeate with no appreciable nitrogen content. The gross membrane flux was 43 LMH corresponding to the specific permeability (K) of 413 LMH/bar at 39 °C in the MBR tank. The specific permeability increased by the factor of 43% at 39 °C compared to that of 25 °C during long-term operation.

  6. Stress enhances fear by forming new synapses with greater capacity for long-term potentiation in the amygdala

    PubMed Central

    Suvrathan, Aparna; Bennur, Sharath; Ghosh, Supriya; Tomar, Anupratap; Anilkumar, Shobha; Chattarji, Sumantra

    2014-01-01

    Prolonged and severe stress leads to cognitive deficits, but facilitates emotional behaviour. Little is known about the synaptic basis for this contrast. Here, we report that in rats subjected to chronic immobilization stress, long-term potentiation (LTP) and NMDA receptor (NMDAR)-mediated synaptic responses are enhanced in principal neurons of the lateral amygdala, a brain area involved in fear memory formation. This is accompanied by electrophysiological and morphological changes consistent with the formation of ‘silent synapses’, containing only NMDARs. In parallel, chronic stress also reduces synaptic inhibition. Together, these synaptic changes would enable amygdalar neurons to undergo further experience-dependent modifications, leading to stronger fear memories. Consistent with this prediction, stressed animals exhibit enhanced conditioned fear. Hence, stress may leave its mark in the amygdala by generating new synapses with greater capacity for plasticity, thereby creating an ideal neuronal substrate for affective disorders. These findings also highlight the unique features of stress-induced plasticity in the amygdala that are strikingly different from the stress-induced impairment of structure and function in the hippocampus. PMID:24298153

  7. 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 ...

  8. Hippocampal NR2B-containing NMDA receptors enhance long-term potentiation in rats with chronic visceral pain.

    PubMed

    Chen, Yu; Chen, Ai-qin; Luo, Xiao-qing; Guo, Li-xia; Tang, Ying; Bao, Cheng-jia; Lin, Ling; Lin, Chun

    2014-06-27

    Pain and learning memory have striking similarities in synaptic plasticity. Activation of the N-methyl-D-aspartic acid receptors 2B subunits (NR2B-NMDAs) is responsible for the hippocampal LTP in memory formation. In our previous studies, we found the significant enhancement of CA1 hippocampal long-term potentiation (LTP) induced by high-frequency stimulation (HFS) in rats with chronic visceral pain. However, it is unclear whether the NR2B-NMDAs are required for the LTP in chronic visceral pain. In this study, a rat model with irritable bowel syndrome (IBS) was established by colorectal distention (CRD). The sensitivity of visceral pain and HFS-induced LTP at SC-CA1 synapses were significantly enhanced in IBS-like rats (p<0.05). In addition, hippocampal NR2B protein levels significantly increased in IBS-like rats (p<0.05). To test whether NR2B-NMDAs are responsible for the LTP, effects of Ro 25-6981, a selective antagonist of NR2B-NMDAs, on field potential in CA1 region were investigated in vitro. Our results demonstrated that Ro 25-6981 dose-dependently inhibited the facilitation of CA1 LTP in IBS-like rats. The plausible activation mechanism of hippocampal NR2B-NMDAs in the LTP enhancement was further explored. Western blot data indicated that expression of tyrosine phosphorylated NR2B protein in hippocampus significantly enhanced in IBS-like rats. Accordingly, genistein, a specific inhibitor of tyrosine kinases, dose-dependently blocked the facilitation of hippocampal LTP in IBS-like rats. Furthermore, EMG data revealed that intra-hippocampal injection of Ro 25-6981 dose-dependently attenuated the visceral hypersensitivity. In conclusion, hippocampal NR2B-NMDAs are responsible for the facilitation of CA1 LTP via tyrosine phosphorylation, which leads to visceral hypersensitivity.

  9. Long-term course of severe depression: late remission and recurrence may be found in a follow-up after 38–53 years

    PubMed Central

    Crona, Lisa; Brådvik, Louise

    2012-01-01

    This study is a follow-up of inpatients diagnosed with severe depression/melancholia between 1956 and 1969. During this period, all inpatients at the Department of Psychiatry, University Hospital, Lund, were rated on a multidimensional diagnostic schedule on discharge. There were 471 patients born from 1920 onward. In the present follow-up, 2006 to 2010, 169 survivors could be traced. They were asked to participate in the study involving a telephone interview, in which a structured life chart was used. Of the patients contacted, 16 were ill or confused and 3 did not remember ever being depressed, leaving 150 who could participate. Seventy-five of these agreed to participate in the study. Long-term course of depression was evaluated by cluster analysis and compared to background variables, such as heredity for depression, perceived parental rearing behaviour, and treatment of index depressive episode. Using a cluster analysis the patients could be separated into six clusters describing the course: i) single or few episodes followed by long-lasting remission; ii) single or few episodes followed by long-lasting remission, although shorter; iii) single or few episodes followed by late recurrence; iv) single or few episodes, but more frequently ill, followed by late recurrence; v) several episodes followed by lasting remission; vi) chronic course of episodes. Remission or recurrence could therefore occur even after more than a decade. In summary, there was a short-term course with or without recurrence or a chronic course with or without late remission. Heredity for depression was significantly related to a chronic course with or without late remission. PMID:25478118

  10. Evidence for a fragile X mental retardation protein-mediated translational switch in metabotropic glutamate receptor-triggered Arc translation and long-term depression.

    PubMed

    Niere, Farr; Wilkerson, Julia R; Huber, Kimberly M

    2012-04-25

    Group 1 metabotropic glutamate receptor (mGluR)-stimulated protein synthesis and long-term synaptic depression (mGluR-LTD) are altered in the mouse model of fragile X syndrome, Fmr1 knock-out (KO) mice. Fmr1 encodes fragile X mental retardation protein (FMRP), a dendritic RNA binding protein that functions, in part, as a translational suppressor. It is unknown whether and how FMRP acutely regulates LTD and/or the rapid synthesis of new proteins required for LTD, such as the activity-regulated cytoskeletal-associated protein (Arc). The protein phosphatase PP2A dephosphorylates FMRP, which contributes to translational activation of some target mRNAs. Here, we report that PP2A and dephosphorylation of FMRP at S500 are required for an mGluR-induced, rapid (5 min) increase in dendritic Arc protein and LTD in rat and mouse hippocampal neurons. In Fmr1 KO neurons, basal, dendritic Arc protein levels and mGluR-LTD are enhanced, but mGluR-triggered Arc synthesis is absent. Lentiviral-mediated expression of wild-type FMRP in Fmr1 KO neurons suppresses basal dendritic Arc levels and mGluR-LTD, and restores rapid mGluR-triggered Arc synthesis. A phosphomimic of FMRP (S500D) suppresses steady-state dendritic Arc levels but does not rescue mGluR-induced Arc synthesis. A dephosphomimic of FMRP (S500A) neither suppresses dendritic Arc nor supports mGluR-induced Arc synthesis. Accordingly, S500D-FMRP expression in Fmr1 KO neurons suppresses mGluR-LTD, whereas S500A-FMRP has no effect. These data support a model in which phosphorylated FMRP functions to suppress steady-state translation of Arc and LTD. Upon mGluR activation of PP2A, FMRP is rapidly dephosphorylated, which contributes to rapid new synthesis of Arc and mGluR-LTD.

  11. Global deep ocean oxygenation by enhanced ventilation in the Southern Ocean under long-term global warming

    NASA Astrophysics Data System (ADS)

    Yamamoto, A.; Abe-Ouchi, A.; Shigemitsu, M.; Oka, A.; Takahashi, K.; Ohgaito, R.; Yamanaka, Y.

    2015-10-01

    Global warming is expected to decrease ocean oxygen concentrations by less solubility of surface ocean and change in ocean circulation. The associated expansion of the oxygen minimum zone would have adverse impacts on marine organisms and ocean biogeochemical cycles. Oxygen reduction is expected to persist for a thousand years or more, even after atmospheric carbon dioxide stops rising. However, long-term changes in ocean oxygen and circulation are still unclear. Here we simulate multimillennium changes in ocean circulation and oxygen under doubling and quadrupling of atmospheric carbon dioxide, using a fully coupled atmosphere-ocean general circulation model and an offline biogeochemical model. In the first 500 years, global oxygen concentration decreases, consistent with previous studies. Thereafter, however, the oxygen concentration in the deep ocean globally recovers and overshoots at the end of the simulations, despite surface oxygen decrease and weaker Atlantic meridional overturning circulation. This is because, after the initial cessation, the recovery and overshooting of deep ocean convection in the Weddell Sea enhance ventilation and supply oxygen-rich surface waters to deep ocean. Another contributor to deep ocean oxygenation is seawater warming, which reduces the export production and shifts the organic matter remineralization to the upper water column. Our results indicate that the change in ocean circulation in the Southern Ocean potentially drives millennial-scale oxygenation in deep ocean, which is opposite to the centennial-scale global oxygen reduction and general expectation.

  12. Compound stimulus presentation and the norepinephrine reuptake inhibitor atomoxetine enhance long-term extinction of cocaine-seeking behavior.

    PubMed

    Janak, Patricia H; Bowers, M Scott; Corbit, Laura H

    2012-03-01

    Drug abstinence is frequently compromised when addicted individuals are re-exposed to environmental stimuli previously associated with drug use. Research with human addicts and in animal models has demonstrated that extinction learning (non-reinforced cue-exposure) can reduce the capacity of such stimuli to induce relapse, yet extinction therapies have limited long-term success under real-world conditions (Bouton, 2002; O'Brien, 2008). We hypothesized that enhancing extinction would reduce the later ability of drug-predictive cues to precipitate drug-seeking behavior. We, therefore, tested whether compound stimulus presentation and pharmacological treatments that augment noradrenergic activity (atomoxetine; norepinephrine reuptake inhibitor) during extinction training would facilitate the extinction of drug-seeking behaviors, thus reducing relapse. Rats were trained that the presentation of a discrete cue signaled that a lever press response would result in cocaine reinforcement. Rats were subsequently extinguished and spontaneous recovery of drug-seeking behavior following presentation of previously drug-predictive cues was tested 4 weeks later. We find that compound stimulus presentations or pharmacologically increasing noradrenergic activity during extinction training results in less future recovery of responding, whereas propranolol treatment reduced the benefit seen with compound stimulus presentation. These data may have important implications for understanding the biological basis of extinction learning, as well as for improving the outcome of extinction-based therapies.

  13. Long-term moderate elevation of corticosterone facilitates avian food-caching behaviour and enhances spatial memory.

    PubMed Central

    Pravosudov, Vladimir V

    2003-01-01

    It is widely assumed that chronic stress and corresponding chronic elevations of glucocorticoid levels have deleterious effects on animals' brain functions such as learning and memory. Some animals, however, appear to maintain moderately elevated levels of glucocorticoids over long periods of time under natural energetically demanding conditions, and it is not clear whether such chronic but moderate elevations may be adaptive. I implanted wild-caught food-caching mountain chickadees (Poecile gambeli), which rely at least in part on spatial memory to find their caches, with 90-day continuous time-release corticosterone pellets designed to approximately double the baseline corticosterone levels. Corticosterone-implanted birds cached and consumed significantly more food and showed more efficient cache recovery and superior spatial memory performance compared with placebo-implanted birds. Thus, contrary to prevailing assumptions, long-term moderate elevations of corticosterone appear to enhance spatial memory in food-caching mountain chickadees. These results suggest that moderate chronic elevation of corticosterone may serve as an adaptation to unpredictable environments by facilitating feeding and food-caching behaviour and by improving cache-retrieval efficiency in food-caching birds. PMID:14728783

  14. Nampt is required for long-term depression and the function of GluN2B subunit-containing NMDA receptors

    PubMed Central

    Stein, Liana Roberts; Zorumski, Charles F.; Imai, Shin-ichiro; Izumi, Yukitoshi

    2015-01-01

    Nicotinamide adenine dinucleotide (NAD+) is an essential coenzyme/cosubstrate for many biological processes in cellular metabolism. The rate-limiting step in the major pathway of mammalian NAD+ biosynthesis is mediated by nicotinamide phosphoribosyltransferase (Nampt). Previously, we showed that mice lacking Nampt in forebrain excitatory neurons (CamKIIαNampt−/− mice) exhibited hyperactivity, impaired learning and memory, and reduced anxiety-like behaviors. However, it remained unclear if these functional effects were accompanied by synaptic changes. Here, we show that CamKIIαNampt−/− mice have impaired induction of long-term depression (LTD) in the Schaffer collateral pathway, but normal induction of long-term potentiation (LTP), at postnatal day 30. Pharmacological assessments demonstrated that CamKIIαNampt−/− mice also display dysfunction of synaptic GluN2B (NR2B)-containing N-methyl-D-aspartate receptors (NMDARs) prior to changes in NMDAR subunit expression. These results support a novel, important role for Nampt-mediated NAD+ biosynthesis in LTD and in the function of GluN2B–containing NMDARs. PMID:26481044

  15. Protease Activated Receptor 2 (PAR2) Induces Long-Term Depression in the Hippocampus through Transient Receptor Potential Vanilloid 4 (TRPV4)

    PubMed Central

    Shavit-Stein, Efrat; Artan-Furman, Avital; Feingold, Ekaterina; Ben Shimon, Marina; Itzekson-Hayosh, Zeev; Chapman, Joab; Vlachos, Andreas; Maggio, Nicola

    2017-01-01

    Protease activated receptors (PARs) are involved in regulating synaptic transmission and plasticity in the brain. While it is well-accepted that PAR1 mediates long-term potentiation (LTP) of excitatory synaptic strength, the role of PAR2 in synaptic plasticity remains not well-understood. In this study, we assessed the role of PAR2-signaling in plasticity at hippocampal Schaffer collateral-CA1 synapses. Using field potential recordings, we report that PAR2-activation leads to long-term depression (LTD) of synaptic transmission through a protein kinase A -dependent, Transient Receptor Potential Vanilloid 4 -mediated mechanism, which requires the activation of N-methyl-D-aspartate receptors. These results demonstrate that the effects of PAR2 on synaptic plasticity are distinct from what is observed upon PAR1-activation. Thus, we propose that the activation of different classes of PARs, i.e., PAR1 and PAR2, may set the threshold of synaptic plasticity in the hippocampal network by balancing LTP and LTD. PMID:28303089

  16. 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

  17. The eIF2α kinase PERK limits the expression of hippocampal metabotropic glutamate receptor-dependent long-term depression.

    PubMed

    Trinh, Mimi A; Ma, Tao; Kaphzan, Hanoch; Bhattacharya, Aditi; Antion, Marcia D; Cavener, Douglas R; Hoeffer, Charles A; Klann, Eric

    2014-04-16

    The proper regulation of translation is required for the expression of long-lasting synaptic plasticity. A major site of translational control involves the phosphorylation of eukaryotic initiation factor 2 α (eIF2α) by PKR-like endoplasmic reticulum (ER) kinase (PERK). To determine the role of PERK in hippocampal synaptic plasticity, we used the Cre-lox expression system to selectively disrupt PERK expression in the adult mouse forebrain. Here, we demonstrate that in hippocampal area CA1, metabotropic glutamate receptor (mGluR)-dependent long-term depression (LTD) is associated with increased eIF2α phosphorylation, whereas stimulation of early- and late-phase long-term potentiation (E-LTP and L-LTP, respectively) is associated with decreased eIF2α phosphorylation. Interesting, although PERK-deficient mice exhibit exaggerated mGluR-LTD, both E-LTP and L-LTP remained intact. We also found that mGluR-LTD is associated with a PERK-dependent increase in eIF2α phosphorylation. Our findings are consistent with the notion that eIF2α phosphorylation is a key site for the bidirectional control of persistent forms of synaptic LTP and LTD and suggest a distinct role for PERK in mGluR-LTD.

  18. Long-term enhancement of synaptic transmission between antennal lobe and mushroom body in cultured Drosophila brain.

    PubMed

    Ueno, Kohei; Naganos, Shintaro; Hirano, Yukinori; Horiuchi, Junjiro; Saitoe, Minoru

    2013-01-01

    In Drosophila, the mushroom body (MB) is a critical brain structure for olfactory associative learning. During aversive conditioning, the MBs are thought to associate odour signals, conveyed by projection neurons (PNs) from the antennal lobe (AL), with shock signals conveyed through ascending fibres of the ventral nerve cord (AFV). Although synaptic transmission between AL and MB might play a crucial role for olfactory associative learning, its physiological properties have not been examined directly. Using a cultured Drosophila brain expressing a Ca(2+) indicator in the MBs, we investigated synaptic transmission and plasticity at the AL-MB synapse. Following stimulation with a glass micro-electrode, AL-induced Ca(2+) responses in the MBs were mediated through Drosophila nicotinic acetylcholine receptors (dnAChRs), while AFV-induced Ca(2+) responses were mediated through Drosophila NMDA receptors (dNRs). AL-MB synaptic transmission was enhanced more than 2 h after the simultaneous 'associative-stimulation' of AL and AFV, and such long-term enhancement (LTE) was specifically formed at the AL-MB synapses but not at the AFV-MB synapses. AL-MB LTE was not induced by intense stimulation of the AL alone, and the LTE decays within 60 min after subsequent repetitive AL stimulation. These phenotypes of associativity, input specificity and persistence of AL-MB LTE are highly reminiscent of olfactory memory. Furthermore, similar to olfactory aversive memory, AL-MB LTE formation required activation of the Drosophila D1 dopamine receptor, DopR, along with dnAChR and dNR during associative stimulations. These physiological and genetic analogies indicate that AL-MB LTE might be a relevant cellular model for olfactory memory.

  19. Serotonin receptor subtypes required for ventilatory long-term facilitation and its enhancement after chronic intermittent hypoxia in awake rats.

    PubMed

    McGuire, Michelle; Zhang, Yi; White, David P; Ling, Liming

    2004-02-01

    Respiratory long-term facilitation (LTF), a serotonin-dependent, persistent augmentation of respiratory activity after episodic hypoxia, is enhanced by pretreatment of chronic intermittent hypoxia (CIH; 5 min 11-12% O2-5 min air, 12 h/night for 7 nights). The present study examined the effects of methysergide (serotonin 5-HT1,2,5,6,7 receptor antagonist), ketanserin (5-HT2 antagonist), or clozapine (5-HT2,6,7 antagonist) on both ventilatory LTF and the CIH effect on ventilatory LTF in conscious male adult rats to determine which specific receptor subtype(s) is involved. In untreated rats (i.e., animals not exposed to CIH), LTF, induced by five episodes of 5-min poikilocapnic hypoxia (10% O2) separated by 5-min normoxic intervals, was measured twice by plethysmography. Thus the measurement was conducted 1-2 days before (as control) and approximately 1 h after systemic injection of methysergide (1 mg/kg ip), ketanserin (1 mg/kg), or clozapine (1.5 mg/kg). Resting ventilation, metabolic rate, and hypoxic ventilatory response (HVR) were unchanged, but LTF ( approximately 18% above baseline) was eliminated by each drug. In CIH-treated rats, LTF was also measured twice, before and approximately 8 h after CIH. Vehicle, methysergide, ketanserin, or clozapine was injected approximately 1 h before the second measurement. Neither resting ventilation nor metabolic rate was changed after CIH and/or any drug. HVR was unchanged after methysergide and ketanserin but reduced in four of seven clozapine rats. The CIH-enhanced LTF ( approximately 28%) was abolished by methysergide and clozapine but only attenuated by ketanserin (to approximately 10%). Collectively, these data suggest that ventilatory LTF requires 5-HT2 receptors and that the CIH effect on LTF requires non-5-HT2 serotonin receptors, probably 5-HT6 and/or 5-HT7 subtype(s).

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

    PubMed Central

    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 Ca2+ 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. PMID:26236206

  1. Long-term enhancement of synaptic transmission between antennal lobe and mushroom body in cultured Drosophila brain

    PubMed Central

    Ueno, Kohei; Naganos, Shintaro; Hirano, Yukinori; Horiuchi, Junjiro; Saitoe, Minoru

    2013-01-01

    In Drosophila, the mushroom body (MB) is a critical brain structure for olfactory associative learning. During aversive conditioning, the MBs are thought to associate odour signals, conveyed by projection neurons (PNs) from the antennal lobe (AL), with shock signals conveyed through ascending fibres of the ventral nerve cord (AFV). Although synaptic transmission between AL and MB might play a crucial role for olfactory associative learning, its physiological properties have not been examined directly. Using a cultured Drosophila brain expressing a Ca2+ indicator in the MBs, we investigated synaptic transmission and plasticity at the AL–MB synapse. Following stimulation with a glass micro-electrode, AL-induced Ca2+ responses in the MBs were mediated through Drosophila nicotinic acetylcholine receptors (dnAChRs), while AFV-induced Ca2+ responses were mediated through Drosophila NMDA receptors (dNRs). AL–MB synaptic transmission was enhanced more than 2 h after the simultaneous ‘associative-stimulation’ of AL and AFV, and such long-term enhancement (LTE) was specifically formed at the AL–MB synapses but not at the AFV–MB synapses. AL–MB LTE was not induced by intense stimulation of the AL alone, and the LTE decays within 60 min after subsequent repetitive AL stimulation. These phenotypes of associativity, input specificity and persistence of AL–MB LTE are highly reminiscent of olfactory memory. Furthermore, similar to olfactory aversive memory, AL–MB LTE formation required activation of the Drosophila D1 dopamine receptor, DopR, along with dnAChR and dNR during associative stimulations. These physiological and genetic analogies indicate that AL–MB LTE might be a relevant cellular model for olfactory memory. PMID:23027817

  2. Regulation of fear extinction by long-term depression: The roles of endocannabinoids and brain derived neurotrophic factor.

    PubMed

    Bennett, Maxwell R; Arnold, Jonathon; Hatton, Sean N; Lagopoulos, Jim

    2017-02-15

    The extinction of a conditioned fear response is of great interest in the search for a means of ameliorating adverse neurobiological changes resulting from stress. The discovery that endocannibinoid (EC) levels are inversely related to the extent of such stress, and that the amygdala is a primary site mediating stress, suggests that ECs in this brain region might play a major role in extinction. Supporting this are the observations that the basolateral complex of the amygdala shows an increase in ECs only during extinction and that early clinical trials indicate that cannabinoid-like agents, when taken orally by patients suffering from post traumatic stress disorder (PTSD), reduce insomnia and nightmares. In order to optimize the potential of these agents to ameliorate symptoms of PTSD four important questions need to be answered: first, what is the identity of the cells that release ECs in the amygdala during extinction; second, what are their sites of action; third, what roles do the ECs play in the alleviation of long- depression (LTD), a process central to extinction; and finally, to what extent does brain derived neurotrophic factor (BDNF) facilitate the release of ECs? A review of the relevant literature is presented in an attempt to answer these questions. It is suggested that the principal cell involved in EC synthesis and release during extinction is the so-called excitatory extinction neuron in the basal nucleus of the amygdala. Furthermore that the main site of action of the ECs is the adjacent calcitonin gene-related peptide inhibitory interneurons, whose normal role of blocking the excitatory neurons is greatly diminished. The molecular pathways leading (during extinction trials) to the synthesis and release of ECs from synaptic spines of extinction neurons, that is potentiated by BDNF, are also delineated in this review. Finally, consideration is given to how the autocrine action of BDNF, linked to the release of ECs, can lead to the sustained release

  3. Enhancement of cancer stem-like and epithelial−mesenchymal transdifferentiation property in oral epithelial cells with long-term nicotine exposure: Reversal by targeting SNAIL

    SciTech Connect

    Yu, Cheng-Chia; Chang, Yu-Chao

    2013-02-01

    Cigarette smoking is one of the major risk factors in the development and further progression of tumorigenesis, including oral squamous cell carcinoma (OSCC). Recent studies suggest that interplay cancer stem-like cells (CSCs) and epithelial−mesenchymal transdifferentiation (EMT) properties are responsible for the tumor maintenance and metastasis in OSCC. The aim of the present study was to investigate the effects of long-term exposure with nicotine, a major component in cigarette, on CSCs and EMT characteristics. The possible reversal regulators were further explored in nicotine-induced CSCs and EMT properties in human oral epithelial (OE) cells. Long-term exposure with nicotine was demonstrated to up-regulate ALDH1 population in normal gingival and primary OSCC OE cells dose-dependently. Moreover, long-term nicotine treatment was found to enhance the self-renewal sphere-forming ability and stemness gene signatures expression and EMT regulators in OE cells. The migration/cell invasiveness/anchorage independent growth and in vivo tumor growth by nude mice xenotransplantation assay was enhanced in long-term nicotine-stimulated OE cells. Knockdown of Snail in long-term nicotine-treated OE cells was found to reduce their CSCs properties. Therapeutic delivery of Si-Snail significantly blocked the xenograft tumorigenesis of long-term nicotine-treated OSCC cells and largely significantly improved the recipient survival. The present study demonstrated that the enrichment of CSCs coupled EMT property in oral epithelial cells induced by nicotine is critical for the development of OSCC tumorigenesis. Targeting Snail might offer a new strategy for the treatment of OSCC patients with smoking habit. -- Highlights: ► Sustained nicotine treatment induced CSCs properties of oral epithelial cells. ► Long-term nicotine treatment enhance EMT properties of oral epithelial cells. ► Long-term nicotine exposure increased tumorigenicity of oral epithelial cells. ► Si

  4. Bidirectional regulation of synaptic transmission by BRAG1/IQSEC2 and its requirement in long-term depression

    PubMed Central

    Brown, Joshua C.; Petersen, Amber; Zhong, Ling; Himelright, Miranda L.; Murphy, Jessica A.; Walikonis, Randall S.; Gerges, Nashaat Z.

    2016-01-01

    Dysfunction of the proteins regulating synaptic function can cause synaptic plasticity imbalance that underlies neurological disorders such as intellectual disability. A study found that four distinct mutations within BRAG1, an Arf-GEF synaptic protein, each led to X-chromosome-linked intellectual disability (XLID). Although the physiological functions of BRAG1 are poorly understood, each of these mutations reduces BRAG1's Arf-GEF activity. Here we show that BRAG1 is required for the activity-dependent removal of AMPA receptors in rat hippocampal pyramidal neurons. Moreover, we show that BRAG1 bidirectionally regulates synaptic transmission. On one hand, BRAG1 is required for the maintenance of synaptic transmission. On the other hand, BRAG1 expression enhances synaptic transmission, independently of BRAG1 Arf-GEF activity or neuronal activity, but dependently on its C-terminus interactions. This study demonstrates a dual role of BRAG1 in synaptic function and highlights the functional relevance of reduced BRAG1 Arf-GEF activity as seen in the XLID-associated human mutations. PMID:27009485

  5. Long-term exposure to estrogen enhances chemotherapeutic efficacy potentially through epigenetic mechanism in human breast cancer cells

    PubMed Central

    Chang, Yu-Wei

    2017-01-01

    Chemotherapy is the most common clinical option for treatment of breast cancer. However, the efficacy of chemotherapy depends on the age of breast cancer patients. Breast tissues are estrogen responsive and the levels of ovarian estrogen vary among the breast cancer patients primarily between pre- and post-menopausal age. Whether this age-dependent variation in estrogen levels influences the chemotherapeutic efficacy in breast cancer patients is not known. Therefore, the objective of this study was to evaluate the effects of natural estrogen 17 beta-estradiol (E2) on the efficacy of chemotherapeutic drugs in breast cancer cells. Estrogen responsive MCF-7 and T47D breast cancer cells were long-term exposed to 100 pg/ml estrogen, and using these cells the efficacy of chemotherapeutic drugs doxorubicin and cisplatin were determined. The result of cell viability and cell cycle analysis revealed increased sensitivities of doxorubicin and cisplatin in estrogen-exposed MCF-7 and T47D cells as compared to their respective control cells. Gene expression analysis of cell cycle, anti-apoptosis, DNA repair, and drug transporter genes further confirmed the increased efficacy of chemotherapeutic drugs in estrogen-exposed cells at molecular level. To further understand the role of epigenetic mechanism in enhanced chemotherapeutic efficacy by estrogen, cells were pre-treated with epigenetic drugs, 5-aza-2-deoxycytidine and Trichostatin A prior to doxorubicin and cisplatin treatments. The 5-aza-2 deoxycytidine pre-treatment significantly decreased the estrogen-induced efficacy of doxorubicin and cisplatin, suggesting the role of estrogen-induced hypermethylation in enhanced sensitivity of these drugs in estrogen-exposed cells. In summary, the results of this study revealed that sensitivity to chemotherapy depends on the levels of estrogen in breast cancer cells. Findings of this study will have clinical implications in selecting the chemotherapy strategies for treatment of breast

  6. Contribution of voltage-gated Ca2+ channels to homosynaptic long-term depression in the CA1 region in vitro.

    PubMed

    Christie, B R; Schexnayder, L K; Johnston, D

    1997-03-01

    Homosynaptic long-term depression (LTD) of synaptic efficacy was induced in field excitatory postsynaptic potentials by administration of 900 pulses at either 1 or 3 Hz in 2- to 3-wk-old Sprague-Dawley rats. The stimulation was administered via a bipolar stimulating electrode placed immediately adjacent to the recording electrode in the stratum radiatum region of the hippocampal CA1 subfield. Equivalent LTD induction occurred whether the slices were maintained at room temperature or at 32 degrees C. Lowering bath Ca2+ to 0 mM, or increasing it to 4 mM, prevented the induction of the depression. The NMDA receptor antagonist D,L-2-amino-5-phosphonovaleric acid (50 microM) reversibly blocked the induction of homosynaptic LTD. In addition, the L-type voltage-gated calcium channel (VGCC) antagonist nimodipine (10 microM) and the R- and T-type VGCC antagonist NiCl2 (25 microM) also prevented homosynaptic LTD induction. These results indicate that in addition to N-methyl-D-aspartate receptor activity, Ca2+ influx via VGCCs can play an important role in the induction and expression of LTD induced by low-frequency stimulation in the hippocampal formation.

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

    PubMed Central

    Otani, Satoru; Connor, John A

    1998-01-01

    During block of γ-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). Ratio imaging with fura-2 revealed moderate dendritic [Ca2+] increases (≈500 nM) during only the initial ≈30 s of the 7.5 min stimulation period. Conditioning for 30 s was, however, insufficient to induce LTD. The [Ca2+] changes were insensitive to the metabotropic glutamate receptor (mGluR) antagonist (+)-α-methyl-4-carboxyphenylglycine (MCPG). MCPG, however, completely blocked LTD when present during conditioning. The [Ca2+] changes were abolished by postsynaptic hyperpolarization (-110 mV at the soma). Hyperpolarizing neurons to -110 mV during conditioning significantly attenuated LTD induction. LTD induction was also blocked by the postsynaptic presence of the protein kinase C inhibitor peptide PKC(19-36). 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. PMID:9714858

  8. Long-term depression and suicidal ideation outcomes subsequent to emancipation from foster care: pathways to psychiatric risk in the Métis population.

    PubMed

    Kaspar, Violet

    2014-02-28

    Major depressive episode (MDE) and suicidal ideation (SI) associated with history of foster care placement (HxFCP), and mediating effects of psychosocial and socioeconomic factors through which placement may confer psychiatric risks in the years subsequent to emancipation were examined in a national sample of 7534 Métis. More than one third of emancipated respondents reported past year MDE, a prevalence rate nearly 50% higher than the rate of MDE among Métis respondents without a history of placement in foster care. The 25% lifetime prevalence rate of SI in the emancipated group was more than twice the rate observed in the non-fostered group. Direct effects of HxFCP on post placement MDE and SI were significant in multivariate logistic regression analyses, even when effects of childhood predispositional risk factors were controlled statistically. Emancipated individuals were unduly affected by psychosocial and socioeconomic disadvantages signifying pathways that linked foster care placement history and psychiatric status. Main mediators of the effects demonstrated using effect decomposition procedures were self-esteem, income, and community adversity. The findings warrant consideration of foster care history in clarifying the complex etiologies of suicidal ideation and major depressive episode in the Métis population and risk factors ensuing in the intervening years as integral to the process linking placement to long-term psychiatric outcomes.

  9. Asynchronous Pre- and Postsynaptic Activity Induces Associative Long-Term Depression in Area CA1 of the Rat Hippocampus in vitro

    NASA Astrophysics Data System (ADS)

    Debanne, Dominique; Gahwiler, Beat H.; Thompson, Scott M.

    1994-02-01

    Associative long-term depression (LTD) was induced in hippocampal slice cultures with repeated low-frequency (0.3 Hz) stimulation of the Schaffer collateral pathway, only when such stimuli were preceded by intracellular injection of brief depolarizing current pulses in the postsynaptic CA1 pyramidal cell. The decrease in excitatory postsynaptic potential amplitude lasted >30 min, could be reversed by induction of potentiation, could be induced at previously potentiated inputs, was input-specific, and did not require activation or potentiation of other inputs. The magnitude of the depression depended upon the time interval between depolarization and stimulation and upon the duration of the depolarizing pulse. LTD was not observed in neurons impaled with electrodes containing a Ca2+ chelator. LTD could not be induced in the presence of an N-methyl-D-aspartate receptor antagonist, suggesting that voltage-dependent Ca2+ influx is necessary but not sufficient for LTD induction. We conclude that associative LTD results when synaptic activity follows postsynaptic depolarization within a circumscribed time window.

  10. Single fluoxetine treatment before but not after stress prevents stress-induced hippocampal long-term depression and spatial memory retrieval impairment in rats.

    PubMed

    Han, Huili; Dai, Chunfang; Dong, Zhifang

    2015-07-28

    A growing body of evidence has shown that chronic treatment with fluoxetine, a widely prescribed medication for treatment of depression, can affect synaptic plasticity in the adult central nervous system. However, it is not well understood whether acute fluoxetine influences synaptic plasticity, especially on hippocampal CA1 long-term depression (LTD), and if so, whether it subsequently impacts hippocampal-dependent spatial memory. Here, we reported that LTD facilitated by elevated-platform stress in hippocampal slices was completely prevented by fluoxetine administration (10 mg/kg, i.p.) 30 min before stress. The LTD was not, however, significantly inhibited by fluoxetine administration immediately after stress. Similarly, fluoxetine incubation (10 μM) during electrophysiological recordings also displayed no influence on the stress-facilitated LTD. In addition, behavioral results showed that a single fluoxetine treatment 30 min before but not after acute stress fully reversed the impairment of spatial memory retrieval in the Morris water maze paradigm. Taken together, these results suggest that acute fluoxetine treatment only before, but not after stress, can prevent hippocampal CA1 LTD and spatial memory retrieval impairment caused by behavioral stress in adult animals.

  11. Enhancing Quality of Life of Families Who Use Adult Day Services: Short- and Long-Term Effects of the Adult Day Services Plus Program

    ERIC Educational Resources Information Center

    Gitlin, Laura N.; Reever, Karen; Dennis, Marie P.; Mathieu, Esther; Hauck, Walter W.

    2006-01-01

    Purpose: This study examined the short- and long-term effects of Adult Day Services Plus (ADS Plus), a low-cost care management intervention designed to enhance family caregiver well-being, increase service utilization, and decrease nursing home placement of impaired older adults enrolled in adult day care. Design and Methods: We used a…

  12. ETV, LT2 and You: How the Environmental Technology Verification Program Can Assist with the Long Term 2 Enhanced Surface Water Treatment Rule

    EPA Science Inventory

    The Environmental Technology Verification (ETV) Drinking Water Systems (DWS) Center has verified the performance of treatment technologies that may be used by communities in meeting the newly promulgated (2006) U.S. Environmental Protection Agency (USEPA) Long Term 2 Enhanced Sur...

  13. 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.…

  14. 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,…

  15. The Use of Interactive Computer Services to Enhance the Quality of Life for Long-Term Care Residents.

    ERIC Educational Resources Information Center

    McConatha, Douglas; And Others

    1994-01-01

    Examined and documented effects of interactive computer-based education and training on rehabilitation of long-term care residents (n=14). This approach was found to provide mental stimulation and challenge, as well as improving practical skills which directly impact upon competencies and feelings of autonomy of participants. (Author/NB)

  16. How Do Tests and Summary Writing Tasks Enhance Long-Term Retention of Students with Different Levels of Test Anxiety?

    ERIC Educational Resources Information Center

    Mok, Wilson Shun; Chan, Winnie Wai

    2016-01-01

    Testing has been found to facilitate students' long-term retention of information. However, the learning performance of highly test-anxious students can be impaired by tests. Thus, these students may learn ineffectively in a testing context. By contrast, summary writing may not trigger test anxiety and is therefore another learning strategy to…

  17. Long-term use of deferiprone significantly enhances left-ventricular ejection function in thalassemia major patients.

    PubMed

    Maggio, Aurelio; Vitrano, Angela; Lucania, Gaetano; Capra, Marcello; Cuccia, Liana; Gagliardotto, Francesco; Pitrolo, Lorella; Prossomariti, Luciano; Filosa, Aldo; Caruso, Vincenzo; Gerardi, Calogera; Campisi, Saveria; Cianciulli, Paolo; Rizzo, Michele; D'Ascola, Giuseppe; Ciancio, Angela; Di Maggio, Rosario; Calvaruso, Giuseppina; Pantalone, Gaetano Restivo; Rigano, Paolo

    2012-07-01

    A multicenter randomized open-label long-term sequential deferiprone–deferoxamine (DFP-DFO) versus DFP alone trial (sequential DFP-DFO) performed in patients with thalassemia major (TM) was retrospectively reanalyzed to assess the variation in the left ventricular ejection fraction (LVEF) [1].

  18. Protein Synthesis Inhibitors Did Not Interfere with Long-Term Depression Induced either Electrically in Juvenile Rats or Chemically in Middle-Aged Rats

    PubMed Central

    2016-01-01

    In testing the hypothesis that long-term potentiation (LTP) maintenance depends on triggered protein synthesis, we found no effect of protein synthesis inhibitors (PSIs) on LTP stabilization. Similarly, some studies reported a lack of effect of PSIs on long-term depression (LTD); the lack of effect on LTD has been suggested to be resulting from the short time recordings. If this proposal were true, LTD might exhibit sensitivity to PSIs when the recording intervals were enough long. We firstly induced LTD by a standard protocol involving low frequency stimulation, which is suitable for eliciting NMDAR-LTD in CA1 area of hippocampal slices obtained from juvenile Sprague-Dawley rats. This LTD was persistent for intervals in range of 8–10 h. Treating slices with anisomycin, however, did not interfere with the magnitude and persistence of this form of LTD. The failure of anisomycin to block synaptic-LTD might be relied on the age of animal, the type of protein synthesis inhibitors and/or the inducing protocol. To verify whether those variables altogether were determinant, NMDA or DHPG was used to chemically elicit LTD recorded up to 10 h on hippocampal slices obtained from middle-aged rats. In either form of LTD, cycloheximide did not interfere with LTD stabilization. Furthermore, DHPG application did show an increase in the global protein synthesis as assayed by radiolabeled methodology indicating that though triggered protein synthesis can occur but not necessarily required for LTD expression. The findings confirm that stabilized LTD in either juvenile, or middle-aged rats can be independent of triggered protein synthesis. Although the processes responsible for the independence of LTD stabilization on the triggered protein synthesis are not yet defined, these findings raise the possibility that de novo protein synthesis is not universally necessary. PMID:27517693

  19. Effect of low intensity low-frequency stimuli on long-term depression in the rat hippocampus area CA1 in vivo.

    PubMed

    Yang, Zhongfei; Zhang, Wencai; Wang, Ming; Ruan, Diyun; Chen, Jutao

    2012-08-08

    Normally long-term depression (LTD) is difficult to be induced in naïve adult rats in vivo, but it can be induced in the juvenile females and acute-stressed adult males. Using these rats as LTD models, we find in our previous study that LTD induction by the classical low-frequency stimuli (LFS) may be associated with sleep. During sleep, endogenous field potential oscillations presented in the neocortical and hippocampal circuits play important roles in synaptic downscaling as well as memory consolidations. Generally, LTD can be considered as a special synaptic downscaling and the classical LFS is very similar to such endogenous oscillations. Thus, we speculate whether we can design a new LFS which is more similar to such oscillations and whether LTD can be induced by it in naïve adult rats? In this study, we found that in the naïve adult rats anesthetized in sleep stage, the classical LFS could not induce LTD, however, a low-intensity LFS, an endogenous oscillation-like one, could induce LTD. Furthermore, in the rats anesthetized in wakefulness stage, neither the classical nor the low-intensity LFS could induce LTD. Our study showed that in the naïve adult rats, LTD could be induced by the oscillation-like LFS in the sleep stage anesthesia, suggesting that LTD may physiologically occur during sleep and be inhibited in wakefulness stage. Our study suggested that in the hippocampus LTD may be a potential long-term synaptic plasticity underlying sleep-dependent memory consolidations.

  20. Protein Synthesis Inhibitors Did Not Interfere with Long-Term Depression Induced either Electrically in Juvenile Rats or Chemically in Middle-Aged Rats.

    PubMed

    Abbas, Abdul-Karim

    2016-01-01

    In testing the hypothesis that long-term potentiation (LTP) maintenance depends on triggered protein synthesis, we found no effect of protein synthesis inhibitors (PSIs) on LTP stabilization. Similarly, some studies reported a lack of effect of PSIs on long-term depression (LTD); the lack of effect on LTD has been suggested to be resulting from the short time recordings. If this proposal were true, LTD might exhibit sensitivity to PSIs when the recording intervals were enough long. We firstly induced LTD by a standard protocol involving low frequency stimulation, which is suitable for eliciting NMDAR-LTD in CA1 area of hippocampal slices obtained from juvenile Sprague-Dawley rats. This LTD was persistent for intervals in range of 8-10 h. Treating slices with anisomycin, however, did not interfere with the magnitude and persistence of this form of LTD. The failure of anisomycin to block synaptic-LTD might be relied on the age of animal, the type of protein synthesis inhibitors and/or the inducing protocol. To verify whether those variables altogether were determinant, NMDA or DHPG was used to chemically elicit LTD recorded up to 10 h on hippocampal slices obtained from middle-aged rats. In either form of LTD, cycloheximide did not interfere with LTD stabilization. Furthermore, DHPG application did show an increase in the global protein synthesis as assayed by radiolabeled methodology indicating that though triggered protein synthesis can occur but not necessarily required for LTD expression. The findings confirm that stabilized LTD in either juvenile, or middle-aged rats can be independent of triggered protein synthesis. Although the processes responsible for the independence of LTD stabilization on the triggered protein synthesis are not yet defined, these findings raise the possibility that de novo protein synthesis is not universally necessary.

  1. PPARγ-induced upregulation of CD36 enhances hematoma resolution and attenuates long-term neurological deficits after germinal matrix hemorrhage in neonatal rats.

    PubMed

    Flores, Jerry J; Klebe, Damon; Rolland, William B; Lekic, Tim; Krafft, Paul R; Zhang, John H

    2016-03-01

    Germinal matrix hemorrhage remains the leading cause of morbidity and mortality in preterm infants in the United States with little progress made in its clinical management. Survivors are often afflicted with long-term neurological sequelae, including cerebral palsy, mental retardation, hydrocephalus, and psychiatric disorders. Blood clots disrupting normal cerebrospinal fluid circulation and absorption after germinal matrix hemorrhage are thought to be important contributors towards post-hemorrhagic hydrocephalus development. We evaluated if upregulating CD36 scavenger receptor expression in microglia and macrophages through PPARγ stimulation, which was effective in experimental adult cerebral hemorrhage models and is being evaluated clinically, will enhance hematoma resolution and ameliorate long-term brain sequelae using a neonatal rat germinal matrix hemorrhage model. PPARγ stimulation (15d-PGJ2) increased short-term PPARγ and CD36 expression levels as well as enhanced hematoma resolution, which was reversed by a PPARγ antagonist (GW9662) and CD36 siRNA. PPARγ stimulation (15d-PGJ2) also reduced long-term white matter loss and post-hemorrhagic ventricular dilation as well as improved neurofunctional outcomes, which were reversed by a PPARγ antagonist (GW9662). PPARγ-induced upregulation of CD36 in macrophages and microglia is, therefore, critical for enhancing hematoma resolution and ameliorating long-term brain sequelae.

  2. PPARγ-induced Upregulation of CD36 Enhances Hematoma Resolution and Attenuates Long-term Neurological Deficits after Germinal Matrix Hemorrhage in Neonatal Rats

    PubMed Central

    Flores, Jerry J.; Klebe, Damon; Rolland, William B.; Lekic, Tim; Krafft, Paul R.; Zhang, John H.

    2016-01-01

    Germinal matrix hemorrhage remains the leading cause of morbidity and mortality in preterm infants in the United States with little progress made in its clinical management. Survivors are often afflicted with long-term neurological sequelae, including cerebral palsy, mental retardation, hydrocephalus, and psychiatric disorders. Blood clots disrupting normal cerebrospinal fluid circulation and absorption after germinal matrix hemorrhage are thought to be important contributors towards post-hemorrhagic hydrocephalus development. We evaluated if upregulating CD36 scavenger receptor expression in microglia and macrophages through PPARγ stimulation, which was effective in experimental adult cerebral hemorrhage models and is being evaluated clinically, will enhance hematoma resolution and ameliorate long-term brain sequelae using a neonatal rat germinal matrix hemorrhage model. PPARγ stimulation (15d-PGJ2) increased short-term PPARγ and CD36 expression levels as well as enhanced hematoma resolution, which was reversed by a PPARγ antagonist (GW9662) and CD36 siRNA. PPARγ stimulation (15d-PGJ2) also reduced long-term white matter loss and post-hemorrhagic ventricular dilation as well as improved neurofunctional outcomes, which were reversed by a PPARγ antagonist (GW9662). PPARγ-induced upregulation of CD36 in macrophages and microglia is, therefore, critical for enhancing hematoma resolution and ameliorating long-term brain sequelae. PMID:26739391

  3. Using corporate governance to enhance 'long-term situation awareness' and assist in the avoidance of organisation-induced disasters.

    PubMed

    Siemieniuch, C E; Sinclair, M A

    2008-03-01

    This paper considers the issue of how corporate governance can and should deal with the long-term understanding of systems health-what we may call 'long-term situation awareness' (i.e. which evolves and is coherent over time) for organisational systems (and their component sub systems) in the engineering domain. Many characteristics affect long-term situation awareness-the rate of change to processes, pressures for greater efficiency from existing resources, changes in personnel, cultural changes and changes to the operational environment of the organisational systems. Many disasters (e.g. Chernobyl, Flixborough, Piper Alpha) have a causal path that indicates a loss of group situation awareness, over a long period of time. The problem of the gradual, slow drift over many years towards unsafe conduct of company operations is discussed and examples of possible consequences provided. A 'parable' from the world of manufacturing is used to exemplify the problem. The paper goes on to discuss some ways by which this problem could be addressed and longer-term system situational awareness increased; essentially by good corporate governance, knowledge management and ownership of processes. Links are made to the literature on these topics, and a route map to help organisations to gain the benefits is offered.

  4. Reproducible Volume Restoration and Efficient Long-term Volume Retention after Point-of-care Standardized Cell-enhanced Fat Grafting in Breast Surgery

    PubMed Central

    Dos Anjos, Severiano; Matas-Palau, Aina; Mercader, Josep; Katz, Adam J.

    2015-01-01

    Background: Lipoaspirated fat grafts are used to reconstruct volume defects in breast surgery. Although intraoperative treatment decisions are influenced by volume changes observed immediately after grafting, clinical effect and patient satisfaction are dependent on volume retention over time. The study objectives were to determine how immediate breast volume changes correlate to implanted graft volumes, to understand long-term adipose graft volume changes, and to study the “dose” effect of adding autologous stromal vascular fraction (SVF) cells to fat grafts on long-term volume retention. Methods: A total of 74 patients underwent 77 cell-enhanced fat grafting procedures to restore breast volume deficits associated with cosmetic and reconstructive indications. Although all procedures used standardized fat grafts, 21 of the fat grafts were enriched with a low dose of SVF cells and 56 were enriched with a high SVF cell dose. Three-dimensional imaging was used to quantify volume retention over time Results: For each milliliter of injected fat graft, immediate changes in breast volume were shown to be lower than the actual volume implanted for all methods and clinical indications treated. Long-term breast volume changes stabilize by 90–120 days after grafting. Final volume retention in the long-term was higher with high cell-enhanced fat grafts. Conclusions: Intraoperative immediate breast volume changes do not correspond with implanted fat graft volumes. In the early postoperative period (7–21 days), breast volume increases more than the implanted volume and then rapidly decreases in the subsequent 30–60 days. High-dose cell-enhanced fat grafts decrease early postsurgical breast edema and significantly improve long-term volume retention. PMID:26579353

  5. Glucocorticoid receptor activation lowers the threshold for NMDA-receptor-dependent homosynaptic long-term depression in the hippocampus through activation of voltage-dependent calcium channels.

    PubMed

    Coussens, C M; Kerr, D S; Abraham, W C

    1997-07-01

    The effects of the glucocorticoid receptor agonist RU-28362 on homosynaptic long-term depression (LTD) were examined in hippocampal slices obtained from adrenal-intact adult male rats. Field excitatory postsynaptic potentials were evoked by stimulation of the Schaffer collateral/commissural pathway and recorded in stratum radiatum of area CA1. Low-frequency stimulation (LFS) was delivered at LTD threshold (2 bouts of 600 pulses, 1 Hz, at baseline stimulation intensity). LFS of the Schaffer collaterals did not produce significant homosynaptic LTD in control slices. However, identical conditioning in the presence of the glucocorticoid receptor agonist RU-28362 (10 microM) produced a robust LTD, which was blocked by the selective glucocorticoid antagonist RU-38486. The LTD induced by glucocorticoid receptor activation was dependent on N-methyl-D-aspartate (NMDA) receptor activity, because the specific NMDA receptor antagonist D(-)-2-amino-5-phosphonopentanoic acid (D-AP5) blocked the facilitation. However, the facilitation of LTD was not due to a potentiation of the isolated NMDA receptor potential by RU-28362. The facilitation of LTD by RU-28362 was also blocked by coincubation of the L-type voltage-dependent calcium channel (VDCC) antagonist nimodipine. Selective activation of the L-type VDCCs by the agonist Bay K 8644 also facilitated LTD induction. Both nimodipine and D-AP5 were effective in blocking the facilitation of LTD by Bay K 8644. These results indicate that L-type VDCCs can contribute to NMDA-receptor-dependent LTD induction.

  6. The role of dendritic action potentials and Ca2+ influx in the induction of homosynaptic long-term depression in hippocampal CA1 pyramidal neurons.

    PubMed

    Christie, B R; Magee, J C; Johnston, D

    1996-01-01

    Long-term depression (LTD) of synaptic efficacy at CA1 synapses is believed to be a Ca(2+)-dependent process. We used high-speed fluorescence imaging and patch-clamp techniques to quantify the spatial distribution of changes in intracellular Ca2+ accompanying the induction of LTD at Schaffer collateral synapses in CA1 pyramidal neurons. Low-frequency stimulation (3 Hz), which was subthreshold for action potentials, produced small changes in [Ca2+]i and failed to elicit LTD. Increasing the stimulus strength so that action potentials were generated produced both robust LTD and increases in [Ca2+]i. Back-propagating action potentials at 3 Hz in the absence of synaptic stimulation also produced increases in [Ca2+]i, but failed to induce LTD. When subthreshold synaptic stimulation was paired with back-propagating action potentials, however, large increases in [Ca2+]i were observed and robust LTD was induced. The LTD was blocked by the N-methyl-D-aspartate receptor (NMDAr) antagonist APV, and stimulus-induced increases in [Ca2+]i were reduced throughout the neuron under these conditions. The LTD was also dependent on Ca2+ influx via voltage-gated Ca2+ channels (VGCCs), because LTD was severely attenuated or blocked by both nimodipine and Ni2+. These findings suggest that back-propagating action potentials can exert a powerful control over the induction of LTD and that both VGCCs and NMDArs are involved in the induction of this form of plasticity.

  7. miR-191 and miR-135 are required for long-lasting spine remodelling associated with synaptic long-term depression

    NASA Astrophysics Data System (ADS)

    Hu, Zhonghua; Yu, Danni; Gu, Qin-Hua; Yang, Yanqin; Tu, Kang; Zhu, Jun; Li, Zheng

    2014-02-01

    Activity-dependent modification of dendritic spines, subcellular compartments accommodating postsynaptic specializations in the brain, is an important cellular mechanism for brain development, cognition and synaptic pathology of brain disorders. NMDA receptor-dependent long-term depression (NMDAR-LTD), a prototypic form of synaptic plasticity, is accompanied by prolonged remodelling of spines. The mechanisms underlying long-lasting spine remodelling in NMDAR-LTD, however, are largely unclear. Here we show that LTD induction causes global changes in miRNA transcriptomes affecting many cellular activities. Specifically, we show that expression changes of miR-191 and miR-135 are required for maintenance but not induction of spine restructuring. Moreover, we find that actin depolymerization and AMPA receptor exocytosis are regulated for extended periods of time by miRNAs to support long-lasting spine plasticity. These findings reveal a miRNA-mediated mechanism and a role for AMPA receptor exocytosis in long-lasting spine plasticity, and identify a number of candidate miRNAs involved in LTD.

  8. Long-term depression-inducing stimuli promote cleavage of the synaptic adhesion molecule NGL-3 through NMDA receptors, matrix metalloproteinases and presenilin/γ-secretase

    PubMed Central

    Lee, Hyejin; Lee, Eun-Jae; Song, Yoo Sung; Kim, Eunjoon

    2014-01-01

    Long-term depression (LTD) reduces the functional strength of excitatory synapses through mechanisms that include the removal of AMPA glutamate receptors from the postsynaptic membrane. LTD induction is also known to result in structural changes at excitatory synapses, including the shrinkage of dendritic spines. Synaptic adhesion molecules are thought to contribute to the development, function and plasticity of neuronal synapses largely through their trans-synaptic adhesions. However, little is known about how synaptic adhesion molecules are altered during LTD. We report here that NGL-3 (netrin-G ligand-3), a postsynaptic adhesion molecule that trans-synaptically interacts with the LAR family of receptor tyrosine phosphatases and intracellularly with the postsynaptic scaffolding protein PSD-95, undergoes a proteolytic cleavage process. NGL-3 cleavage is induced by NMDA treatment in cultured neurons and low-frequency stimulation in brain slices and requires the activities of NMDA glutamate receptors, matrix metalloproteinases (MMPs) and presenilin/γ-secretase. These results suggest that NGL-3 is a novel substrate of MMPs and γ-secretase and that NGL-3 cleavage may regulate synaptic adhesion during LTD. PMID:24298159

  9. Failure to Recognize Novelty after Extended Methamphetamine Self-Administration Results from Loss of Long-Term Depression in the Perirhinal Cortex

    PubMed Central

    Scofield, Michael D; Trantham-Davidson, Heather; Schwendt, Marek; Leong, Kah-Chung; Peters, Jamie; See, Ronald E; Reichel, Carmela M

    2015-01-01

    Exposure to methamphetamine (meth) can produce lasting memory impairments in humans and rodents. We recently demonstrated that extended access meth self-administration results in novel object recognition (NOR) memory deficits in rats. Recognition of novelty depends upon intact perirhinal (pRh) cortex function, which is compromised by meth-induced downregulation of GluN2B-containing N-methyl-D-aspartate (NMDA) receptors. NMDA receptors containing this subunit have a critical role in pRh long-term depression (LTD), one of the primary physiological processes thought to underlie object recognition memory. We hypothesized that meth-induced downregulation of GluN2B receptors would compromise pRh LTD, leading to loss of NOR memory. We found that meth self-administration resulted in an inability to induce pRh LTD following 1 Hz stimulation, an effect that was reversed with bath application of the NMDA receptor partial agonist D-cycloserine (DCS). In addition, pRh microinfusion of DCS restored meth-induced memory deficits. Furthermore, blockade of GluN2B-containing NMDA receptors with Ro 25-6981 prevented DCS restoration of pRh LTD in meth subjects. Thus, targeting pRh LTD may be a promising strategy to treat meth-induced cognitive impairment. PMID:25865928

  10. Prophylactic efficacy of fluoxetine, escitalopram, sertraline, paroxetine, and concomitant psychotherapy in major depressive disorder: outcome after long-term follow-up.

    PubMed

    Peselow, Eric D; Tobia, Gabriel; Karamians, Reneh; Pizano, Demetria; IsHak, Waguih William

    2015-02-28

    The acute efficacy of selective serotonin reuptake inhibitors (SSRIs) in the treatment of major depressive disorder (MDD) is well established; however their role in longer-term prevention of recurrence remains unconfirmed. This study aims at examining: the prophylactic efficacy of four commonly used SSRIs in MDD in a naturalistic setting with long-term follow-up, the effect of concomitant cognitive behavioral therapy (CBT), and the predictors of outcome. In a prospective cohort study, 387 patients who either remitted or responded following treatment with four different SSRIs-fluoxetine, escitalopram, sertraline and paroxetine-were followed up over several years. During an average follow-up period of 34.5 months, 76.5% of patients experienced MDD recurrence. Escitalopram and fluoxetine showed a numerically higher prophylactic efficacy than paroxetine and sertraline but the difference was statistically insignificant. The prophylactic efficacy for SSRI-only treatment was limited, with a recurrence rate of 82.0%, compared to 59.0% of patient recurrence rate in concomitant Cognitive Behavioral Therapy (CBT). The relatively small size of the CBT group and the lack of randomization may undermine the extrapolation of its findings to clinical practice. Nevertheless, the study preliminary data may help in defining the clinical utility of antidepressants and CBT in the prophylaxis from MDD recurrence.

  11. Long-term deficiency of circulating and hippocampal insulin-like growth factor I induces depressive behavior in adult mice: A potential model of geriatric depression

    PubMed Central

    Mitschelen, Matthew; Yan, Han; Farley, Julie A.; Warrington, Junie P.; Han, Song; Hereñú, Claudia B.; Csiszar, Anna; Ungvari, Zoltan; Bailey-Downs, Lora C.; Bass, Caroline E.; Sonntag, William E.

    2011-01-01

    Numerous studies support the hypothesis that deficiency of insulin-like growth factor I (IGF-1) in adults contributes to depression, but direct evidence is limited. Many psychological and pro-cognitive effects have been attributed to IGF-1, but appropriate animal models of adult-onset IGF-1 deficiency are lacking. In this study, we use a viral-mediated Cre-loxP system to knockout the Igf1 gene in either the liver, neurons of the CA1 region of the hippocampus, or both. Knockout of liver Igf1 reduced serum IGF-1 levels by 40% and hippocampal IGF-1 levels by 26%. Knockout of Igf1 in CA1 reduced hippocampal IGF-1 levels by 13%. The most severe reduction in hippocampal IGF-1 occurred in the group with knockouts in both liver and CA1 (36% reduction), and was associated with a 3.5-fold increase in immobility in the forced swim test. Reduction of either circulating or hippocampal IGF-1 levels did not alter anxiety measured in an open field and elevated plus maze, nor locomotion in the open field. Furthermore, local compensation for deficiencies in circulating IGF-1 did not occur in the hippocampus, nor were serum levels of IGF-1 upregulated in response to the moderate decline of hippocampal IGF-1 caused by the knockouts in CA1. We conclude that adult-onset IGF-1 deficiency alone is sufficient to induce a depressive phenotype in mice. Furthermore, our results suggest that individuals with low brain levels of IGF-1 are at increased risk for depression and these behavioral effects are not ameliorated by increased local IGF-1 production or transport. Our study supports the hypothesis that the natural IGF-1 decline in aging humans may contribute to geriatric depression. PMID:21524689

  12. Improved Long-Term Memory via Enhancing cGMP-PKG Signaling Requires cAMP-PKA Signaling

    PubMed Central

    Bollen, Eva; Puzzo, Daniela; Rutten, Kris; Privitera, Lucia; De Vry, Jochen; Vanmierlo, Tim; Kenis, Gunter; Palmeri, Agostino; D'Hooge, Rudi; Balschun, Detlef; Steinbusch, Harry MW; Blokland, Arjan; Prickaerts, Jos

    2014-01-01

    Memory consolidation is defined by the stabilization of a memory trace after acquisition, and consists of numerous molecular cascades that mediate synaptic plasticity. Commonly, a distinction is made between an early and a late consolidation phase, in which early refers to the first hours in which labile synaptic changes occur, whereas late consolidation relates to stable and long-lasting synaptic changes induced by de novo protein synthesis. How these phases are linked at a molecular level is not yet clear. Here we studied the interaction of the cyclic nucleotide-mediated pathways during the different phases of memory consolidation in rodents. In addition, the same pathways were studied in a model of neuronal plasticity, long-term potentiation (LTP). We demonstrated that cGMP/protein kinase G (PKG) signaling mediates early memory consolidation as well as early-phase LTP, whereas cAMP/protein kinase A (PKA) signaling mediates late consolidation and late-phase-like LTP. In addition, we show for the first time that early-phase cGMP/PKG signaling requires late-phase cAMP/PKA-signaling in both LTP and long-term memory formation. PMID:24813825

  13. Spatial performance in a complex maze is associated with persistent long-term potentiation enhancement in mouse hippocampal slices at early training stages.

    PubMed

    Lange-Asschenfeldt, C; Lohmann, P; Riepe, M W

    2007-06-29

    Long-term potentiation (LTP) and long-term depression (LTD) are principal reflections of synaptic plasticity that have been implicated in learning and memory. We have previously shown that spatial learning in a newly validated complex maze is accompanied by depression of hippocampal CA1 synaptic activity in hippocampal slices of trained mice ("behavioral LTD"). In the present study, we investigated whether behavioral LTD is accompanied by alterations of subsequent LTP induced by high-frequency stimulation (HFS). Moreover, we were interested in the time course of such alterations in relation to training stage. Animals underwent 1, 2, and 8 days of spatial training in the complex maze, respectively. Hippocampal slices were taken 24 h after the last training session. We found a simultaneous decrease of basal synaptic response and increase of HFS induced LTP magnitude compared with slices of untrained animals. Synaptic plasticity was not influenced by repeated running wheel exercise in an additional control group without spatial learning. The mentioned alterations occurred already after day 2 of maze exploration parallel to the most pronounced improvement of behavioral performance but did not change thereafter until day 8 despite further learning progress. They were also found when animals were trained for 2 days and kept at rest for a subsequent 6 days. In conclusion, spatial learning may be reflected by distinct and persistent measurable alterations of synaptic plasticity in hippocampal CA1 neurons at early training stages.

  14. A novel bio-mimicking, planar nano-edge microelectrode enables enhanced long-term neural recording

    NASA Astrophysics Data System (ADS)

    Wijdenes, Pierre; Ali, Hasan; Armstrong, Ryden; Zaidi, Wali; Dalton, Colin; Syed, Naweed I.

    2016-10-01

    Our inability to accurately monitor individual neurons and their synaptic activity precludes fundamental understanding of brain function under normal and various pathological conditions. However, recent breakthroughs in micro- and nano-scale fabrication processes have advanced the development of neuro-electronic hybrid technology. Among such devices are three-dimensional and planar electrodes, offering the advantages of either high fidelity or longer-term recordings respectively. Here, we present the next generation of planar microelectrode arrays with “nano-edges” that enable long-term (≥1 month) and high fidelity recordings at a resolution 15 times higher than traditional planar electrodes. This novel technology enables better understanding of brain function and offers a tremendous opportunity towards the development of future bionic hybrids and drug discovery devices.

  15. A novel bio-mimicking, planar nano-edge microelectrode enables enhanced long-term neural recording

    PubMed Central

    Wijdenes, Pierre; Ali, Hasan; Armstrong, Ryden; Zaidi, Wali; Dalton, Colin; Syed, Naweed I.

    2016-01-01

    Our inability to accurately monitor individual neurons and their synaptic activity precludes fundamental understanding of brain function under normal and various pathological conditions. However, recent breakthroughs in micro- and nano-scale fabrication processes have advanced the development of neuro-electronic hybrid technology. Among such devices are three-dimensional and planar electrodes, offering the advantages of either high fidelity or longer-term recordings respectively. Here, we present the next generation of planar microelectrode arrays with “nano-edges” that enable long-term (≥1 month) and high fidelity recordings at a resolution 15 times higher than traditional planar electrodes. This novel technology enables better understanding of brain function and offers a tremendous opportunity towards the development of future bionic hybrids and drug discovery devices. PMID:27731326

  16. Long-Term Efficacy of Methylphenidate in Enhancing Attention Regulation, Social Skills, and Academic Abilities of Childhood Cancer Survivors

    PubMed Central

    Conklin, Heather M.; Reddick, Wilburn E.; Ashford, Jason; Ogg, Susan; Howard, Scott C.; Morris, E. Brannon; Brown, Ronald; Bonner, Melanie; Christensen, Robbin; Wu, Shengjie; Xiong, Xiaoping; Khan, Raja B.

    2010-01-01

    Purpose Methylphenidate (MPH) ameliorates attention problems experienced by some cancer survivors in the short term, but its long-term efficacy is unproven. Patients and Methods This study investigates the long-term effectiveness of maintenance doses of MPH in survivors of childhood brain tumors (n = 35) and acute lymphoblastic leukemia (n = 33) participating in a 12-month MPH trial. Measures of attention (Conners' Continuous Performance Test [CPT], Conners' Rating Scales [CRS]), academic abilities (Wechsler Individual Achievement Test [WIAT]), social skills (Social Skills Rating System [SSRS]), and behavioral problems (Child Behavior Checklist [CBCL]) were administered at premedication baseline and at the end of the MPH trial while on medication. A cancer control group composed of patients who were not administered MPH (brain tumor = 31 and acute lymphoblastic leukemia = 23) was assessed on the same measures 2 months apart. Results For the MPH group, repeated measures analysis of variance revealed significant improvement in performance on a measure of sustained attention (CPT indices, P < .05); parent, teacher, and self-report ratings of attention (CRS indices, P < .05), and parent ratings of social skills or behavioral problems (SSRS and CBCL indices; P < .05). In contrast, the cancer control group only showed improvement on parent ratings of attention (Conners' Parent Rating Scale indices; P < .05) and social skills (SSRS and CBCL indices; P < .05). There was no significant improvement on the academic measure (WIAT) in either group. Conclusion Attention and behavioral benefits of MPH for childhood cancer survivors are maintained across settings over the course of a year. Although academic gains were not identified, MPH may offer benefits in academic areas not assessed. PMID:20837955

  17. Acid-sensing ion channel 1a is required for mGlu receptor dependent long-term depression in the hippocampus.

    PubMed

    Mango, D; Braksator, E; Battaglia, G; Marcelli, S; Mercuri, N B; Feligioni, M; Nicoletti, F; Bashir, Z I; Nisticò, R

    2017-01-27

    Acid-sensing ion channels (ASICs), members of the degenerin/epithelial Na(+) channel superfamily, are widely distributed in the mammalian nervous system. ASIC1a is highly permeable to Ca(2+) and are thought to be important in a variety of physiological processes, including synaptic plasticity, learning and memory. To further understand the role of ASIC1a in synaptic transmission and plasticity, we investigated metabotropic glutamate (mGlu) receptor-dependent long-term depression (LTD) in the hippocampus. We found that ASIC1a channels mediate a component of LTD in P30-40 animals, since the ASIC1a selective blocker psalmotoxin-1 (PcTx1) reduced the magnitude of LTD induced by application of the group I mGlu receptor agonist (S)-3,5-Dihydroxyphenylglycine (DHPG) or induced by paired-pulse low frequency stimulation (PP-LFS). Conversely, PcTx1 did not affect LTD in P13-18 animals. We also provide evidence that ASIC1a is involved in group I mGlu receptor-induced increase in action potential firing. However, blockade of ASIC1a did not affect DHPG-induced polyphosphoinositide hydrolysis, suggesting the involvement of some other molecular partners in the functional crosstalk between ASIC1a and group I mGlu receptors. Notably, PcTx1 was able to prevent the increase in GluA1 S845 phosphorylation at the post-synaptic membrane induced by group I mGlu receptor activation. These findings suggest a novel function of ASIC1a channels in the regulation of group I mGlu receptor synaptic plasticity and intrinsic excitability.

  18. Gene-environment interactions affect long-term depression (LTD) through changes in dopamine receptor affinity in Snap25 deficient mice

    PubMed Central

    Baca, Michael; Allan, Andrea M.; Partridge, L. Donald; Wilson, Michael C.

    2013-01-01

    Genes and environmental conditions interact in the development of cognitive capacities and each plays an important role in neuropsychiatric disorders such as attention deficit/hyperactivity disorder (ADHD) and schizophrenia. Multiple studies have indicated that the gene for the SNARE protein SNAP-25 is a candidate susceptibility gene for ADHD, as well as schizophrenia, while maternal smoking is a candidate environmental risk factor for ADHD. We utilized mice heterozygous for a Snap25 null allele and deficient in SNAP-25 expression to model genetic effects in combination with prenatal exposure to nicotine to explore genetic and environmental interactions in synaptic plasticity and behavior. We show that SNAP-25 deficient mice exposed to prenatal nicotine exhibit hyperactivity and deficits in social interaction. Using a high frequency stimulus electrophysiological paradigm for long-term depression (LTD) induction, we examined the roles of dopaminergic D2 receptors (D2Rs) and cannabinoid CB1 receptors (CB1Rs), both critical for LTD induction in the striatum. We found that prenatal exposure to nicotine in Snap25 heterozygote null mice produced a deficit in the D2R-dependent induction of LTD, although CB1R regulation of plasticity was not impaired. We also show that prenatal nicotine exposure altered the affinity and/or receptor coupling of D2Rs, but not the number of these receptors in heterozygote null Snap25 mutants. These results refine the observations made in the coloboma mouse mutant, a proposed mouse model of ADHD, and illustrate how gene × environmental influences can interact to perturb neural functions that regulate behavior. PMID:23939223

  19. Chronic intermittent alcohol disrupts the GluN2B-associated proteome and specifically regulates group I mGlu receptor-dependent long-term depression.

    PubMed

    Wills, Tiffany A; Baucum, Anthony J; Holleran, Katherine M; Chen, Yaoyi; Pasek, Johanna G; Delpire, Eric; Tabb, David L; Colbran, Roger J; Winder, Danny G

    2017-03-01

    N-Methyl-d-aspartate receptors (NMDARs) are major targets of both acute and chronic alcohol, as well as regulators of plasticity in a number of brain regions. Aberrant plasticity may contribute to the treatment resistance and high relapse rates observed in alcoholics. Recent work suggests that chronic alcohol treatment preferentially modulates both the expression and subcellular localization of NMDARs containing the GluN2B subunit. Signaling through synaptic and extrasynaptic GluN2B-NMDARs has already been implicated in the pathophysiology of various other neurological disorders. NMDARs interact with a large number of proteins at the glutamate synapse, and a better understanding of how alcohol modulates this proteome is needed. We employed a discovery-based proteomic approach in subcellular fractions of hippocampal tissue from chronic intermittent alcohol (CIE)-exposed C57Bl/6J mice to gain insight into alcohol-induced changes in GluN2B signaling complexes. Protein enrichment analyses revealed changes in the association of post-synaptic proteins, including scaffolding, glutamate receptor and PDZ-domain binding proteins with GluN2B. In particular, GluN2B interaction with metabotropic glutamate (mGlu)1/5 receptor-dependent long-term depression (LTD)-associated proteins such as Arc and Homer 1 was increased, while GluA2 was decreased. Accordingly, we found a lack of mGlu1/5 -induced LTD while α1 -adrenergic receptor-induced LTD remained intact in hippocampal CA1 following CIE. These data suggest that CIE specifically disrupts mGlu1/5 -LTD, representing a possible connection between NMDAR and mGlu receptor signaling. These studies not only demonstrate a new way in which alcohol can modulate plasticity in the hippocampus but also emphasize the utility of this discovery-based proteomic approach to generate new hypotheses regarding alcohol-related mechanisms.

  20. Long-term effects of nicotine on the forced swimming test in mice: an experimental model for the study of depression caused by smoke.

    PubMed

    Mannucci, Carmen; Tedesco, Michele; Bellomo, Maria; Caputi, Achille P; Calapai, Gioacchino

    2006-10-01

    Large evidence showing an association between depression and tobacco smoking is known. Nicotine is the active chemical responsible for smoking addiction, and its withdrawal may induce in smokers greater sensitivity to stress. Our aim has been to investigate the links between tobacco addiction and depression by studying the long-term effects of repeated administration of nicotine followed by dependence, to forced swimming test, serotonin content and 5-HT(1A) expression in diencephalon. Dependence has been induced by daily subcutaneous injection in mice of nicotine (2mg/kg four injections daily) for 15 days and assessed after nicotine withdrawal with an abstinence scale; control animals received daily subcutaneous injection of saline for the same period. Experiments on forced swimming test have been carried out at t=0 (last day of nicotine or saline treatment), and 15, 30, 45 and 60 days after saline or nicotine withdrawal. Both control mice and nicotine mice have been pre-treated with oral 5-hydroxy-tryptophan (12.5-50mg/kg), precursor of serotonin, before forced swimming test. Nicotine mice have shown on forced swimming test a significant increase of immobility time compared to control mice. This increase was not evident in nicotine mice treated with 5-hydroxy-tryptophan and treatment with the selective serotonin receptorial antagonist WAY 100635 (WAY) abolished 5-hydroxy-tryptophan effects. Evaluation of diencephalic serotonin, performed at t=0 showed an increase of diencephalic serotonin content, while serotonin measured 15, 30, 45 and 60 days after nicotine withdrawal, was significantly reduced in nicotine mice compared to control mice. Western blot analysis showed a great reduction of 5-HT(1A) receptor expression in nicotine mice measured at t=0 (last day of treatment) and at 15 and 30 days after nicotine withdrawal compared to control mice. Our results show that (i) behavioural alterations estimated with forced swimming test and (ii) changes in diencephalic

  1. Combining long term field experiments and nanoscale analysis to enhance process understanding of root litter stabilization by mineral interactions

    NASA Astrophysics Data System (ADS)

    Chabbi, Abad; Baumann, Karen; Remusat, Laurent; Barre, Pierre; Dignac, Marie-France; Rumpel, Cornelia

    2015-04-01

    Mineral interaction may affect the stabilisation of root litter directly or indirectly after microbial decomposition and transformation. The importance of both processes may vary within the soil profile. In this study we studied C stabilisation of isotopically labelled root litter (13C and 15N), which was incubated during 3 year in the field at different soil depth. Samples from this field experiment were recovered and subjected to nanoscale analyses in order to elucidate mineral interactions occurring in different parts of the soil profile. Our results showed enrichment of mineral associated organic matter in subsoil horizons. However, material derived from new plant litter may be stabilised at similar rates in top- and subsoil horizons. N-containing compounds are enriched in the mineral associated fraction of subsoil horizons, indicating enrichment of microbial derived material with depth. Nano scale analyses showed that indeed plant-derived material may be associated with metal oxides in topsoil horizons, whereas the mineral associated organic matter in subsoil horizons may consist of microbial cells. Interestingly, in contrast to short term laboratory analysis, decoupling of C and N through stabilisation with soil minerals was observed during this long term field experiment. Our results indicate that the nature of OM stabilised by mineral interactions is depth specific. Therefore, we suggest, that plant derived lignocellulosic material may be preserved by mineral interactions in topsoil given its incomplete degradation, thereby leading to the formation of functional groups and favouring adsorption to soil minerals. This is consistent with the higher state of lignin-degradation observed in topsoil horizons as compared to subsoil. At depth, where microorganisms are most likely energy limited, degradation of fresh plant litter may be complete, thereby diminishing the formation of lignocellulosic compounds capable of sorption onto metal oxides. As a result

  2. Trophic interactions of fish communities at midwater depths enhance long-term carbon storage and benthic production on continental slopes.

    PubMed

    Trueman, C N; Johnston, G; O'Hea, B; MacKenzie, K M

    2014-07-22

    Biological transfer of nutrients and materials between linked ecosystems influences global carbon budgets and ecosystem structure and function. Identifying the organisms or functional groups that are responsible for nutrient transfer, and quantifying their influence on ecosystem structure and carbon capture is an essential step for informed management of ecosystems in physically distant, but ecologically linked areas. Here, we combine natural abundance stable isotope tracers and survey data to show that mid-water and bentho-pelagic-feeding demersal fishes play an important role in the ocean carbon cycle, bypassing the detrital particle flux and transferring carbon to deep long-term storage. Global peaks in biomass and diversity of fishes at mid-slope depths are explained by competitive release of the demersal fish predators of mid-water organisms, which in turn support benthic fish production. Over 50% of the biomass of the demersal fish community at depths between 500 and 1800 m is supported by biological rather than detrital nutrient flux processes, and we estimate that bentho-pelagic fishes from the UK-Irish continental slope capture and store a volume of carbon equivalent to over 1 million tonnes of CO2 every year.

  3. Micronutrients on the Menu: Enhancing the Quality of Food in Long-term Care for Regular, Nontherapeutic Menus.

    PubMed

    Lam, Ivy T; Keller, Heather H; Duizer, Lisa; Stark, Ken

    2015-06-01

    Micronutrient (vitamin and mineral) deficiencies may exacerbate prevalent health conditions occurring in long-term care (LTC) residents, and current food provision may potentiate this problem. A micronutrient-focused, food-first approach to menu planning may address this gap by emphasizing nutrient-dense foods. The objectives were to determine if: (i) selected LTC menus met micronutrient and Canada's Food Guide (CFG) recommendations, and (ii) recommendations can be met through food alone with strategic menu planning. Regular, nontherapeutic menus (week 1, all meals) from diverse LTC homes (n = 5) across Canada were analyzed for micronutrient content using Food Processor and CFG servings. Site dietitians confirmed menu analyses. Five super-menus were created and analyzed for comparison. The nutrient content of the menus varied significantly across homes. Micronutrients of greatest concern were (mean ± SD) vitamin D (8.90 ± 5.29 µg/d) and vitamin E (5.13 ± 1.74 mg/d). Folate, magnesium, and potassium were also below recommendations. Super-menus of equal food volume met recommendations for all micronutrients except vitamin D (56%), vitamin E (84%), and potassium (85%). Meeting most micronutrient recommendations is possible with creative and deliberate menu planning. Knowledge translation of best practices is needed.

  4. Trophic interactions of fish communities at midwater depths enhance long-term carbon storage and benthic production on continental slopes

    PubMed Central

    Trueman, C. N.; Johnston, G.; O'Hea, B.; MacKenzie, K. M.

    2014-01-01

    Biological transfer of nutrients and materials between linked ecosystems influences global carbon budgets and ecosystem structure and function. Identifying the organisms or functional groups that are responsible for nutrient transfer, and quantifying their influence on ecosystem structure and carbon capture is an essential step for informed management of ecosystems in physically distant, but ecologically linked areas. Here, we combine natural abundance stable isotope tracers and survey data to show that mid-water and bentho-pelagic-feeding demersal fishes play an important role in the ocean carbon cycle, bypassing the detrital particle flux and transferring carbon to deep long-term storage. Global peaks in biomass and diversity of fishes at mid-slope depths are explained by competitive release of the demersal fish predators of mid-water organisms, which in turn support benthic fish production. Over 50% of the biomass of the demersal fish community at depths between 500 and 1800 m is supported by biological rather than detrital nutrient flux processes, and we estimate that bentho-pelagic fishes from the UK–Irish continental slope capture and store a volume of carbon equivalent to over 1 million tonnes of CO2 every year. PMID:24898373

  5. Short- and long-term response of deteriorating brackish marshes and open-water ponds to sediment enhancement by thin-layer dredge disposal

    USGS Publications Warehouse

    La Peyre, M.K.; Gossman, B.; Piazza, Bryan P.

    2009-01-01

    Artificial sediment enhancement using a thin layer of dredged material has been suggested as a means to increase elevation and create soil conditions conducive to increased marsh structure and function in deteriorating marshes. Using a chronosequence approach, we examined the effects of sediment enhancement in deteriorating marsh and open-water pond habitats located in six brackish marshes. Sediment enhancement of both marsh and interior pond sites had significant, immediate, and long-lasting effects on physical soil properties and nutrient status with increased bulk density and inorganic nitrogen. Vegetative cover and productivity response were minimal for deteriorating vegetated marshes with the short-term response data showing no significant impact of sediment enhancement and long-term trends indicating decreasing productivity over time. In contrast, trajectory models of vegetative cover and productivity in interior pond sites showed increases over time indicating that, for restoration of interior ponds, sediment enhancement may prove valuable. The use of trajectory models emphasizes the need for long-term monitoring to determine restoration success of projects. ?? 2008 U.S. Government.

  6. Enhanced long-term strength and durability of shotcrete with high-strength C{sub 12}A{sub 7} mineral-based accelerator

    SciTech Connect

    Won, Jong-Pil Hwang, Un-Jong; Lee, Su-Jin

    2015-10-15

    This study evaluated the performance of shotcrete using high strength C{sub 12}A{sub 7} mineral-based accelerator that has been developed to improve the durability and long-term strength. Rebound, compressive strength and flexural strength were tested in the field. Test result showed that existing C{sub 12}A{sub 7} mineral-based accelerator exhibits better early strength than the high-strength C{sub 12}A{sub 7} mineral-based accelerator until the early age, but high-strength C{sub 12}A{sub 7} mineral-based accelerator shows about 29% higher at the long-term age of 28 days. Microstructural analysis such as scanning electron microscope (SEM), X-ray diffraction (XRD) and nitrogen adsorption method was evaluated to analyze long-term strength development mechanism of high strength C{sub 12}A{sub 7} mineral-based accelerator. As analysis result, it had more dense structure due to the reaction product by adding material that used to enhanced strength. It had better resistance performance in chloride ion penetration, freezing–thawing and carbonation than shotcrete that used existing C{sub 12}A{sub 7} mineral-based accelerator.

  7. Ganzfeld Stimulation or Sleep Enhance Long Term Motor Memory Consolidation Compared to Normal Viewing in Saccadic Adaptation Paradigm

    PubMed Central

    Voges, Caroline; Helmchen, Christoph; Heide, Wolfgang; Sprenger, Andreas

    2015-01-01

    Adaptation of saccade amplitude in response to intra-saccadic target displacement is a type of implicit motor learning which is required to compensate for physiological changes in saccade performance. Once established trials without intra-saccadic target displacement lead to de-adaptation or extinction, which has been attributed either to extra-retinal mechanisms of spatial constancy or to the influence of the stable visual surroundings. Therefore we investigated whether visual deprivation (“Ganzfeld”-stimulation or sleep) can partially maintain this motor learning compared to free viewing of the natural surroundings. Thirty-five healthy volunteers performed two adaptation blocks of 100 inward adaptation trials – interspersed by an extinction block – which were followed by a two-hour break with or without visual deprivation (VD). Using additional adaptation and extinction blocks short and long (4 weeks) term memory of this implicit motor learning were tested. In the short term, motor memory tested immediately after free viewing was superior to adaptation performance after VD. In the long run, however, effects were opposite: motor memory and relearning of adaptation was superior in the VD conditions. This could imply independent mechanisms that underlie the short-term ability of retrieving learned saccadic gain and its long term consolidation. We suggest that subjects mainly rely on visual cues (i.e., retinal error) in the free viewing condition which makes them prone to changes of the visual stimulus in the extinction block. This indicates the role of a stable visual array for resetting adapted saccade amplitudes. In contrast, visual deprivation (GS and sleep), might train subjects to rely on extra-retinal cues, e.g., efference copy or prediction to remap their internal representations of saccade targets, thus leading to better consolidation of saccadic adaptation. PMID:25867186

  8. Enhanced Long-Term Brain Magnetic Resonance Imaging Evaluation of Children with Sickle Cell Disease after Hematopoietic Cell Transplantation.

    PubMed

    Green, Nancy S; Bhatia, Monica; Griffith, Erica Y; Qureshi, Mahvish; Briamonte, Courtney; Savone, Mirko; Sands, Stephen; Lee, Margaret T; Lignelli, Angela; Brickman, Adam M

    2017-04-01

    Progressive neurovasculopathy in children with sickle cell disease (SCD) results in decreased cognitive function and quality of life (QoL). Hematopoietic cell transplantation (HCT) is believed to halt progression of neurovasculopathy. Quantitative analysis of T2-weighted fluid attenuated inversion recovery (FLAIR) magnetic resonance imaging (MRI) for white matter hyperintensity (WMH) burden provides a meaningful estimate of small vessel cerebrovascular disease. We asked if quantitative analysis of WMH could complement standardized clinical assessment of MRI/magnetic resonance angiography (MRA) for assessing SCD central nervous system vasculopathy before and after HCT. Retrospective longitudinal clinical examination of scheduled annual MRI/MRA and quantitative analysis of WMH were performed before and 1 to 7 years after HCT at scheduled annual intervals, along with QoL measurements, in children who had engrafted after HCT. Of 18 patients alive and persistently engrafted (median age, 9.1 years), pretransplantation MRI demonstrated that 9 and 5 had sickle-related stroke and/or small infarcts, respectively. Patients were divided into WMH severity tertiles based on pretransplantation WMH volumes. MRI and WMH were assessed 1 to 7 years after HCT. MRI/MRA and WMH volume were stable or slightly better in 17 of 18 patients. By parent- and self-report, post-HCT QoL improved for children in the lowest WMH tertile significantly more than in the other groups. Based on this single-institution retrospective sample, we report that WMH appears to quantitatively support MRI-based findings that HCT stabilizes long-term small and large vessel cerebrovascular changes and is associated with the degree of improved QoL. While confirmation in larger prospective studies and evaluation by neurocognitive testing are needed, these findings suggest that WMH is a useful biomarker of neurovasculopathy after transplantation for SCD.

  9. Long-term exposure to diesel exhaust enhances antigen-induced eosinophilic inflammation and epithelial damage in the murine airway.

    PubMed

    Ichinose, T; Takano, H; Miyabara, Y; Sagai, M

    1998-07-01

    The histopathologic changes in the murine airway induced by long-term exposure to diesel exhaust (DE), ovalbumin (OA), or both were investigated. The relationship between the histopathologic appearances in the airway and immunoglobulin production or local cytokine levels in the lungs was also studied. ICR mice were exposed to clean air or DE at a soot concentrations of 0.3, 1.0, or 3.0 mg/m3 for 34 weeks. Fifteen weeks after exposure to DE, mice were sensitized intraperitoneally with 10 micrograms of OA and challenged by an aerosol of 1% OA six times at 3-week intervals during the last 18 weeks of the exposure. DE exposure caused a dose-dependent increase of nonciliated cell proliferation and epithelial cell hypertrophy in the airway, but showed no effect on goblet cell proliferation in the bronchial epithelium and eosinophil recruitment in the submucosa of the airway. OA treatment induced very slight changes in goblet cell proliferation and eosinophil recruitment. The combination of OA and DE exposure produced dose-dependent increases of goblet cells and eosinophils, in addition to further increases of the typical changes induced by DE. OA treatment induced OA-specific IgG1 and IgE production in plasma, whereas the adjuvant effects of DE exposure on immunoglobulin production were not observed. Inhalation of DE led to increased levels of IL-5 protein in the lung at a soot concentration of 1.0 and 3.0 mg/m3 with OA, although these increases did not reach statistical significance. We conclude that the combination of antigen and chronic exposure to DE produces increased eosinophilic inflammation, and cell damage to the epithelium may depend on the degree of eosinophilic inflammation in the airway.

  10. Effects of resistance and all-round, functional training on quality of life, vitality and depression of older adults living in long-term care facilities: a 'randomized' controlled trial [ISRCTN87177281

    PubMed Central

    Chin A Paw, Marijke JM; van Poppel, Mireille NM; Twisk, Jos WR; van Mechelen, Willem

    2004-01-01

    Background Regular physical activity may improve different aspects of wellbeing in older people, such as quality of life, vitality and depression. However, there is little experimental evidence to support this assumption. Therefore, we examined the effect of different training protocols on quality of life, vitality and depression of older adults living in long-term care facilities. Methods Subjects (n = 173, aged 64 to 94 years, living in long-term care facilities), were randomized to six months of three different moderate-intensity group exercise training protocols, or to an 'educational' control condition. Exercise consisted of two 45–60-minute training sessions per week of 1) resistance training; 2) all-round, functional training; or 3) a combination of both. Perceived health, the Geriatric Depression Scale (GDS), the Vitality Plus Scale (VPS) and the Dementia Quality of Life questionnaire (DQoL) were administered at baseline and after six months. Results In the combined training group a small but significant decline was seen in perceived health, DQoL and VPS score compared to the control group. Conclusions We conclude that neither strength training nor all-round, functional training of moderate intensity is effective in improving quality of life, vitality or depression of older people living in long-term care facilities. PMID:15233841

  11. Activation of the basolateral amygdala induces long-term enhancement of specific memory representations in the cerebral cortex.

    PubMed

    Chavez, Candice M; McGaugh, James L; Weinberger, Norman M

    2013-03-01

    The basolateral amygdala (BLA) modulates memory, particularly for arousing or emotional events, during post-training periods of consolidation. It strengthens memories whose substrates in part or whole are stored remotely, in structures such as the hippocampus, striatum and cerebral cortex. However, the mechanisms by which the BLA influences distant memory traces are unknown, largely because of the need for identifiable target mnemonic representations. Associative tuning plasticity in the primary auditory cortex (A1) constitutes a well-characterized candidate specific memory substrate that is ubiquitous across species, tasks and motivational states. When tone predicts reinforcement, the tuning of cells in A1 shifts toward or to the signal frequency within its tonotopic map, producing an over-representation of behaviorally important sounds. Tuning shifts have the cardinal attributes of forms of memory, including associativity, specificity, rapid induction, consolidation and long-term retention and are therefore likely memory representations. We hypothesized that the BLA strengthens memories by increasing their cortical representations. We recorded multiple unit activity from A1 of rats that received a single discrimination training session in which two tones (2.0 s) separated by 1.25 octaves were either paired with brief electrical stimulation (400 ms) of the BLA (CS+) or not (CS-). Frequency response areas generated by presenting a matrix of test tones (0.5-53.82 kHz, 0-70 dB) were obtained before training and daily for 3 weeks post-training. Tuning both at threshold and above threshold shifted predominantly toward the CS+ beginning on day 1. Tuning shifts were maintained for the entire 3 weeks. Absolute threshold and bandwidth decreased, producing less enduring increases in sensitivity and selectivity. BLA-induced tuning shifts were associative, highly specific and long-lasting. We propose that the BLA strengthens memory for important experiences by increasing the

  12. Visual Input Enhancement via Essay Coding Results in Deaf Learners' Long-Term Retention of Improved English Grammatical Knowledge

    ERIC Educational Resources Information Center

    Berent, Gerald P.; Kelly, Ronald R.; Schmitz, Kathryn L.; Kenney, Patricia

    2009-01-01

    This study explored the efficacy of visual input enhancement, specifically "essay enhancement", for facilitating deaf college students' improvement in English grammatical knowledge. Results documented students' significant improvement immediately after a 10-week instructional intervention, a replication of recent research. Additionally, the…

  13. Life Stress and the Long-Term Treatment Course of Recurrent Depression: III. Nonsevere Life Events Predict Recurrence for Medicated Patients over 3 Years

    ERIC Educational Resources Information Center

    Monroe, Scott M.; Torres, Leandro D.; Guillaumot, Julien; Harkness, Kate L.; Roberts, John E.; Frank, Ellen; Kupfer, David

    2006-01-01

    Research has consistently documented the significance of severe life events for onset of major depression. Theory, however, suggests other forms of stress are relevant for depression's recurrence. Nonsevere life events were tested in relation to depression for 126 patients with recurrent depression in a 3-year randomized maintenance protocol. Life…

  14. 77 FR 57545 - Long Term 2 Enhanced Surface Water Treatment Rule: Public Meeting on Monitoring Data Analysis...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-09-18

    ... enhanced analytical methods. The third topic is the effectiveness of Escherichia coli as a screen to... treatment that may be needed based on the occurrence of Cryptosporidium or E. coli in their source...

  15. Visual input enhancement via essay coding results in deaf learners' long-term retention of improved English grammatical knowledge.

    PubMed

    Berent, Gerald P; Kelly, Ronald R; Schmitz, Kathryn L; Kenney, Patricia

    2009-01-01

    This study explored the efficacy of visual input enhancement, specifically essay enhancement, for facilitating deaf college students' improvement in English grammatical knowledge. Results documented students' significant improvement immediately after a 10-week instructional intervention, a replication of recent research. Additionally, the results of delayed assessment documented students' significant retention of that improvement five and a half months beyond the instructional intervention period. Essay enhancement served to highlight, via a coding procedure, students' successful and unsuccessful production of discourse-required target grammatical structures. The procedure converted students' written communicative output into enhanced input for inducing noticing of grammatical form and, through essay revision, establishing form-meaning connections leading to acquisition. With its optimal design characteristics supported by theoretical and empirical research, essay enhancement is a highly effective methodology that can be easily implemented as primary or supplementary English instruction for deaf students. The results of this study hold great promise for facilitating deaf students' English language and literacy development and have broad implications for second-language research, teaching, and learning.

  16. Glucocorticoids interact with noradrenergic activation at encoding to enhance long-term memory for emotional material in women.

    PubMed

    Segal, S K; Simon, R; McFarlin, S; Alkire, M; Desai, A; Cahill, L F

    2014-09-26

    Evidence from the animal literature suggests that post-training glucocorticoids (GCs) interact with noradrenergic activation at acquisition to enhance memory consolidation for emotional stimuli. While there is evidence that GCs enhance memory for emotional material in humans, the extent to which this depends on noradrenergic activation at encoding has not been explored. In this study, 20-mg hydrocortisone was administered to healthy young women (18-35 yrs old) in a double-blind fashion 10 min prior to viewing a series of emotional and neutral images. Saliva samples were taken at baseline, 10 min after drug or placebo administration, immediately after viewing the images, 10, 20, and 30 min after viewing the images. Participants returned 1 week later for a surprise recall test. Results suggest that, hydrocortisone administration resulted in emotional memory enhancement only in participants who displayed an increase in endogenous noradrenergic activation, measured via salivary alpha-amylase at encoding. These results support findings in the animal literature, and suggest that GC-induced memory enhancement relies on noradrenergic activation at encoding in women.

  17. Pulsatile delivery of a leucine supplement during long-term continuous enteral feeding enhances lean growth in term neonatal pigs

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Neonatal pigs are used as a model to study and optimize the clinical treatment of infants who are unable to maintain oral feeding. Using this model, we have previously shown that pulsatile administration of leucine during continuous feeding over 24 h via orogastric tube enhanced protein synthesis in...

  18. Staufen 2 Regulates mGluR Long-Term Depression and Map1b mRNA Distribution in Hippocampal Neurons

    ERIC Educational Resources Information Center

    Lebeau, Genevieve; Miller, Linda C.; Tartas, Maylis; McAdam, Robyn; Laplante, Isabel; Badeaux, Frederique; DesGroseillers, Luc; Sossin, Wayne S.; Lacaille, Jean-Claude

    2011-01-01

    The two members of the Staufen family of RNA-binding proteins, Stau1 and Stau2, are present in distinct ribonucleoprotein complexes and associate with different mRNAs. Stau1 is required for protein synthesis-dependent long-term potentiation (L-LTP) in hippocampal pyramidal cells. However, the role of Stau2 in synaptic plasticity remains…

  19. Kootenai River Wildlife Habitat Enhancement Project : Long-term Bighorn Sheep/Mule Deer Winter and Spring Habitat Improvement Project : Wildlife Mitigation Project, Libby Dam, Montana : Management Plan.

    SciTech Connect

    Yde, Chis

    1990-06-01

    The Libby hydroelectric project, located on the Kootenai River in northwestern Montana, resulted in several impacts to the wildlife communities which occupied the habitats inundated by Lake Koocanusa. Montana Department of Fish, Wildlife and Parks, in cooperation with the other management agencies, developed an impact assessment and a wildlife and wildlife habitat mitigation plan for the Libby hydroelectric facility. In response to the mitigation plan, Bonneville Power Administration funded a cooperative project between the Kootenai National Forest and Montana Department of Fish, Wildlife and Parks to develop a long-term habitat enhancement plan for the bighorn sheep and mule deer winter and spring ranges adjacent to Lake Koocanusa. The project goal is to rehabilitate 3372 acres of bighorn sheep and 16,321 acres of mule deer winter and spring ranges on Kootenai National Forest lands adjacent to Lake Koocanusa and to monitor and evaluate the effects of implementing this habitat enhancement work. 2 refs.

  20. Modeling long term Enhanced in situ Biodenitrification and induced heterogeneity in column experiments under different feeding strategies

    NASA Astrophysics Data System (ADS)

    Rodríguez-Escales, Paula; Folch, Albert; van Breukelen, Boris M.; Vidal-Gavilan, Georgina; Sanchez-Vila, Xavier

    2016-07-01

    Enhanced In situ Biodenitrification (EIB) is a capable technology for nitrate removal in subsurface water resources. Optimizing the performance of EIB implies devising an appropriate feeding strategy involving two design parameters: carbon injection frequency and C:N ratio of the organic substrate nitrate mixture. Here we model data on the spatial and temporal evolution of nitrate (up to 1.2 mM), organic carbon (ethanol), and biomass measured during a 342 day-long laboratory column experiment (published in Vidal-Gavilan et al., 2014). Effective porosity was 3% lower and dispersivity had a sevenfold increase at the end of the experiment as compared to those at the beginning. These changes in transport parameters were attributed to the development of a biofilm. A reactive transport model explored the EIB performance in response to daily and weekly feeding strategies. The latter resulted in significant temporal variation in nitrate and ethanol concentrations at the outlet of the column. On the contrary, a daily feeding strategy resulted in quite stable and low concentrations at the outlet and complete denitrification. At intermediate times (six months of experiment), it was possible to reduce the carbon load and consequently the C:N ratio (from 2.5 to 1), partly because biomass decay acted as endogenous carbon to respiration, keeping the denitrification rates, and partly due to the induced dispersivity caused by the well-developed biofilm, resulting in enhancement of mixing between the ethanol and nitrate and the corresponding improvement of denitrification rates. The inclusion of a dual-domain model improved the fit at the last days of the experiment as well as in the tracer test performed at day 342, demonstrating a potential transition to anomalous transport that may be caused by the development of biofilm. This modeling work is a step forward to devising optimal injection conditions and substrate rates to enhance EIB performance by minimizing the overall supply of

  1. Enhanced motor activity and brain dopamine turnover in mice during long-term nicotine administration in the drinking water.

    PubMed

    Gäddnäs, H; Pietilä, K; Piepponen, T P; Ahtee, L

    2001-12-01

    Nicotine was administered chronically to NMRI mice in their drinking water in gradually increasing concentrations to measure gross motor activity and brain nicotine concentrations over 24 h on the 50th day of nicotine administration. Also, the striatal postmortem tissue concentrations and accumbal extracellular concentrations of dopamine (DA) and its metabolites 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) were measured to study the role of dopaminergic systems in nicotine-induced hyperactivity in mice. The cerebral nicotine concentration was at its highest at the end of the dark period. The activity of nicotine-treated mice and their striatal DA metabolism were parallelly increased at 2 to 3 h after midnight and in the forenoon. Microdialysis experiments carried out in the forenoon showed that the extracellular levels of DA and DOPAC were elevated in the nucleus accumbens of these mice. Nicotine did not alter the circadian rhythmicity of activity in the mice. Rather, our findings suggest that the mice consume more nicotine when active and this might lead to enhanced release and metabolism of DA and further, to enhanced motor behavior. These findings support the suggestions that nicotine's effects on limbic and striatal DA are critical for its stimulating effects.

  2. Long term operation of continuous-flow system with enhanced biological phosphorus removal granules at different COD loading.

    PubMed

    Li, Dong; Lv, Yufeng; Zeng, Huiping; Zhang, Jie

    2016-09-01

    In this study, a continuous-flow system with enhanced biological phosphorus removal (EBPR) granules was operated at different COD concentrations (200, 300 and 400mgL(-)(1)) to investigate the effect of COD loading on this system. The results showed that when the COD concentration in influent was increased to 400mgL(-)(1), the anaerobic COD removal efficiency and total phosphorus removal efficiency reduced obviously and the settling ability of granules deteriorated due to the proliferation of filamentous bacteria. Moreover, high COD loading inhibited the EPS secretion and destroyed the stability of granules. Results of high-through pyrosequencing indicated that filamentous bacteria had a competitive advantage over polyphosphate-accumulating organisms (PAOs) at high COD loading. The performance of system, settling ability of granules and proportion of PAOs gradually recovered to the initial level after the COD concentration was reduced to 200mgL(-)(1) on day 81.

  3. Long-term forskolin stimulation induces AMPK activation and thereby enhances tight junction formation in human placental trophoblast BeWo cells.

    PubMed

    Egawa, M; Kamata, H; Kushiyama, A; Sakoda, H; Fujishiro, M; Horike, N; Yoneda, M; Nakatsu, Y; Ying, Guo; Jun, Zhang; Tsuchiya, Y; Takata, K; Kurihara, H; Asano, T

    2008-12-01

    BeWo cells, derived from human choriocarcinoma, have been known to respond to forskolin or cAMP analogues by differentiating into multinucleated cells- like syncytiotrophoblasts on the surfaces of chorionic villi of the human placenta. In this study, we demonstrated that long-term treatment with forskolin enhances the tight junction (TJ) formation in human placental BeWo cells. Interestingly, AMPK activation and phosphorylation of acetyl-CoA carboxylase (ACC), a molecule downstream from AMPK, were induced by long-term incubation (>12h) with forskolin, despite not being induced by acute stimulation with forskolin. In addition, co-incubation with an AMPK inhibitor, compound C, as well as overexpression of an AMPK dominant negative mutant inhibited forskolin-induced TJ formation. Thus, although the molecular mechanism underlying AMPK activation via the forskolin stimulation is unclear, the TJ formation induced by forskolin is likely to be mediated by the AMPK pathway. Taking into consideration that TJs are present in the normal human placenta, this mechanism may be important for forming the placental barrier system between the fetal and maternal circulations.

  4. Effects of long-term AA attendance and spirituality on the course of depressive symptoms in individuals with alcohol use disorder.

    PubMed

    Wilcox, Claire E; Pearson, Matthew R; Tonigan, J Scott

    2015-06-01

    Alcohol use disorder (AUD) is associated with depression. Although attendance at Alcoholics Anonymous (AA) meetings predicts reductions in drinking, results have been mixed about the salutary effects of AA on reducing depressive symptoms. In this single-group study, early AA affiliates (n = 253) were recruited, consented, and assessed at baseline, 3, 6, 9, 12, 18, and 24 months. Lagged growth models were used to investigate the predictive effect of AA attendance on depression, controlling for concurrent drinking and treatment attendance. Depression was measured using the Beck Depression Inventory (BDI) and was administered at baseline 3, 6, 12, 18, and 24 months. Additional predictors of depression tested included spiritual gains (Religious Background and Behavior questionnaire [RBB]) and completion of 12-step work (Alcoholics Anonymous Inventory [AAI]). Eighty-five percent of the original sample provided follow-up data at 24 months. Overall, depression decreased over the 24 month follow-up period. AA attendance predicted later reductions in depression (slope = -3.40, p = .01) even after controlling for concurrent drinking and formal treatment attendance. Finally, increased spiritual gains (RBB) also predicted later reductions in depression (slope = -0.10, p = .02) after controlling for concurrent drinking, treatment, and AA attendance. In summary, reductions in alcohol consumption partially explained decreases in depression in this sample of early AA affiliates, and other factors such as AA attendance and increased spiritual practices also accounted for reductions in depression beyond that explained by drinking. (PsycINFO Database Record

  5. Effects of Long-Term AA Attendance and Spirituality on the Course of Depressive Symptoms in Individuals with Alcohol Use Disorder

    PubMed Central

    Wilcox, Claire E.; Pearson, Matthew R.; Tonigan, J. Scott

    2016-01-01

    Alcohol use disorder (AUD) is associated with depression. Although attendance at Alcoholics Anonymous (AA) meetings predicts reductions in drinking, results have been mixed about the salutary effects of AA on reducing depressive symptoms. In this single-group study, early AA affiliates (n=253) were recruited, consented, and assessed at baseline, 3, 6, 9, 12, 18 and 24 months. Lagged growth models were used to investigate the predictive effect of AA attendance on depression, controlling for concurrent drinking and treatment attendance. Depression was measured using the Beck Depression Inventory (BDI) and was administered at baseline 3, 6, 12, 18 and 24 months. Additional predictors of depression tested included spiritual gains, [Religious Background and Behavior questionnaire (RBB)] and completion of 12-step work [(Alcoholics Anonymous Inventory (AAI)]. Eighty-five percent of the original sample provided follow-up data at 24 months. Overall, depression decreased over the 24 month follow-up period. AA attendance predicted later reductions in depression (slope=−3.40, p= 0.01) even after controlling for concurrent drinking and formal treatment attendance. Finally, increased spiritual gains (RBB) also predicted later reductions in depression (slope=−0.10, p=0.02) after controlling for concurrent drinking, treatment, and AA attendance. In sum, reductions in alcohol consumption partially explained decreases in depression in this sample of early AA affiliates, and other factors such as AA attendance and increased spiritual practices also accounted for reductions in depression beyond that explained by drinking. PMID:26076099

  6. Polyvinylidene fluoride/siloxane nanofibrous membranes for long-term continuous CO2 -capture with large absorption-flux enhancement.

    PubMed

    Lin, Yi-Feng; Wang, Chi-Sen; Ko, Chia-Chieh; Chen, Chien-Hua; Chang, Kai-Shiun; Tung, Kuo-Lun; Lee, Kueir-Rarn

    2014-02-01

    In a CO2 membrane contactor system, CO2 passes through a hydrophobic porous membrane in the gas phase to contact the amine absorbent in the liquid phase. Consequently, additional CO2 gas is absorbed by amine absorbents. This study examines highly porous polyvinylidene fluoride (PVDF)/siloxane nanofibrous layers that are modified with hydrophobic fluoroalkylsilane (FAS) functional groups and successfully coated onto a macroporous Al2 O3 membrane. The performance of these materials in a membrane contactor system for CO2 absorption is also investigated. Compared with pristine PVDF nanofibrous membranes, the PVDF/siloxane nanofibrous membranes exhibit greater solvent resistance and mechanical strength, making them more suitable for use in CO2 capture by the membrane contactor. The PVDF/siloxane nanofibrous layer in highly porous FAS-modified membranes can prevent the wetting of the membrane by the amine absorbent; this extends the periods of continuous CO2 absorption and results in a high CO2 absorption flux with a minimum of 500 % enhancement over that of the uncoated membranes. This study suggests the potential use of an FAS-modified PVDF/siloxane nanofibrous membrane in a membrane contactor system for CO2 absorption. The resulting hydrophobic membrane contactor also demonstrates the potential for large-scale CO2 absorption during post-combustion processes in power plants.

  7. Muscle tension induced after learning enhances long-term narrative and visual memory in healthy older adults.

    PubMed

    Nielson, Kristy A; Wulff, Laura L; Arentsen, Timothy J

    2014-03-01

    Arousing events are better remembered than mundane events. Indeed, manipulation of arousal, such as by muscle tension, can influence memory even when it occurs shortly after learning. Indeed, our founding study showed this approach can raise delayed memory performance in older adults to a level comparable to that of unaided young adults. Yet, systematic studies, especially those investigating different modalities or types of memory, have not been done. This study investigated the effects of a brief bout of isometric exercise via handgrip on narrative and visuospatial episodic memory in healthy elders. Forty-seven participants completed the Logical Memory subtest of the Wechsler Memory Scales III (LM) and the Benton Visual Retention Test (BVRT), followed alternately by no treatment and by moderately squeezing a sand-filled latex ball for 1-min (counterbalanced order and test forms). Isometric exercise significantly increased both positive and negative affect ratings. Retention was tested 2 weeks later. Delayed recall and recognition of LM was enhanced by arousal relative to control, as was recognition of the BVRT. The results extend past findings that muscle tension induced after learning modulates memory consolidation, extending findings in elders to suggest that a simple form of isometric exercise can have practical effects, such as aiding memory for stories and images.

  8. Parenteral adenoviral boost enhances BCG induced protection, but not long term survival in a murine model of bovine TB.

    PubMed

    Kaveh, Daryan A; Garcia-Pelayo, M Carmen; Webb, Paul R; Wooff, Esen E; Bachy, Véronique S; Hogarth, Philip J

    2016-07-25

    Boosting BCG using heterologous prime-boost represents a promising strategy for improved tuberculosis (TB) vaccines, and adenovirus (Ad) delivery is established as an efficacious boosting vehicle. Although studies demonstrate that intranasal administration of Ad boost to BCG offers optimal protection, this is not currently possible in cattle. Using Ad vaccine expressing the mycobacterial antigen TB10.4 (BCG/Ad-TB10.4), we demonstrate, parenteral boost of BCG immunised mice to induce specific CD8(+) IFN-γ producing T cells via synergistic priming of new epitopes. This induces significant improvement in pulmonary protection against Mycobacterium bovis over that provided by BCG when assessed in a standard 4week challenge model. However, in a stringent, year-long survival study, BCG/Ad-TB10.4 did not improve outcome over BCG, which we suggest may be due to the lack of additional memory cells (IL-2(+)) induced by boosting. These data indicate BCG-prime/parenteral-Ad-TB10.4-boost to be a promising candidate, but also highlight the need for further understanding of the mechanisms of T cell priming and associated memory using Ad delivery systems. That we were able to generate significant improvement in pulmonary protection above BCG with parenteral, rather than mucosal administration of boost vaccine is critical; suggesting that the generation of effective mucosal immunity is possible, without the risks and challenges of mucosal administration, but that further work to specifically enhance sustained protective immunity is required.

  9. 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.

  10. Long-term effects of sulphide on the enhanced biological removal of phosphorus: The symbiotic role of Thiothrix caldifontis.

    PubMed

    Rubio-Rincón, F J; Welles, L; Lopez-Vazquez, C M; Nierychlo, M; Abbas, B; Geleijnse, M; Nielsen, P H; van Loosdrecht, M C M; Brdjanovic, D

    2017-03-07

    Thiothrix caldifontis was the dominant microorganism (with an estimated bio-volume of 65 ± 3%) in a lab-scale enhanced biological phosphorus removal (EBPR) system containing 100 mg of sulphide per litre in the influent. After a gradual exposure to the presence of sulphide, the EBPR system initially dominated by Candidatus Accumulibacter phosphatis Clade I (98 ± 3% bio-volume) (a known polyphosphate accumulating organism, PAO) became enriched with T. caldifontis. Throughout the different operating conditions studied, practically 100% phosphate removal was always achieved. The gradual increase of the sulphide content in the medium (added to the anaerobic stage of the alternating anaerobic-aerobic sequencing batch reactor) and the adjustment of the aerobic hydraulic retention time played a major role in the enrichment of T. caldifontis. T. caldifontis exhibited a mixotrophic metabolism by storing carbon anaerobically as poly-β-hydroxy-alkanoates (PHA) and generating the required energy through the hydrolysis of polyphosphate. PHA was used in the aerobic period as carbon and energy source for growth, polyphosphate, and glycogen formation. Apparently, extra energy was obtained by the initial accumulation of sulphide as an intracellular sulphur, followed by its gradual oxidation to sulphate. The culture enriched with T. caldifontis was able to store approximately 100 mg P/g VSS. This research suggests that T. caldifontis could behave like PAO with a mixotrophic metabolism for phosphorus removal using an intracellular sulphur pool as energy source. These findings can be of major interest for the biological removal of phosphorus from wastewaters with low organic carbon concentrations containing reduced S-compounds like those (pre-)treated in anaerobic systems or from anaerobic sewers.

  11. Enhanced root exudation induces microbial feedbacks to N cycling in a pine forest under long-term CO2 fumigation.

    PubMed

    Phillips, Richard P; Finzi, Adrien C; Bernhardt, Emily S

    2011-02-01

    The degree to which rising atmospheric CO(2) will be offset by carbon (C) sequestration in forests depends in part on the capacity of trees and soil microbes to make physiological adjustments that can alleviate resource limitation. Here, we show for the first time that mature trees exposed to CO(2) enrichment increase the release of soluble C from roots to soil, and that such increases are coupled to the accelerated turnover of nitrogen (N) pools in the rhizosphere. Over the course of 3 years, we measured in situ rates of root exudation from 420 intact loblolly pine (Pinus taeda L.) roots. Trees fumigated with elevated CO(2) (200 p.p.m.v. over background) increased exudation rates (μg C cm(-1) root h(-1) ) by 55% during the primary growing season, leading to a 50% annual increase in dissolved organic inputs to fumigated forest soils. These increases in root-derived C were positively correlated with microbial release of extracellular enzymes involved in breakdown of organic N (R(2) = 0.66; P = 0.006) in the rhizosphere, indicating that exudation stimulated microbial activity and accelerated the rate of soil organic matter (SOM) turnover. In support of this conclusion, trees exposed to both elevated CO(2) and N fertilization did not increase exudation rates and had reduced enzyme activities in the rhizosphere. Collectively, our results provide field-based empirical support suggesting that sustained growth responses of forests to elevated CO(2) in low fertility soils are maintained by enhanced rates of microbial activity and N cycling fuelled by inputs of root-derived C. To the extent that increases in exudation also stimulate SOM decomposition, such changes may prevent soil C accumulation in forest ecosystems.

  12. Novel agonists for serotonin 5-HT7 receptors reverse metabotropic glutamate receptor-mediated long-term depression in the hippocampus of wild-type and Fmr1 KO mice, a model of Fragile X Syndrome.

    PubMed

    Costa, Lara; Sardone, Lara M; Lacivita, Enza; Leopoldo, Marcello; Ciranna, Lucia

    2015-01-01

    Serotonin 5-HT7 receptors are expressed in the hippocampus and modulate the excitability of hippocampal neurons. We have previously shown that 5-HT7 receptors modulate glutamate-mediated hippocampal synaptic transmission and long-term synaptic plasticity. In particular, we have shown that activation of 5-HT7 receptors reversed metabotropic glutamate receptor-mediated long-term depression (mGluR-LTD) in wild-type (wt) and in Fmr1 KO mice, a mouse model of Fragile X Syndrome in which mGluR-LTD is abnormally enhanced, suggesting that 5-HT7 receptor agonists might be envisaged as a novel therapeutic strategy for Fragile X Syndrome. In this perspective, we have characterized the basic in vitro pharmacokinetic properties of novel molecules with high binding affinity and selectivity for 5-HT7 receptors and we have tested their effects on synaptic plasticity using patch clamp on acute hippocampal slices. Here we show that LP-211, a high affinity selective agonist of 5-HT7 receptors, reverses mGluR-LTD in wt and Fmr1 KO mice, correcting a synaptic malfunction in the mouse model of Fragile X Syndrome. Among novel putative agonists of 5-HT7 receptors, the compound BA-10 displayed improved affinity and selectivity for 5-HT7 receptors and improved in vitro pharmacokinetic properties with respect to LP-211. BA-10 significantly reversed mGluR-LTD in the CA3-CA1 synapse in wt and Fmr1KO mice, indicating that BA-10 behaved as a highly effective agonist of 5-HT7 receptors and reduced exaggerated mGluR-LTD in a mouse model of Fragile X Syndrome. On the other side, the compounds RA-7 and PM-20, respectively arising from in vivo metabolism of LP-211 and BA-10, had no effect on mGluR-LTD thus did not behave as agonists of 5-HT7 receptors in our conditions. The present results provide information about the structure-activity relationship of novel 5-HT7 receptor agonists and indicate that LP-211 and BA-10 might be used as novel pharmacological tools for the therapy of Fragile X Syndrome.

  13. Novel agonists for serotonin 5-HT7 receptors reverse metabotropic glutamate receptor-mediated long-term depression in the hippocampus of wild-type and Fmr1 KO mice, a model of Fragile X Syndrome

    PubMed Central

    Costa, Lara; Sardone, Lara M.; Lacivita, Enza; Leopoldo, Marcello; Ciranna, Lucia

    2015-01-01

    Serotonin 5-HT7 receptors are expressed in the hippocampus and modulate the excitability of hippocampal neurons. We have previously shown that 5-HT7 receptors modulate glutamate-mediated hippocampal synaptic transmission and long-term synaptic plasticity. In particular, we have shown that activation of 5-HT7 receptors reversed metabotropic glutamate receptor-mediated long-term depression (mGluR-LTD) in wild-type (wt) and in Fmr1 KO mice, a mouse model of Fragile X Syndrome in which mGluR-LTD is abnormally enhanced, suggesting that 5-HT7 receptor agonists might be envisaged as a novel therapeutic strategy for Fragile X Syndrome. In this perspective, we have characterized the basic in vitro pharmacokinetic properties of novel molecules with high binding affinity and selectivity for 5-HT7 receptors and we have tested their effects on synaptic plasticity using patch clamp on acute hippocampal slices. Here we show that LP-211, a high affinity selective agonist of 5-HT7 receptors, reverses mGluR-LTD in wt and Fmr1 KO mice, correcting a synaptic malfunction in the mouse model of Fragile X Syndrome. Among novel putative agonists of 5-HT7 receptors, the compound BA-10 displayed improved affinity and selectivity for 5-HT7 receptors and improved in vitro pharmacokinetic properties with respect to LP-211. BA-10 significantly reversed mGluR-LTD in the CA3-CA1 synapse in wt and Fmr1KO mice, indicating that BA-10 behaved as a highly effective agonist of 5-HT7 receptors and reduced exaggerated mGluR-LTD in a mouse model of Fragile X Syndrome. On the other side, the compounds RA-7 and PM-20, respectively arising from in vivo metabolism of LP-211 and BA-10, had no effect on mGluR-LTD thus did not behave as agonists of 5-HT7 receptors in our conditions. The present results provide information about the structure-activity relationship of novel 5-HT7 receptor agonists and indicate that LP-211 and BA-10 might be used as novel pharmacological tools for the therapy of Fragile X Syndrome

  14. A randomized controlled trial of combined exercise and psycho-education for low-SES women: short- and long-term outcomes in the reduction of stress and depressive symptoms.

    PubMed

    van der Waerden, Judith E B; Hoefnagels, Cees; Hosman, Clemens M H; Souren, Pierre M; Jansen, Maria W J

    2013-08-01

    Exercise may have both a preventive and a therapeutic impact on mental health problems. The Exercise without Worries intervention aims to reduce stress and depressive symptoms in low-SES women by means of a group-based program combining physical exercise and psycho-education. Between September 2005 and May 2008, 161 Dutch low-SES women with elevated stress or depressive symptom levels were randomly assigned to the combined exercise/psycho-education intervention (EP), exercise only (E) or a waiting list control condition (WLC). The E condition provided low to moderate intensity stretching, strength, flexibility, and body focused training as well as relaxation, while the EP program integrated the exercise with cognitive-behavioral techniques. Depressive symptoms (CES-D) and perceived stress (PSS) were measured before and immediately after the intervention and at 2, 6 and 12 month follow-up. Multilevel linear mixed-effects models revealed no differential patterns in reduction of CES-D or PSS scores between the EP, E and WLC groups on the short (post-test and 2 month follow-up) or long term (6 and 12 months follow-up). Depressive symptom outcomes were moderated by initial depressive symptom scores: women from the EP and E groups with fewer initial symptoms benefited from participation on the short term. Further, women in the EP and E groups with the lowest educational level reported more stress reduction at post-test than women with higher educational levels. In the overall target population of low-SES women, no indications were found that the Exercise without Worries course reduced depressive symptom and stress levels on the short or long term. The findings do suggest, however, that exercise alone or in combination with psycho-education may be a viable prevention option for certain groups of disadvantaged women. Especially those low-SES women with less severe initial problems or those with low educational attainment should be targeted for future depression prevention

  15. [The effect of long-term external ionizing radiation on the functional activity of rat thyroid under enhanced potassium iodide consumption].

    PubMed

    Lupachik, S V; Nadol'nik, L I

    2008-01-01

    The study was devoted to the effect of long-term (20 days) external ionizing radiation at a dose of 0.5 Gy on the iodide metabolism in the rat thyroid under supplementation of high iodine doses (10 daily KI doses). It was found that the potassium iodide administration partially prevented the effects of a post radiation decrease of serum thyroid hormone levels (the level of T4 was normal and that of T3 was 77.4% of the controls). After the supplementation of 10 daily iodide doses, the rat thyroid tissue showed the most pronounced increase in the levels of total, free and protein-bound iodide compared to the groups of animals consuming normal and elevated KI doses. Pronounced inhibition of thyroid peroxidase activity (3.1-fold) was noted in the same group. The data obtained indicate a radiation-induced activation of iodide uptake during its enhanced supplementation and disturbed iodide enzymatic oxidation and organification.

  16. Response of aboveground carbon balance to long-term, experimental enhancements in precipitation seasonality is contingent on plant community type in cold-desert rangelands

    USGS Publications Warehouse

    McAbee, Kathryn; Reinhardt, Keith; Germino, Matthew; Bosworth, Andrew

    2017-01-01

    Semi-arid rangelands are important carbon (C) pools at global scales. However, the degree of net C storage or release in water-limited systems is a function of precipitation amount and timing, as well as plant community composition. In northern latitudes of western North America, C storage in cold-desert ecosystems could increase with boosts in wintertime precipitation, in which climate models predict, due to increases in wintertime soil water storage that enhance summertime productivity. However, there are few long-term, manipulative field-based studies investigating how rangelands will respond to altered precipitation amount or timing. We measured aboveground C pools and fluxes at leaf, soil, and ecosystem scales over a single growing season in plots that had 200 mm of supplemental precipitation added in either winter or summer for the past 21 years, in shrub- and exotic-bunchgrass-dominated garden plots. At our cold-desert site (298 mm precipitation during the study year), we hypothesized that increased winter precipitation would stimulate the aboveground C uptake and storage relative to ambient conditions, especially in plots containing shrubs. Our hypotheses were generally supported: ecosystem C uptake and long-term biomass accumulation were greater in winter- and summer-irrigated plots compared to control plots in both vegetation communities. However, substantial increases in the aboveground biomass occurred only in winter-irrigated plots that contained shrubs. Our findings suggest that increases in winter precipitation will enhance C storage of this widespread ecosystem, and moreso in shrub- compared to grass-dominated communities.

  17. Long-term enhancement of REM sleep by the pituitary adenylyl cyclase-activating polypeptide (PACAP) in the pontine reticular formation of the rat.

    PubMed

    Ahnaou, A; Basille, M; Gonzalez, B; Vaudry, H; Hamon, M; Adrien, J; Bourgin, P

    1999-11-01

    In rats, rapid eye movement (REM) sleep can be elicited by microinjection of vasoactive intestinal polypeptide (VIP) into the oral pontine reticular nucleus (PnO). In the present study, we investigated whether this area could also be a REM-promoting target for a peptide closely related to VIP: the pituitary adenylyl cyclase-activating polypeptide (PACAP). When administered into the posterior part of the PnO, but not in nearby areas, of freely moving chronically implanted rats, PACAP-27 and PACAP-38 (0.3 and 3 pmol) induced a marked enhancement (60-85% over baseline) of REM sleep for 8 h that could be prevented by prior infusion of the antagonist PACAP-(6-27) (3 pmol) into the same site. Moreover, injections of PACAP into the centre of the posterior PnO resulted in REM sleep enhancement which could last for up to 11 consecutive days. Quantitative autoradiography using [125I]PACAP-27 revealed the presence in the PnO of specific binding sites with high affinity for PACAP-27 and PACAP-38 (IC50 = 2.4 and 3.2 nM, respectively), but very low affinity for VIP (IC50 > 1 microM). These data suggest that PACAP within the PnO may play a key role in REM sleep regulation, and provide evidence for long-term (several days) mechanisms involved in such a control. PAC1 receptors which have a much higher affinity for PACAP than for VIP might mediate this long-term action of PACAP on REM sleep.

  18. Response of aboveground carbon balance to long-term, experimental enhancements in precipitation seasonality is contingent on plant community type in cold-desert rangelands.

    PubMed

    McAbee, Kathryn; Reinhardt, Keith; Germino, Matthew J; Bosworth, Andrew

    2017-03-01

    Semi-arid rangelands are important carbon (C) pools at global scales. However, the degree of net C storage or release in water-limited systems is a function of precipitation amount and timing, as well as plant community composition. In northern latitudes of western North America, C storage in cold-desert ecosystems could increase with boosts in wintertime precipitation, in which climate models predict, due to increases in wintertime soil water storage that enhance summertime productivity. However, there are few long-term, manipulative field-based studies investigating how rangelands will respond to altered precipitation amount or timing. We measured aboveground C pools and fluxes at leaf, soil, and ecosystem scales over a single growing season in plots that had 200 mm of supplemental precipitation added in either winter or summer for the past 21 years, in shrub- and exotic-bunchgrass-dominated garden plots. At our cold-desert site (298 mm precipitation during the study year), we hypothesized that increased winter precipitation would stimulate the aboveground C uptake and storage relative to ambient conditions, especially in plots containing shrubs. Our hypotheses were generally supported: ecosystem C uptake and long-term biomass accumulation were greater in winter- and summer-irrigated plots compared to control plots in both vegetation communities. However, substantial increases in the aboveground biomass occurred only in winter-irrigated plots that contained shrubs. Our findings suggest that increases in winter precipitation will enhance C storage of this widespread ecosystem, and moreso in shrub- compared to grass-dominated communities.

  19. Enhancement of Glutamate Release by l-Fucose Changes Effects of Glutamate Receptor Antagonists on Long-Term Potentiation in the Rat Hippocampus

    PubMed Central

    Matthies, Henry; Schroeder, Helmut; Smalla, Karl-Heinz; Krug, Manfred

    2000-01-01

    In previous studies l-fucose has been shown to facilitate long-term memory formation and to enhance and prolong long-term potentiation (LTP). To search for possible presynaptic or postsynaptic mechanisms that are affected by l-fucose, we examined the effect of l-fucose on (1) inhibition of LTP induction via glutamate receptors by antagonists, (2) paired-pulse facilitation, and (3) presynaptic transmitter release. Coapplication of 0.2 mm l-fucose with the competitive N-methyl-d-aspartate (NMDA) receptor antagonist, d-2-amino-5-phosphonovalerate (AP5), or coapplication of 0.2 mml-fucose in the presence of an inhibitor for class I/II metabotropic glutamate receptors, (S)-α-methyl-4-carboxyphenylglycine (MCPG), reversed LTP blockade in the CA1-region of hippocampal slices. In contrast, l-fucose had no effect on the LTP blockade by the noncompetitive NMDA ion-channel blocker (5R,10S)-(+)-5-Methyl-10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5, 10-imine hydrogen maleate (MK-801). Paired-pulse facilitation, which is a primarily presynaptic phenomenon of short-term plasticity, was decreased in the presence of 0.2 mm l-fucose. Furthermore, l-fucose enhanced the K+-stimulated release of [3H]-d-aspartate from preloaded hippocampal slices in a concentration-dependent manner. These observations demonstrate an influence of l-fucose on transmitter release that in turn can increase transmitter availability at postsynaptic glutamate receptors. This effect of l-fucose may contribute to the LTP facilitation seen in vitro and in vivo as well as to improvement in memory formation. PMID:10940323

  20. The Clinical Research Center for Depression Study: Baseline Characteristics of a Korean Long-Term Hospital-Based Observational Collaborative Prospective Cohort Study

    PubMed Central

    Kim, Tae-Suk; Jeong, Seung Hee; Kim, Jung-Bum; Lee, Min-Soo; Kim, Jae-Min; Yim, Hyeon-Woo

    2011-01-01

    Objective The Clinical Research Center for Depression (CRESCEND) study is a 9-year observational collaborative prospective cohort study for the clinical outcomes in participants with depressive disorders in Korea. In this study, we examined the baseline characteristics of the depressive participants as the hospital-based cohort. Methods Participants were assessed using various instruments including the Clinical Global Impression scale, 17-item Hamilton Depression Rating Scale (HDRS-17), Hamilton Anxiety Rating Scale, Brief Psychiatric Rating Scale, Social and Occupational Functioning Assessment Scale, Beck Depression Inventory-Second Edition, Scale for Suicide Ideation, and World Health Organization Quality of Life assessment instruments-abbreviated version. Also, personal histories of medical and psychiatric illnesses and the range of socio-epidemiologic and clinical data were collected from each participant. Results One thousand one hundred eighty three participants were recruited from 18 hospitals. The mean age of the participants was 47.9±15.9 year-old, 74.4% were female, 82.9% had been diagnosed of major depressive disorder, 40.9% were experiencing their first depressive episode, and 21.4% had a past history of suicide attempts. The majority (85.3%) of the participants were moderately to severely ill. The average HDRS-17 was 19.8±6.1. Significant gender differences at baseline were shown in age, education, marriage, employment, religion, and first depressive episode. Conclusion The baseline findings in the CRESCEND study showed some different characteristics of depression in Korea, suggesting a possibility of ethnic and cultural factors in depression. PMID:21519530

  1. Perceptions of control and long-term recovery from rape.

    PubMed

    Regehr, C; Cadell, S; Jansen, K

    1999-01-01

    The relationship between perceptions of control and symptoms of both long-term depression and post-traumatic stress was examined. Enduring beliefs of personal competence and control were found to be associated with lower rates of depression and stress and to be stronger predictors of long-term recovery than were rape-specific attributions. Implications for clinical practice are discussed.

  2. Long-Term Effects of the Booster-Enhanced READY-Girls Preconception Counseling Program on Intentions and Behaviors for Family Planning in Teens With Diabetes

    PubMed Central

    Charron-Prochownik, Denise; Sereika, Susan M.; Becker, Dorothy; White, Neil H.; Schmitt, Patricia; Powell, A. Blair; Diaz, Ana Maria; Jones, Jacquelyn; Herman, William H.; Rodgers Fischl, Andrea F.; McEwen, Laura; DiNardo, Monica; Guo, Feng; Downs, Julie

    2013-01-01

    OBJECTIVE To examine 12-month effects of a booster-enhanced preconception counseling (PC) program (READY-Girls) on family planning for teen girls with type 1 and type 2 diabetes. RESEARCH DESIGN AND METHODS Participants 13–19 years of age (n = 109) were randomized to a standard care control group (CG) or intervention group (IG) that received PC over three consecutive clinic visits. Prepost data were collected at baseline, 3- and 6-month booster sessions, and a 12-month follow-up visit. RESULTS Mean age was 15.8 years; 9 (8%) subjects had type 2 diabetes; and 18 (17%) subjects were African American. At baseline, 20% (n = 22 of 109) had been sexually active, and of these, 50% (n = 11) had at least one episode of unprotected sex. Over time, IG participants retained greater PC knowledge (F[6, 541] = 4.05, P = 0.0005) and stronger intentions regarding PC (significant group-by-time effects) especially after boosters. IG participants had greater intentions to discuss PC (F[6, 82.4] = 2.56, P = 0.0254) and BC (F[6, 534] = 3.40, P = 0.0027) with health care providers (HCPs) and seek PC when planning a pregnancy (F[6, 534] = 2.58, P = 0.0180). Although not significant, IG participants, compared with CG, showed a consistent trend toward lower rates of overall sexual activity over time: less sexual debut (35 vs. 41%) and higher rates of abstinence (44 vs. 32%). No pregnancies were reported in either group throughout the study. CONCLUSIONS READY-Girls appeared to have long-term sustaining effects on PC knowledge, beliefs, and intentions to initiate discussion with HCPs that could improve reproductive health behaviors and outcomes. Strong boosters and providing PC at each clinic visit could play important roles in sustaining long-term effects. PMID:24130343

  3. Enhancement of long-term memory retention by Colostrinin in one-day-old chicks trained on a weak passive avoidance learning paradigm.

    PubMed

    Stewart, Michael G; Banks, Duncan

    2006-07-01

    Colostrinin (CLN) is a biologically active proline-rich polypeptide which has therapeutic potential for the alleviation of memory deficits in age-related dementias in a number of human conditions, particularly Alzheimer's disease. To examine the efficacy of CLN in other species, day-old domestic chicks were used as a model system to study its effects on retention of memory for a single one-trial learning paradigm--avoidance of a bitter-tasting substance (methylanthranilate, MeA). Birds were presented with a bead coated with either a dilute (10%) solution of MeA or a bead coated with 100% MeA. Those trained on 100% MeA avoided pecking at a similar but dry bead 24 h later, thereby demonstrating long-term memory whereas chicks trained on the 10% solution pecked the bead at 24 h, indicating lack of long term memory for the task. However, when CLN was injected (i.c.) into a region known to be important in memory formation, the mesopallium intermediomediale (IMM), prior to training with 10% MeA, chicks exhibited strong memory retention at 24 h, similar to those trained on 100% MeA. Control chicks trained on 10% MeA but injected i.c. with a 10% saline solution did not show improvement in memory retention. Intraperitoneal (i.p.) injections of CLN were as effective as the i.c. route. These data extend the known efficacy of CLN from mammals demonstrating its widespread efficacy as a cognitive enhancer.

  4. Enhancement of GluN2B Subunit-Containing NMDA Receptor Underlies Serotonergic Regulation of Long-Term Potentiation after Critical Period in the Rat Visual Cortex

    PubMed Central

    Joo, Kayoung; Rhie, Duck-Joo

    2015-01-01

    Serotonin [5-hydroxytryptamine (5-HT)] regulates synaptic plasticity in the visual cortex. Although the effects of 5-HT on plasticity showed huge diversity depending on the ages of animals and species, it has been unclear how 5-HT can show such diverse effects. In the rat visual cortex, 5-HT suppressed long-term potentiation (LTP) at 5 weeks but enhanced LTP at 8 weeks. We speculated that this difference may originate from differential regulation of neurotransmission by 5-HT between the age groups. Thus, we investigated the effects of 5-HT on apha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR)-, γ-aminobutyric acid receptor type A (GABAAR)-, and N-methyl-D-aspartic acid receptor (NMDAR)-mediated neurotransmissions and their involvement in the differential regulation of plasticity between 5 and 8 weeks. AMPAR-mediated currents were not affected by 5-HT at both 5 and 8 weeks. GABAAR-mediated currents were enhanced by 5-HT at both age groups. However, 5-HT enhanced NMDAR-mediated currents only at 8 weeks. The enhancement of NMDAR-mediated currents appeared to be mediated by the enhanced function of GluN2B subunit-containing NMDAR. The enhanced GABAAR- and NMDAR-mediated neurotransmissions were responsible for the suppression of LTP at 5 weeks and the facilitation of LTP at 8 weeks, respectively. These results indicate that the effects of 5-HT on neurotransmission change with development, and the changes may underlie the differential regulation of synaptic plasticity between different age groups. Thus, the developmental changes in 5-HT function should be carefully considered while investigating the 5-HT-mediated metaplastic control of the cortical network. PMID:26557019

  5. Long-term cost-effectiveness of collaborative care (vs usual care) for people with depression and comorbid diabetes or cardiovascular disease: a Markov model informed by the COINCIDE randomised controlled trial

    PubMed Central

    Camacho, Elizabeth M; Ntais, Dionysios; Coventry, Peter; Bower, Peter; Lovell, Karina; Chew-Graham, Carolyn; Baguley, Clare; Gask, Linda; Dickens, Chris; Davies, Linda M

    2016-01-01

    Objectives To evaluate the long-term cost-effectiveness of collaborative care (vs usual care) for treating depression in patients with diabetes and/or coronary heart disease (CHD). Setting 36 primary care general practices in North West England. Participants 387 participants completed baseline assessment (collaborative care: 191; usual care: 196) and full or partial 4-month follow-up data were captured for 350 (collaborative care: 170; usual care: 180). 62% of participants were male, 14% were non-white. Participants were aged ≥18 years, listed on a Quality and Outcomes Framework register for CHD and/or type 1 or 2 diabetes mellitus, with persistent depressive symptoms. Patients with psychosis or type I/II bipolar disorder, actively suicidal, in receipt of services for substance misuse, or already in receipt of psychological therapy for depression were excluded. Intervention Collaborative care consisted of evidence-based low-intensity psychological treatments, delivered over 3 months and case management by a practice nurse and a Psychological Well Being Practitioner. Outcome measures As planned, the primary measure of cost-effectiveness was the incremental cost-effectiveness ratio (cost per quality-adjusted life year (QALY)). A Markov model was constructed to extrapolate the trial results from short-term to long-term (24 months). Results The mean cost per participant of collaborative care was £317 (95% CI 284 to 350). Over 24 months, it was estimated that collaborative care was associated with greater healthcare usage costs (net cost £674 (95% CI −30 953 to 38 853)) and QALYs (net QALY gain 0.04 (95% CI −0.46 to 0.54)) than usual care, resulting in a cost per QALY gained of £16 123, and a likelihood of being cost-effective of 0.54 (willingness to pay threshold of £20 000). Conclusions Collaborative care is a potentially cost-effective long-term treatment for depression in patients with comorbid physical and mental illness. The estimated

  6. Child protection and adult depression: evaluating the long-term consequences of evacuating children to foster care during World War II.

    PubMed

    Santavirta, Nina; Santavirta, Torsten

    2014-03-01

    This paper combined data collected from war time government records with survey data including background characteristics, such as factors that affected eligibility, to examine the adult depression outcomes of individuals who were evacuated from Finland to temporary foster care in Sweden during World War II. Using war time government records and survey data for a random sample of 723 exposed individuals and 1321 matched unexposed individuals, the authors conducted least squares adjusted means comparison to examine the association between evacuation and adult depression (Beck Depression Inventory). The random sample was representative for the whole population of evacuees who returned to their biological families after World War II. The authors found no statistically significant difference in depressive symptoms during late adulthood between the two groups; for example, the exposed group had a 0.41 percentage points lower average Beck Depression Inventory score than the unexposed group (p = 0.907). This study provides no support for family disruption during early childhood because of the onset of sudden shocks elevating depressive symptoms during late adulthood.

  7. Oral health-related quality of life and depression/anxiety in long-term recurrence-free patients after treatment for advanced oral squamous cell cancer.

    PubMed

    Hassel, Alexander J; Danner, Daniel; Freier, Kolja; Hofele, Christof; Becker-Bikowski, Kirsten; Engel, Michael

    2012-06-01

    This report focuses on the association between oral health-related quality of life (OHRQoL) and depression/anxiety of a homogeneous group of cancer patients who were recurrence-free for 8 years after treatment for advanced oral squamous cell. Participants were 24 patients (mean age 55 years, 75% men) treated with neoadjuvant concurrent radiochemotherapy followed by surgery with a mean recurrence-free period of 95 months (from 39 to 164 months). The OHRQoL (OHIP) and the anxiety/depression (HADS) were assessed twice (1 year between t1 and t2). OHRQoL was impaired in this group (mean OHIP score 65 units). In cross-lagged correlation analysis, the correlation between OHRQoL to t1 and depression to t2 was significant and greater than the non-significant correlation for depression to t1 and OHRQoL to t2 indicating that OHRQoL predicts depression better than vice versa. However, the difference in the correlation coefficients was not significant (ZPF-test). The same was true for OHRQoL and anxiety. The OHRQoL measured with the OHIP was impaired in comparison to the normal population. In the limitations of the study design and bearing the small sample size in mind, the results give evidence that OHRQoL predicts psychological outcomes, namely depression and anxiety, better than vice versa.

  8. Long-term bicycle riding ameliorates the depression of the patients undergoing hemodialysis by affecting the levels of interleukin-6 and interleukin-18

    PubMed Central

    Zhao, Chunhui; Ma, Hui; Yang, Lei; Xiao, Yong

    2017-01-01

    Purpose Hemodialysis patients with depression have a higher risk of death and hospitalization. Although there is pharmacological management for the depression of hemodialysis patients, the adverse effect of the drug limits the use. The nonpharmacological way, bicycle riding, may be an effective way for the therapy of the depression in hemodialysis patients. However, the underlying mechanism of this relationship is still not fully explained, while interleukin-6 (IL-6) and interleukin-18 (IL-18) are associated with depression and exercise. Thus, the effects of bicycle riding on the levels of the interleukin were explored. Participants and methods One hundred and eighty-nine patients with chronic hemodialysis were selected and randomly assigned to three groups of medicine (MG, received 20-mg escitalopram daily), medicine and aerobic exercise (MAG, received 20-mg escitalopram daily and bicycle riding six times weekly), and only aerobic exercise (AG, received 20-mg placebo daily and bicycle riding six times weekly). The whole experiment lasted for 18 weeks. The quality of life (36-Item Short Form Health Survey) and depression severity according to criteria in the Diagnostic and Statistical Manual of Mental Disorders, fourth edition [DSM-IV] were measured before and at the end of this study. The serum levels of IL-6 and IL-18 were measured by an enzyme-linked immunosorbent assay kit. Results The quality of life was improved and depression severity was reduced significantly in the MAG and AG groups when compared with the MG group (P<0.05). Serum levels of IL-6 and IL-18 were the highest in the MG group, moderate in the MAG group and the lowest in AG group. On the other hand, the serum levels of IL-6 and IL-18 were closely associated with depression scores (P<0.05). Conclusion Aerobic exercise improves the quality of life and ameliorates the depression severity of the patients undergoing hemodialysis by affecting the levels of IL-6 and IL-18. Bicycle riding is a potential

  9. Caffeine suppresses exercise-enhanced long-term and location memory in middle-aged rats: Involvement of hippocampal Akt and CREB signaling.

    PubMed

    Cechella, José L; Leite, Marlon R; da Rocha, Juliana T; Dobrachinski, Fernando; Gai, Bibiana M; Soares, Félix A A; Bresciani, Guilherme; Royes, Luiz F F; Zeni, Gilson

    2014-11-05

    The cognitive function decline is closely related with brain changes generated by age. The ability of caffeine and exercise to prevent memory impairment has been reported in animal models and humans. The purpose of the present study was to investigate whether swimming exercise and caffeine administration enhance memory in middle-aged Wistar rats. Male Wistar rats (18months) received caffeine at a dose of 30mg/kg, 5days per week by a period of 4weeks. Animals were subjected to swimming training with a workload (3% of body weight, 20min per day for 4weeks). After 4weeks, the object recognition test (ORT) and the object location test (OLT) were performed. The results of this study demonstrated that caffeine suppressed exercise-enhanced long-term (ORT) and spatial (OLT) memory in middle-aged and this effect may be related to a decrease in hippocampal p-CREB signaling. This study also provided evidence that the effects of this protocol on memory were not accompanied by alterations in the levels of activated Akt. The [(3)H] glutamate uptake was reduced in hippocampus of rats administered with caffeine and submitted to swimming protocol.

  10. The n-butanolic extract of Opuntia ficus-indica var. saboten enhances long-term memory in the passive avoidance task in mice.

    PubMed

    Kim, Jong Min; Kim, Dong Hyun; Park, Se Jin; Park, Dong Hyun; Jung, Seo Yun; Kim, Hyoung Ja; Lee, Yong Sup; Jin, Changbae; Ryu, Jong Hoon

    2010-08-16

    Opuntia ficus-indica var. saboten Makino (Cactaceae) is used to treat burns, edema, dyspepsia, and asthma in traditional medicine. The present study investigated the beneficial effects of the n-butanolic extract of O. ficus-indica var. saboten (BOF) on memory performance in mice and attempts to uncover the mechanisms underlying its action. Memory performance was assessed with the passive avoidance task, and western blotting and immunohistochemistry were used to measure changes in protein expression and cell survival. After the oral administration of BOF for 7 days, the latency time in the passive avoidance task was significantly increased relative to vehicle-treated controls (P<0.05). Western blotting revealed that the expression levels of brain-derived neurotrophic factor (BDNF), phosphorylated cAMP response element binding-protein (pCREB), and phosphorylated extracellular signal-regulated kinase (pERK) 1/2 were significantly increased in hippocampal tissue after 7 days of BOF administration (P<0.05). Doublecortin and 5-bromo-2-deoxyuridine immunostaining also revealed that BOF significantly enhanced the survival of immature neurons, but did not affect neuronal cell proliferation in the subgranular zone of the hippocampal dentate gyrus. These results suggest that the subchronic administration of BOF enhances long-term memory, and that this effect is partially mediated by ERK-CREB-BDNF signaling and the survival of immature neurons.

  11. Web-Enhanced Instruction and Learning: Findings of a Short- and Long-Term Impact Study and Teacher Use of NASA Web Resources

    NASA Technical Reports Server (NTRS)

    McCarthy, Marianne C.; Grabowski, Barbara L.; Koszalka, Tiffany

    2003-01-01

    Over a three-year period, researchers and educators from the Pennsylvania State University (PSU), University Park, Pennsylvania, and the NASA Dryden Flight Research Center (DFRC), Edwards, California, worked together to analyze, develop, implement and evaluate materials and tools that enable teachers to use NASA Web resources effectively for teaching science, mathematics, technology and geography. Two conference publications and one technical paper have already been published as part of this educational research series on Web-based instruction and learning. This technical paper, Web-Enhanced Instruction and Learning: Findings of a Short- and Long-Term Impact Study, is the culminating report in this educational research series and is based on the final report submitted to NASA. This report describes the broad spectrum of data gathered from teachers about their experiences using NASA Web resources in the classroom. It also describes participating teachers responses and feedback about the use of the NASA Web-Enhanced Learning Environment Strategies reflection tool on their teaching practices. The reflection tool was designed to help teachers merge the vast array of NASA resources with the best teaching methods, taking into consideration grade levels, subject areas and teaching preferences. The teachers described their attitudes toward technology and innovation in the classroom and their experiences and perceptions as they attempted to integrate Web resources into science, mathematics, technology and geography instruction.

  12. Dose-dependent effect of donepezil administration on long-term enhancement of visually evoked potentials and cholinergic receptor overexpression in rat visual cortex.

    PubMed

    Chamoun, Mira; Groleau, Marianne; Bhat, Menakshi; Vaucher, Elvire

    2016-09-01

    Stimulation of the cholinergic system tightly coupled with periods of visual stimulation boosts the processing of specific visual stimuli via muscarinic and nicotinic receptors in terms of intensity, priority and long-term effect. However, it is not known whether more diffuse pharmacological stimulation with donepezil, a cholinesterase inhibitor, is an efficient tool for enhancing visual processing and perception. The goal of the present study was to potentiate cholinergic transmission with donepezil treatment (0.5 and 1mg/kg) during a 2-week visual training to examine the effect on visually evoked potentials and to profile the expression of cholinergic receptor subtypes. The visual training was performed daily, 10min a day, for 2weeks. One week after the last training session, visual evoked potentials were recorded, or the mRNA expression level of muscarinic (M1-5) and nicotinic (α/β) receptors subunits was determined by quantitative RT-PCR. The visual stimulation coupled with any of the two doses of donepezil produced significant amplitude enhancement of cortical evoked potentials compared to pre-training values. The enhancement induced by the 1mg/kg dose of donepezil was spread to neighboring spatial frequencies, suggesting a better sensitivity near the visual detection threshold. The M3, M4, M5 and α7 receptors mRNA were upregulated in the visual cortex for the higher dose of donepezil but not the lower one, and the receptors expression was stable in the somatosensory (non-visual control) cortex. Therefore, higher levels of acetylcholine within the cortex sustain the increased intensity of the cortical response and trigger the upregulation of cholinergic receptors.

  13. Allosteric Modulation of Related Ligand-Gated Ion Channels Synergistically Induces Long-Term Potentiation in the Hippocampus and Enhances Cognition

    PubMed Central

    Gu, Zhenglin; Yoshimura, Ryan F.; Villegier, Anne-Sophie; Hogenkamp, Derk J.; Whittemore, Edward R.; Huang, Jin-Cheng; Tran, Minhtam B.; Belluzzi, James D.; Yakel, Jerrel L.; Gee, Kelvin W.

    2011-01-01

    α5 Subunit-containing GABAA receptors (GABAARs) and α7 neuronal nicotinic-acetylcholine receptors (nAChRs) are members of the Cys-loop family of ligand-gated ion channels (LGICs) that mediate cognitive and attentional processes in the hippocampus. α5 GABAARs alter network activity by tonic inhibition of CA1/CA3 pyramidal cells of the hippocampus. Postsynaptic α7 nAChRs in the hippocampus regulate inhibitory GABAergic interneuron activity required for synchronization of pyramidal neurons in the CA1, whereas presynaptic α7 nAChRs regulate glutamate release. Can simultaneous allosteric modulation of these LGICs produce synergistic effects on cognition? We show that combined transient application of two allosteric modulators that individually 1) inhibit α5 GABAARs and 2) enhance α7 nAChRs causes long-term potentiation (LTP) of mossy fiber stimulation-induced excitatory postsynaptic currents (EPSC) from CA1 pyramidal neurons of rat hippocampal slices. The LTP effect evoked by two compounds is replicated by 3-(2,5-difluorophenyl)-6-(N-ethylindol-5-yl)-1,2,4-triazolo[4,3-b]pyridazine (522-054), a compound we designed to simultaneously inhibit α5 GABAARs and enhance α7 nAChRs. Selective antagonists for either receptor block sustained EPSC potentiation produced by 522-054. In vivo, 522-054 enhances performance in the radial arm maze and facilitates attentional states in the five-choice serial reaction time trial with similar receptor antagonist sensitivity. These observations may translate into therapeutic utility of dual action compounds in diseases of hippocampal-based cognitive impairment. PMID:21159751

  14. Dietary 2'-Fucosyllactose Enhances Operant Conditioning and Long-Term Potentiation via Gut-Brain Communication through the Vagus Nerve in Rodents.

    PubMed

    Vazquez, Enrique; Barranco, Alejandro; Ramirez, Maria; Gruart, Agnes; Delgado-Garcia, Jose M; Jimenez, Maria L; Buck, Rachael; Rueda, Ricardo

    2016-01-01

    2´-fucosyllactose (2´-FL) is an abundant human milk oligosaccharide (HMO) in human milk with diverse biological effects. We recently reported ingested 2´-FL stimulates central nervous system (CNS) function, such as hippocampal long term potentiation (LTP) and learning and memory in rats. Conceivably the effect of 2´-FL on CNS function may be via the gut-brain axis (GBA), specifically the vagus nerve, and L-fucose (Fuc) may play a role. This study had two aims: (1) determine if the effect of ingested 2´-FL on the modulation of CNS function is dependent on the integrity of the molecule; and (2) confirm if oral 2´-FL modified hippocampal LTP and associative learning related skills in rats submitted to bilateral subdiaphragmatic vagotomy. Results showed that 2´-FL but not Fuc enhanced LTP, and vagotomy inhibited the effects of oral 2´-FL on LTP and associative learning related paradigms. Taken together, the data show that dietary 2´-FL but not its Fuc moiety affects cognitive domains and improves learning and memory in rats. This effect is dependent on vagus nerve integrity, suggesting GBA plays a role in 2´-FL-mediated cognitive benefits.

  15. Baclofen-enhanced spinal cord stimulation and intrathecal baclofen alone for neuropathic pain: Long-term outcome of a pilot study.

    PubMed

    Lind, Göran; Schechtmann, Gastón; Winter, Jaleh; Meyerson, Björn A; Linderoth, Bengt

    2008-01-01

    In a previously published pilot study, we addressed the possibility to increase the effectiveness of spinal cord stimulation (SCS) applied for neuropathic pain by using adjunct pharmacological therapy. This combined treatment approach was a direct spin-off from animal experiments aiming at the exploration of transmitter and receptor mechanisms involved in the pain relieving effect of SCS. Out of 48 patients with neuropathic pain of peripheral origin responding poorly to SCS, seven received pumps for intrathecal baclofen (GABA-B receptor agonist) delivery together with SCS, and four had pumps alone. In order to assess the long-term effect a follow-up has been performed, with an average, total treatment time of 67 months. At the follow-up the remaining nine patients still enjoy about the same pain relief as initially, but with a mean, further dose increase of about 30%. This study demonstrates that a deficient SCS effect in neuropathic pain may be considerably improved by intrathecal baclofen administration, and that this enhanced effect persists for a long-time. On-going and future animal studies may provide new and even more efficient pharmaceutical candidates for such combined therapy.

  16. Bio-inspired oligovitronectin-grafted surface for enhanced self-renewal and long-term maintenance of human pluripotent stem cells under feeder-free conditions.

    PubMed

    Park, Hyun-Ji; Yang, Kisuk; Kim, Mun-Jung; Jang, Jiho; Lee, Mihyun; Kim, Dong-Wook; Lee, Haeshin; Cho, Seung-Woo

    2015-05-01

    Current protocols for human pluripotent stem cell (hPSC) expansion require feeder cells or matrices from animal sources that have been the major obstacle to obtain clinical grade hPSCs due to safety issues, difficulty in quality control, and high expense. Thus, feeder-free, chemically defined synthetic platforms have been developed, but are mostly confined to typical polystyrene culture plates. Here, we report a chemically defined, material-independent, bio-inspired surface coating allowing for feeder-free expansion and maintenance of self-renewal and pluripotency of hPSCs on various polymer substrates and devices. Polydopamine (pDA)-mediated immobilization of vitronectin (VN) peptides results in surface functionalization of VN-dimer/pDA conjugates. The engineered surfaces facilitate adhesion, proliferation, and colony formation of hPSCs via enhanced focal adhesion, cell-cell interaction, and biophysical signals, providing a chemically defined, xeno-free culture system for clonal expansion and long-term maintenance of hPSCs. This surface engineering enables the application of clinically-relevant hPSCs to a variety of biomedical systems such as tissue-engineering scaffolds and medical devices.

  17. Dietary 2’-Fucosyllactose Enhances Operant Conditioning and Long-Term Potentiation via Gut-Brain Communication through the Vagus Nerve in Rodents

    PubMed Central

    Vazquez, Enrique; Barranco, Alejandro; Ramirez, Maria; Gruart, Agnes; Delgado-Garcia, Jose M.; Jimenez, Maria L.; Buck, Rachael; Rueda, Ricardo

    2016-01-01

    2´-fucosyllactose (2´-FL) is an abundant human milk oligosaccharide (HMO) in human milk with diverse biological effects. We recently reported ingested 2´-FL stimulates central nervous system (CNS) function, such as hippocampal long term potentiation (LTP) and learning and memory in rats. Conceivably the effect of 2´-FL on CNS function may be via the gut-brain axis (GBA), specifically the vagus nerve, and L-fucose (Fuc) may play a role. This study had two aims: (1) determine if the effect of ingested 2´-FL on the modulation of CNS function is dependent on the integrity of the molecule; and (2) confirm if oral 2´-FL modified hippocampal LTP and associative learning related skills in rats submitted to bilateral subdiaphragmatic vagotomy. Results showed that 2´-FL but not Fuc enhanced LTP, and vagotomy inhibited the effects of oral 2´-FL on LTP and associative learning related paradigms. Taken together, the data show that dietary 2´-FL but not its Fuc moiety affects cognitive domains and improves learning and memory in rats. This effect is dependent on vagus nerve integrity, suggesting GBA plays a role in 2´-FL-mediated cognitive benefits. PMID:27851789

  18. Short-term enhancement and long-term suppression of denitrification in estuarine sediments receiving primary- and secondary-treated paper and pulp mill discharge.

    PubMed

    Oakes, Joanne M; Eyre, Bradley D; Ross, Donald J

    2011-04-15

    To determine the role of sediment denitrification in removing inputs of primary- (PE) and secondary-treated effluent (SE) from a pulp and paper mill (PPM), organic matter (OM) associated with PE (residual wood fiber) and SE (activated sludge biomass and phytoplankton) was added to estuarine intertidal sediments and denitrification rates were measured over 27 days. Labile sludge biomass and phytoplankton initially stimulated denitrification, including for pre-existing sediment N. After 2.5 d, however, denitrification was suppressed apparently due to microbial competition for N to process the refractory (high C:N) material remaining. Wood fiber suppressed denitrification throughout the experiment due to competition for N to process the refractory OM. Ultimate long-term denitrification suppression by phytoplankton is offset by initial enhanced denitrification rates. Although nutrient release during degradation of sludge biomass and wood fiber may stimulate phytoplankton production, N equivalent to 127% of the expected daily phytoplankton load was denitrified within 24 h, allowing for permanent removal of PPM-derived N. Compared to primary treatment, secondary treatment of PPM effluent has greater potential for N removal.

  19. Growth enhancement of Picea abies trees under long-term, low-dose N addition is due to morphological more than to physiological changes.

    PubMed

    Krause, Kim; Cherubini, Paolo; Bugmann, Harald; Schleppi, Patrick

    2012-12-01

    Human activities have drastically increased nitrogen (N) inputs into natural and near-natural terrestrial ecosystems such that critical loads are now being exceeded in many regions of the world. This implies that these ecosystems are shifting from natural N limitation to eutrophication or even N saturation. This process is expected to modify the growth of forests and thus, along with management, to affect their carbon (C) sequestration. However, knowledge of the physiological mechanisms underlying tree response to N inputs, especially in the long term, is still lacking. In this study, we used tree-ring patterns and a dual stable isotope approach (δ(13)C and δ(18)O) to investigate tree growth responses and the underlying physiological reactions in a long-term, low-dose N addition experiment (+23 kg N ha(-1) a(-1)). This experiment has been conducted for 14 years in a mountain Picea abies (L.) Karst. forest in Alptal, Switzerland, using a paired-catchment design. Tree stem C sequestration increased by ∼22%, with an N use efficiency (NUE) of ca. 8 kg additional C in tree stems per kg of N added. Neither earlywood nor latewood δ(13)C values changed significantly compared with the control, indicating that the intrinsic water use efficiency (WUE(i)) (A/g(s)) did not change due to N addition. Further, the isotopic signal of δ(18)O in early- and latewood showed no significant response to the treatment, indicating that neither stomatal conductance nor leaf-level photosynthesis changed significantly. Foliar analyses showed that needle N concentration significantly increased in the fourth to seventh treatment year, accompanied by increased dry mass and area per needle, and by increased tree height growth. Later, N concentration and height growth returned to nearly background values, while dry mass and area per needle remained high. Our results support the hypothesis that enhanced stem growth caused by N addition is mainly due to an increased leaf area index (LAI

  20. Acute renal failure induced by markedly decreased appetite secondary to a depressive episode after discontinuation of long-term lithium therapy in an elderly patient with bipolar disorder.

    PubMed

    Okada, Akira

    2014-05-16

    Some elderly patients on chronic lithium therapy for bipolar disorder and their doctors may be faced with a therapeutic dilemma over whether or not to continue prescribing/taking lithium given their increased risk of reduced renal function. We present the case of a 78-year-old woman with bipolar disorder who discontinued lithium therapy due to increased risk factors for renal injury. After discontinuation, she experienced markedly decreased appetite secondary to a depressive episode, and developed acute renal failure, which subsequently progressed to a more advanced stage of chronic kidney disease. This case suggests that extreme care must be taken to prevent the recurrence of depression in elderly patients with bipolar disorder who discontinue lithium therapy, even when they had been emotionally stable for a long time while receiving lithium. Medications other than lithium for bipolar disorder may be needed at the time lithium therapy is discontinued.

  1. Long-term outcomes after severe shock.

    PubMed

    Pratt, Cristina M; Hirshberg, Eliotte L; Jones, Jason P; Kuttler, Kathryn G; Lanspa, Michael J; Wilson, Emily L; Hopkins, Ramona O; Brown, Samuel M

    2015-02-01

    Severe shock is a life-threatening condition with very high short-term mortality. Whether the long-term outcomes among survivors of severe shock are similar to long-term outcomes of other critical illness survivors is unknown. We therefore sought to assess long-term survival and functional outcomes among 90-day survivors of severe shock and determine whether clinical predictors were associated with outcomes. Seventy-six patients who were alive 90 days after severe shock (received ≥1 μg/kg per minute of norepinephrine equivalent) were eligible for the study. We measured 3-year survival and long-term functional outcomes using the Medical Outcomes Study 36-Item Short-Form Health Survey, the EuroQOL 5-D-3L, the Hospital Anxiety and Depression Scale, the Impact of Event Scale-Revised, and an employment instrument. We also assessed the relationship between in-hospital predictors and long-term outcomes. The mean long-term survival was 5.1 years; 82% (62 of 76) of patients survived, of whom 49 were eligible for follow-up. Patients who died were older than patients who survived. Thirty-six patients completed a telephone interview a mean of 5 years after hospital admission. The patients' Physical Functioning scores were below U.S. population norms (P < 0.001), whereas mental health scores were similar to population norms. Nineteen percent of the patients had symptoms of depression, 39% had symptoms of anxiety, and 8% had symptoms of posttraumatic stress disorder. Thirty-six percent were disabled, and 17% were working full-time. Early survivors of severe shock had a high 3-year survival rate. Patients' long-term physical and psychological outcomes were similar to those reported for cohorts of less severely ill intensive care unit survivors. Anxiety and depression were relatively common, but only a few patients had symptoms of posttraumatic stress disorder. This study supports the observation that acute illness severity does not determine long-term outcomes. Even extremely

  2. Usefulness of the QRS-T angle to improve long-term risk stratification of patients with acute myocardial infarction and depressed left ventricular ejection fraction.

    PubMed

    Raposeiras-Roubín, Sergio; Virgós-Lamela, Alejandro; Bouzas-Cruz, Noelia; López-López, Andrea; Castiñeira-Busto, María; Fernández-Garda, Rita; García-Castelo, Alberto; Rodríguez-Mañero, Moisés; García-Acuña, José María; Abu-Assi, Emad; González-Juanatey, José Ramón

    2014-04-15

    In light of the low cost, the widespread availability of the electrocardiogram, and the increasing economic burden of the health-related problems, we aimed to analyze the prognostic value of automatic frontal QRS-T angle to predict mortality in patients with left ventricular (LV) systolic dysfunction after acute myocardial infarction (AMI). About 467 consecutive patients discharged with diagnosis of AMI and with LV ejection fraction ≤40% were followed during 3.9 years (2.1 to 5.9). From them, 217 patients (47.5%) died. The frontal QRS-T angle was higher in patients who died (116.6±52.8 vs 77.9±55.1, respectively, p<0.001). The QRS-T angle value of 90° was the most accurate to predict all-cause cardiac death. After multivariate analysis, frontal QRS-T angle remained as an excellent predictor of all-cause and cardiac deaths, increasing the mortality 6% per each 10°. For the global mortality, the hazard ratio for a QRS-T angle>90° was 2.180 (1.558 to 3.050), and for the combined end point of cardiac death and appropriate implantable cardioverter defribrillator therapy, it was 2.385 (1.570 to 3.623). This independent predictive value was maintained even after adjusting by bundle brunch block, ST-elevation AMI, and its localization. In conclusion, a wide automatic frontal QRS-T angle (>90°) is a good discriminator of long-term mortality in patients with LV systolic dysfunction after an AMI. The ability to easily measure it from a standard 12-lead electrocardiogram together with its prognostic value makes the frontal QRS-T angle an attractive tool to help clinicians to improve risk stratification of those patients.

  3. Long-term enhanced winter soil frost alters growing season CO2 fluxes through its impact on vegetation development in a boreal peatland.

    PubMed

    Zhao, Junbin; Peichl, Matthias; Nilsson, Mats B

    2017-01-11

    At high latitudes, winter climate change alters snow cover and, consequently, may cause a sustained change in soil frost dynamics. Altered winter soil conditions could influence the ecosystem exchange of carbon dioxide (CO2 ) and, in turn, provide feedbacks to ongoing climate change. To investigate the mechanisms that modify the peatland CO2 exchange in response to altered winter soil frost, we conducted a snow exclusion experiment to enhance winter soil frost and to evaluate its short-term (1-3 years) and long-term (11 years) effects on CO2 fluxes during subsequent growing seasons in a boreal peatland. In the first 3 years after initiating the treatment, no significant effects were observed on either gross primary production (GPP) or ecosystem respiration (ER). However, after 11 years, the temperature sensitivity of ER was reduced in the treatment plots relative to the control, resulting in an overall lower ER in the former. Furthermore, early growing season GPP was also lower in the treatment plots than in the controls during periods with photosynthetic photon flux density (PPFD) ≥800 μmol m(-2)  s(-1) , corresponding to lower sedge leaf biomass in the treatment plots during the same period. During the peak growing season, a higher GPP was observed in the treatment plots under the low light condition (i.e. PPFD 400 μmol m(-2)  s(-1) ) compared to the control. As Sphagnum moss maximizes photosynthesis at low light levels, this GPP difference between the plots may have been due to greater moss photosynthesis, as indicated by greater moss biomass production, in the treatment plots relative to the controls. Our study highlights the different responses to enhanced winter soil frost among plant functional types which regulate CO2 fluxes, suggesting that winter climate change could considerably alter the growing season CO2 exchange in boreal peatlands through its effect on vegetation development.

  4. Case presentation: long-term treatment.

    PubMed

    Glucksman, Myron L

    2013-01-01

    The long-term (14 years) psychodynamic psychotherapy and pharmacotherapy of a depressed, suicidal, self-mutilating female patient is described. Her diagnoses included Chronic Posttraumatic Stress Disorder, Borderline Personality Disorder, and Recurrent Major Depression. Treatment was punctuated with repeated hospitalizations for self-mutilation (cutting) and suicidal ideation. A major determinant for her psychopathology was sexual abuse by her father from ages 6 to 14. This resulted in feelings of guilt and rage that she repressed and acted out through self-mutilating and suicidal behavior. A prolonged negative transference gradually became ambivalent, then positive. This was associated with her internalization of the healing qualities of the therapeutic relationship. She also gained insight into the reasons for her need to punish herself. Her initial self-representation as unworthy and bad was transformed into perceiving herself as a worthwhile, loving person. This case illustrates the role of long-term treatment for a complex, life-threatening, psychiatric disorder.

  5. Protein-Pacing Caloric-Restriction Enhances Body Composition Similarly in Obese Men and Women during Weight Loss and Sustains Efficacy during Long-Term Weight Maintenance.

    PubMed

    Arciero, Paul J; Edmonds, Rohan; He, Feng; Ward, Emery; Gumpricht, Eric; Mohr, Alex; Ormsbee, Michael J; Astrup, Arne

    2016-07-30

    Short-Term protein-pacing (P; ~6 meals/day, >30% protein/day) and caloric restriction (CR, ~25% energy deficit) improves total (TBF), abdominal (ABF) and visceral (VAT) fat loss, energy expenditure, and biomarkers compared to heart healthy (HH) recommendations (3 meals/day, 15% protein/day) in obese adults. Less is known whether obese men and women respond similarly to P-CR during weight loss (WL) and whether a modified P-CR (mP-CR) is more efficacious than a HH diet during long-term (52 week) weight maintenance (WM). The purposes of this study were to evaluate the efficacy of: (1) P-CR on TBF, ABF, resting metabolic rate (RMR), and biomarkers between obese men and women during WL (weeks 0-12); and (2) mP-CR compared to a HH diet during WM (weeks 13-64). During WL, men (n = 21) and women (n = 19) were assessed for TBF, ABF, VAT, RMR, and biomarkers at weeks 0 (pre) and 12 (post). Men and women had similar reductions (p < 0.01) in weight (10%), TBF (19%), ABF (25%), VAT (33%), glucose (7%-12%), insulin (40%), leptin (>50%) and increase in % lean body mass (9%). RMR (kcals/kg bodyweight) was unchanged and respiratory quotient decreased 9%. Twenty-four subjects (mP-CR, n = 10; HH, n = 14) completed WM. mP-CR regained significantly less body weight (6%), TBF (12%), and ABF (17%) compared to HH (p < 0.05). Our results demonstrate P-CR enhances weight loss, body composition and biomarkers, and maintains these changes for 52-weeks compared to a traditional HH diet.

  6. Endocrine MPA enhances the effects of TAC chemotherapy on improvement of prognosis and increase in long-term survival rates for patients with endometrial cancer.

    PubMed

    Yuan, Xiuhong; Wang, L U; Xue, Juan; Li, L I; Zhang, Jing

    2015-09-01

    The aim of the present study was to investigate the effect of taxol, adriamycin and carboplatin (TAC) chemotherapy combined with endocrine medroxyprogesterone acetate (MPA) therapy for the treatment of patients with endometrial cancer. A retrospective analysis of 124 patients with endometrial cancer was performed by dividing the cohort into an experimental and control group. The 64 patients in the experimental group received TAC and MPA chemotherapy, whereas the 60 patients in the control group were treated with TAC chemotherapy only. Tissue samples scraped from the uterus were used to extract the total proteins and RNAs for the western blot and reverse transcription-quantitative polymerase chain reaction analyses, respectively. All the patients were followed up for 20-45 months, during which time prognostic data, and one- to three-year survival rates were recorded and compared. The rate of recurrence or metastasis was significantly lower in the experimental group compared with that in the control group (P<0.05) and the three-year survival rate of the experimental group was significantly higher than that of the control group (P<0.05). Furthermore, the mean metastasis-associated 1 (MTA1) protein and RNA expression levels were significantly lower in the experimental group compared with the control group (P<0.05), exhibiting ~30 and ~15% of the levels in the control group, respectively. Therefore, a treatment strategy of TAC chemotherapy combined with endocrine MPA therapy appears to effectively improve the prognosis and increase the long-term survival rates of patients with endometrial cancer. Such an enhancing effect may be mediated by the transcriptional downregulation of MTA1 expression.

  7. Enhanced co-tolerance and co-sensitivity from long-term metal exposures of heterotrophic and autotrophic components of fluvial biofilms.

    PubMed

    Tlili, Ahmed; Maréchal, Marjorie; Bérard, Annette; Volat, Bernadette; Montuelle, Bernard

    2011-09-15

    Understanding the interactive effects of multiple stressors on ecosystems has started to become a major concern. The aim of our study was therefore to evaluate the consequences of a long-term exposure to environmental concentrations of Cu, Zn and As on the pollution-induced community tolerance (PICT) of lotic biofilm communities in artificial indoor channels. Moreover, the specificity of the PICT was assessed by evaluating the positive and negative co-tolerance between these metals. Photosynthetic efficiency and substrate-induced respiration (SIR), targeting the autotrophic and heterotrophic communities respectively were used in short-term inhibition bioassays with Cu, Zn and As to assess sensitivities of pre-exposed biofilms to the metals tested. Diversity profiles of a phototrophic, eukaryotic and prokaryotic community in biofilms following the different treatments were determined and analyzed with principal component analysis. The results demonstrated that pre-exposure to metals induced structural shifts in the community and led to tolerance enhancements in the phototrophic and heterotrophic communities. On the other hand, whatever the functional parameter used (i.e. photosynthesis and SIR), communities exposed to Cu were more tolerant to Zn and vice versa. Furthermore, only phototrophic communities pre-exposed to As developed tolerance to Cu but not to Zn, whereas no co-tolerance between Cu and As was observed in the heterotrophic communities. Finally, phototrophic and heterotrophic communities exposed to Cu and Zn became more sensitive to As, reflecting a negative co-tolerance between these metals. Overall, our findings support the fact that although the mode of action of the different metals is an important driver for the structure and thus the tolerance of the communities, it appears that the detoxification modes are the most important factors for the occurrence of positive or negative co-tolerance.

  8. Long-term exposures to low doses of silver nanoparticles enhanced in vitro malignant cell transformation in non-tumorigenic BEAS-2B cells.

    PubMed

    Choo, Wun Hak; Park, Cho Hee; Jung, Shi Eun; Moon, Byeonghak; Ahn, Huiyeon; Ryu, Jung Seok; Kim, Keun-Soo; Lee, Yong Hwa; Yu, Il Je; Oh, Seung Min

    2016-12-01

    To predict carcinogenic potential of AgNPs on the respiratory system, BEAS-2B cells (human bronchial epithelial cells) were chronically exposed to low- and non-cytotoxic dose (0.13 and 1.33μg/ml) of AgNPs for 4months (#40 passages). To assess malignant cell transformation of chronic exposure to AgNPs, several bioassays including anchorage independent agar colony formation, cell migration/invasion assay, and epithelial-mesenchymal transition (EMT) were performed in BEAS-2B cells. Chronic exposure to AgNPs showed a significant increase of anchorage independent agar colony formation and cell migration/invasion. EMT, which is the loss of epithelial markers (E-Cadherin and Keratin) and the gain of mesenchymal marker (N-cadherin and Vimentin), was induced by chronic exposure to AgNPs. These responses indicated that chronic exposure to AgNPs could acquire characteristics of tumorigenic cells from normal BEAS-2B cells. In addition, caspase-3, p-p53, p-p38, and p-JNK were significantly decreased, while p-ERK1/2 was significantly increased. MMP-9 related to cell migration/invasion was upregulated, while a MMP-9 inhibitor, TIMP-1 was down-regulated. These results indicated that BEAS-2B cells exposed to AgNPs could induce anti-apoptotic response/anoikis resistance, and cell migration/invasion by complex regulation of MAPK kinase (p38, JNK, and ERK) and p53 signaling pathways. Therefore, we suggested that long-term exposure to low-dose of AgNPs could enhance malignant cell transformation in non-tumorigenic BEAS-2B cells. Our findings provide useful information needed to assess the carcinogenic potential of AgNPs.

  9. Protein-Pacing Caloric-Restriction Enhances Body Composition Similarly in Obese Men and Women during Weight Loss and Sustains Efficacy during Long-Term Weight Maintenance

    PubMed Central

    Arciero, Paul J.; Edmonds, Rohan; He, Feng; Ward, Emery; Gumpricht, Eric; Mohr, Alex; Ormsbee, Michael J.; Astrup, Arne

    2016-01-01

    Short-Term protein-pacing (P; ~6 meals/day, >30% protein/day) and caloric restriction (CR, ~25% energy deficit) improves total (TBF), abdominal (ABF) and visceral (VAT) fat loss, energy expenditure, and biomarkers compared to heart healthy (HH) recommendations (3 meals/day, 15% protein/day) in obese adults. Less is known whether obese men and women respond similarly to P-CR during weight loss (WL) and whether a modified P-CR (mP-CR) is more efficacious than a HH diet during long-term (52 week) weight maintenance (WM). The purposes of this study were to evaluate the efficacy of: (1) P-CR on TBF, ABF, resting metabolic rate (RMR), and biomarkers between obese men and women during WL (weeks 0–12); and (2) mP-CR compared to a HH diet during WM (weeks 13–64). During WL, men (n = 21) and women (n = 19) were assessed for TBF, ABF, VAT, RMR, and biomarkers at weeks 0 (pre) and 12 (post). Men and women had similar reductions (p < 0.01) in weight (10%), TBF (19%), ABF (25%), VAT (33%), glucose (7%–12%), insulin (40%), leptin (>50%) and increase in % lean body mass (9%). RMR (kcals/kg bodyweight) was unchanged and respiratory quotient decreased 9%. Twenty-four subjects (mP-CR, n = 10; HH, n = 14) completed WM. mP-CR regained significantly less body weight (6%), TBF (12%), and ABF (17%) compared to HH (p < 0.05). Our results demonstrate P-CR enhances weight loss, body composition and biomarkers, and maintains these changes for 52-weeks compared to a traditional HH diet. PMID:27483317

  10. Extracellular-signal regulated kinase 1-dependent metabotropic glutamate receptor 5-induced long-term depression in the bed nucleus of the stria terminalis is disrupted by cocaine administration.

    PubMed

    Grueter, Brad A; Gosnell, Heather B; Olsen, Christopher M; Schramm-Sapyta, Nicole L; Nekrasova, Tanya; Landreth, Gary E; Winder, Danny G

    2006-03-22

    The bed nucleus of the stria terminalis (BNST) is a key component of the CNS stress and reward circuit. Synaptic plasticity in this region could in part underlie the persistent behavioral alterations in generalized anxiety and addiction. Group I metabotropic glutamate receptors (mGluRs) have been implicated in stress, addiction, and synaptic plasticity, but their roles in the BNST are unknown. We find that activation of group I mGluRs in the dorsal BNST induces depression of excitatory synaptic transmission through two distinct mechanisms. First, a combined activation of group I mGluRs (mGluR1 and mGluR5) induces a transient depression that is cannabinoid 1 receptor dependent. Second, as with endocannabinoid-independent group I mGluR long-term depression (LTD) in the adult hippocampus, we find that activation of mGluR5 induces an extracellular signal-regulated kinase (ERK)-dependent LTD. Surprisingly, our data demonstrate that this LTD requires the ERK1 rather than ERK2 isoform, establishing a key role for this isoform in the CNS. Finally, we find that this LTD is dramatically reduced after multiple exposures but not a single exposure to cocaine, suggesting a role for this form of plasticity in the actions of psychostimulants on anxiety and reward circuitries and their emergent control of animal behavior.

  11. Long term therapy of generalized anxiety disorder.

    PubMed

    Rouillon, Frédéric

    2004-04-01

    Generalized anxiety disorder (GAD) is a common (lifetime prevalence: 5.1%), recurrent condition, which often heralds other psychiatric disorders, notably depression. As by definition it is a disorder progressing over months, treatment should be designed on a long term basis. And yet, few studies have been conducted beyond the classical 6-8 weeks characterizing the acute treatment phase. This is especially true of anxiolytics, but also of antidepressants, with the exception of paroxetine and venlafaxine, which are the only drugs approved in this indication in Western countries. The efficacy of psychotherapy, notably relaxation and cognitive-behavioral therapy, is established in the treatment of GAD, but its preferred indications and possible combination with antidepressants are still to be specified. Long term, not to say very long term studies of GAD, as well as depression, will still be required in the future to improve its management and specify therapeutic modalities (combination treatment, optimal duration, continuous or intermittent therapy, choice of psychotherapeutic techniques or agents, em leader ). Early and adequately prolonged treatment should not only result in more numerous remission periods, but also in decreased frequency of co-morbidities whether depressive, addictive, or of another nature, and should also reduce the social impact of GAD.

  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. Long-term urethral catheterisation.

    PubMed

    Turner, Bruce; Dickens, Nicola

    This article discusses long-term urethral catheterisation, focusing on the relevant anatomy and physiology, indications for the procedure, catheter selection and catheter care. It is important that nurses have a good working knowledge of long-term catheterisation as the need for this intervention will increase with the rise in chronic health conditions and the ageing population.

  14. 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

  15. Hungry Horse Dam Wildlife Habitat Enhancement Project: Long-Term Habitat Management Plan, Elk and Mule Deer Winter Range Enhancement, Firefighter Mountain and Spotted Bear Winter Ranges.

    SciTech Connect

    Casey, Daniel; Malta, Patrick

    1990-06-01

    Project goals are to rehabilitate 1120 acres of big game (elk and mule deer, Odocoileus hemionus) winter range on the Hungry Horse and Spotted Bear Districts of Flathead National Forest lands adjacent to Hungry Horse Reservoir. This project represents the initial phase of implementation toward the mitigation goal. A minimum of 547 acres Trust-funded enhancements are called for in this plan. The remainder are part of the typical Forest Service management activities for the project area. Monitor and evaluate the effects of project implementation on the big game forage base and elk and mule deer populations in the project area. Monitor enhancement success to determine effective acreage to be credited against mitigation goal. Additional enhancement acreage will be selected elsewhere in the Flathead Forest or other lands adjacent'' to the reservoir based on progress toward the mitigation goal as determined through monitoring. The Wildlife Mitigation Trust Fund Advisory Committee will serve to guide decisions regarding future enhancement efforts. 7 refs.

  16. A metabolic strategy to enhance long-term survival by Phx1 through stationary phase-specific pyruvate decarboxylases in fission yeast.

    PubMed

    Kim, Ji-Yoon; Kim, Eun-Jung; Lopez-Maury, Luis; Bähler, Jürg; Roe, Jung-Hye

    2014-07-01

    In the fission yeast Schizosaccharomyces pombe, the stationary phase-specific transcription factor Phx1 contributes to long-term survival, stress tolerance, and meiosis. We identified Phx1-dependent genes through transcriptome analysis, and further analyzed those related with carbohydrate and thiamine metabolism, whose expression decreased in ∆phx1. Consistent with mRNA changes, the level of thiamine pyrophosphate (TPP) and TPP-utilizing pyruvate decarboxylase activity that converts pyruvate to acetaldehyde were also reduced in the mutant. Therefore, Phx1 appears to shift metabolic flux by diverting pyruvate from the TCA cycle and respiration to ethanol fermentation. Among the four predicted genes for pyruvate decarboxylase, only the Phx1-dependent genes (pdc201+ and pdc202+) contributed to long-term survival as judged by mutation and overexpression studies. These findings indicate that the Phx1-mediated long-term survival is achieved primarily through increasing the synthesis and activity of pyruvate decarboxylase. Consistent with this hypothesis, we observed that Phx1 curtailed respiration when cells entered stationary phase. Introduction of Δphx1 mutation compromised the long-lived phenotypes of Δpka1 and Δsck2 mutants that are devoid of pro-aging kinases of nutrient-signalling pathways, and of the Δpyp1 mutant with constitutively activated stress-responsive kinase Sty1. Therefore, achievement of long-term viability through both nutrient limitation and anti-stress response appears to be dependent on Phx1.

  17. Long-Term, Open-Label, Safety Study of Edivoxetine 12 to 18 mg Once Daily as Adjunctive Treatment for Patients With Major Depressive Disorder Who Are Partial Responders to Selective Serotonin Reuptake Inhibitor Treatment.

    PubMed

    Ball, Susan G; Atkinson, Sarah; Sparks, JonDavid; Bangs, Mark; Goldberger, Celine; Dubé, Sanjay

    2015-06-01

    Long-term safety, tolerability, and efficacy of adjunctive edivoxetine hydrochloride (hereafter edivoxetine), a highly selective and potent norepinephrine reuptake inhibitor, was assessed in patients with major depressive disorder (MDD) experiencing partial response to selective serotonin reuptake inhibitor treatment. Data are from a multicenter, 54-week, open-label trial of adjunctive edivoxetine 12 to 18 mg once daily in patients with MDD who had experienced partial response by history to 6 or more weeks of current selective serotonin reuptake inhibitor therapy and who had a 17-item GRID Hamilton Rating Scale for Depression total score 16 or higher at study entry. Safety measures included discontinuation rate, treatment-emergent adverse events, serious adverse events, and vital signs. Efficacy measures included the Montgomery-Åsberg Depression Rating Scale. Of 608 patients, 328 (54%) completed the open-label adjunctive treatment. Study discontinuation due to adverse events occurred in 17.0%, and there were 13 serious adverse events (1 death). Treatment-emergent adverse events 5% or higher were nausea, hyperhidrosis, constipation, headache, dry mouth, dizziness, vomiting, insomnia, and upper respiratory tract infection. Mean increases were observed in systolic blood pressure (range, 0.0-2.3 mm Hg), diastolic blood pressure (range, 1.9-3.3 mm Hg), and pulse (range, 5.9-8.4 beats per minute). Mean improvements on the Montgomery-Åsberg Depression Rating Scale (-17.0) were observed from baseline to week 54. The safety profile from this study provides an overview of outcomes associated with edivoxetine and norepinephrine reuptake inhibition as an adjunctive treatment in patients with MDD who were treated up to 1 year.

  18. Tolerance to Ethanol or Nicotine Results in Increased Ethanol Self-Administration and Long-Term Depression in the Dorsolateral Striatum.

    PubMed

    Abburi, Chandrika; Wolfman, Shannon L; Metz, Ryan A E; Kamber, Rinya; McGehee, Daniel S; McDaid, John

    2016-01-01

    Ethanol (EtOH) and nicotine are the most widely coabused drugs. Tolerance to EtOH intoxication, including motor impairment, results in greater EtOH consumption and may result in a greater likelihood of addiction. Previous studies suggest that cross-tolerance between EtOH and nicotine may contribute to the abuse potential of these drugs. Here we demonstrate that repeated intermittent administration of either EtOH or nicotine in adult male Sprague Dawley rats results in tolerance to EtOH-induced motor impairment and increased EtOH self-administration. These findings suggest that nicotine and EtOH cross-tolerance results in decreased aversive and enhanced rewarding effects of EtOH. Endocannabinoid signaling in the dorsolateral striatum (DLS) has been implicated in both EtOH tolerance and reward, so we investigated whether nicotine or EtOH pretreatment might modulate endocannabinoid signaling in this region. Using similar EtOH and nicotine pretreatment methods resulted in increased paired-pulse ratios of evoked EPSCs in enkephalin-positive medium spiny neurons in DLS slices. Thus, EtOH and nicotine pretreatment may modulate glutamatergic synapses in the DLS presynaptically. Bath application of the CB1 receptor agonist Win 55,2-212 increased the paired-pulse ratio of evoked EPSCs in control slices, while Win 55,2-212 had no effect on paired-pulse ratio in slices from either EtOH- or nicotine-pretreated rats. Consistent with these effects, nicotine pretreatment occluded LTD induction by high-frequency stimulation of the corticostriatal inputs to the dorsolateral striatum. These results suggest that nicotine and EtOH pretreatment modulates striatal synapses to induce tolerance to the motor-impairing effects of EtOH, which may contribute to nicotine and EtOH coabuse.

  19. Tolerance to Ethanol or Nicotine Results in Increased Ethanol Self-Administration and Long-Term Depression in the Dorsolateral Striatum

    PubMed Central

    Abburi, Chandrika; Wolfman, Shannon L.; Metz, Ryan A. E.; Kamber, Rinya

    2016-01-01

    Abstract Ethanol (EtOH) and nicotine are the most widely coabused drugs. Tolerance to EtOH intoxication, including motor impairment, results in greater EtOH consumption and may result in a greater likelihood of addiction. Previous studies suggest that cross-tolerance between EtOH and nicotine may contribute to the abuse potential of these drugs. Here we demonstrate that repeated intermittent administration of either EtOH or nicotine in adult male Sprague Dawley rats results in tolerance to EtOH-induced motor impairment and increased EtOH self-administration. These findings suggest that nicotine and EtOH cross-tolerance results in decreased aversive and enhanced rewarding effects of EtOH. Endocannabinoid signaling in the dorsolateral striatum (DLS) has been implicated in both EtOH tolerance and reward, so we investigated whether nicotine or EtOH pretreatment might modulate endocannabinoid signaling in this region. Using similar EtOH and nicotine pretreatment methods resulted in increased paired-pulse ratios of evoked EPSCs in enkephalin-positive medium spiny neurons in DLS slices. Thus, EtOH and nicotine pretreatment may modulate glutamatergic synapses in the DLS presynaptically. Bath application of the CB1 receptor agonist Win 55,2-212 increased the paired-pulse ratio of evoked EPSCs in control slices, while Win 55,2-212 had no effect on paired-pulse ratio in slices from either EtOH- or nicotine-pretreated rats. Consistent with these effects, nicotine pretreatment occluded LTD induction by high-frequency stimulation of the corticostriatal inputs to the dorsolateral striatum. These results suggest that nicotine and EtOH pretreatment modulates striatal synapses to induce tolerance to the motor-impairing effects of EtOH, which may contribute to nicotine and EtOH coabuse. PMID:27517088

  20. Long term complications of diabetes

    MedlinePlus

    ... medlineplus.gov/ency/patientinstructions/000327.htm Long-term complications of diabetes To use the sharing features on this page, ... other tests. All these may help you keep complications of diabetes away. You will need to check your blood ...

  1. Surface Engineering of Polycrystalline Silicon for Long-term Mechanical Stress Endurance Enhancement in Flexible Low Temperature Poly-Si Thin-Film Transistors.

    PubMed

    Chen, Bo-Wei; Chang, Ting-Chang; Hung, Yu-Ju; Huang, Shin-Ping; Chen, Hua-Mao; Liao, Po-Yung; Lin, Yu-Ho; Huang, Hui-Chun; Chiang, Hsiao-Cheng; Yang, Chung-I; Zheng, Yu-Zhe; Chu, Ann-Kuo; Li, Hung-Wei; Tsai, Chih-Hung; Lu, Hsueh-Hsing; Wang, Terry Tai-Jui; Chang, Tsu-Chiang

    2017-02-08

    Surface morphology in polycrystalline silicon (poly-Si) film is an issue regardless of whether conventional excimer laser annealing (ELA) or the newer metal-induced lateral crystallization (MILC) process is used. This paper investigates the stress distribution while undergoing long-term mechanical stress and the influence of stress on electrical characteristics. Our simulated results show that the non-uniform stress in the gate insulator is more pronounced near the polysilicon/gate insulator edge and at the two sides of the polysilicon protrusion. This stress results in defects in the gate insulator and leads to a non-uniform degradation phenomenon, which affects both the performance and reliability in thin-film transistors (TFTs). The degree of degradation is similar regardless of bending axis (channel-length axis, channel-width axis) or bending type (compression, tension), which means that the degradation is dominated by the protrusion effects. Furthermore, by utilizing long-term electrical bias stresses after undergoing long-tern bending stress, it is apparent that the carrier injection is severe in the sub-channel region, which confirms that the influence of protrusions is crucial. To eliminate the influence of surface morphology in poly-Si, three kinds of laser energy density were used during crystallization to control the protrusion height. The device with lowest protrusions demonstrates the smallest degradation after undergoing long-term bending.

  2. Impacts of long-term enhanced UV-B radiation on bryophytes in two sub-Arctic heathland sites of contrasting water availability

    PubMed Central

    Arróniz-Crespo, M.; Gwynn-Jones, D.; Callaghan, T. V.; Núñez-Olivera, E.; Martínez-Abaigar, J.; Horton, P.; Phoenix, G. K.

    2011-01-01

    Background and Aims Anthropogenic depletion of stratospheric ozone in Arctic latitudes has resulted in an increase of ultraviolet-B radiation (UV-B) reaching the biosphere. UV-B exposure is known to reduce above-ground biomass and plant height, to increase DNA damage and cause accumulation of UV-absorbing compounds in polar plants. However, many studies on Arctic mosses tended to be inconclusive. The importance of different water availability in influencing UV-B impacts on lower plants in the Arctic has been poorly explored and might partially explain the observed wide variation of responses, given the importance of water in controlling bryophyte physiology. This study aimed to assess the long-term responses of three common sub-Arctic bryophytes to enhanced UV-B radiation (+UV-B) and to elucidate the influence of water supply on those responses. Methods Responses of three sub-Arctic bryophytes (the mosses Hylocomium splendens and Polytrichum commune and the liverwort Barbilophozia lycopodioides) to +UV-B for 15 and 13 years were studied in two field experiments using lamps for UV-B enhancement with identical design and located in neighbouring areas with contrasting water availability (naturally mesic and drier sites). Responses evaluated included bryophyte abundance, growth, sporophyte production and sclerophylly; cellular protection by accumulation of UV-absorbing compounds, β-carotene, xanthophylls and development of non-photochemical quenching (NPQ); and impacts on photosynthesis performance by maximum quantum yield (Fv /Fm) and electron transport rate (ETR) through photosystem II (PSII) and chlorophyll concentrations. Results Responses were species specific: H. splendens responded most to +UV-B, with reduction in both annual growth (–22 %) and sporophyte production (–44 %), together with increased β-carotene, violaxanthin, total chlorophyll and NPQ, and decreased zeaxanthin and de-epoxidation of the xanthophyll cycle pool (DES). Barbilophozia

  3. A Relationship between Reduced Nucleus Accumbens Shell and Enhanced Lateral Hypothalamic Orexin Neuronal Activation in Long-Term Fructose Bingeing Behavior

    PubMed Central

    Rorabaugh, Jacki M.; Stratford, Jennifer M.; Zahniser, Nancy R.

    2014-01-01

    Fructose accounts for 10% of daily calories in the American diet. Fructose, but not glucose, given intracerebroventricularly stimulates homeostatic feeding mechanisms within the hypothalamus; however, little is known about how fructose affects hedonic feeding centers. Repeated ingestion of sucrose, a disaccharide of fructose and glucose, increases neuronal activity in hedonic centers, the nucleus accumbens (NAc) shell and core, but not the hypothalamus. Rats given glucose in the intermittent access model (IAM) display signatures of hedonic feeding including bingeing and altered DA receptor (R) numbers within the NAc. Here we examined whether substituting fructose for glucose in this IAM produces bingeing behavior, alters DA Rs and activates hedonic and homeostatic feeding centers. Following long-term (21-day) exposure to the IAM, rats given 8–12% fructose solutions displayed fructose bingeing but unaltered DA D1R or D2R number. Fructose bingeing rats, as compared to chow bingeing controls, exhibited reduced NAc shell neuron activation, as determined by c-Fos-immunoreactivity (Fos-IR). This activation was negatively correlated with orexin (Orx) neuron activation in the lateral hypothalamus/perifornical area (LH/PeF), a brain region linking homeostatic to hedonic feeding centers. Following short-term (2-day) access to the IAM, rats exhibited bingeing but unchanged Fos-IR, suggesting only long-term fructose bingeing increases Orx release. In long-term fructose bingeing rats, pretreatment with the Ox1R antagonist SB-334867 (30 mg/kg; i.p.) equally reduced fructose bingeing and chow intake, resulting in a 50% reduction in calories. Similarly, in control rats, SB-334867 reduced chow/caloric intake by 60%. Thus, in the IAM, Ox1Rs appear to regulate feeding based on caloric content rather than palatability. Overall, our results, in combination with the literature, suggest individual monosaccharides activate distinct neuronal circuits to promote feeding behavior

  4. Enhanced In Vitro Biocompatibility of Chemically Modified Poly(dimethylsiloxane) Surfaces for Stable Adhesion and Long-term Investigation of Brain Cerebral Cortex Cells.

    PubMed

    Kuddannaya, Shreyas; Bao, Jingnan; Zhang, Yilei

    2015-11-18

    Studies on the mammalian brain cerebral cortex have gained increasing importance due to the relevance of the region in controlling critical higher brain functions. Interactions between the cortical cells and surface extracellular matrix (ECM) proteins play a pivotal role in promoting stable cell adhesion, growth, and function. Poly(dimethylsiloxane) (PDMS) based platforms have been increasingly used for on-chip in vitro cellular system analysis. However, the inherent hydrophobicity of the PDMS surface has been unfavorable for any long-term cell system investigations due to transitory physical adsorption of ECM proteins on PDMS surfaces followed by eventual cell dislodgement due to poor anchorage and viability. To address this critical issue, we employed the (3-aminopropyl)triethoxysilane (APTES) based cross-linking strategy to stabilize ECM protein immobilization on PDMS. The efficiency of surface modification in supporting adhesion and long-term viability of neuronal and glial cells was analyzed. The chemically modified surfaces showed a relatively higher cell survival with an increased neurite length and neurite branching. These changes were understood in terms of an increase in surface hydrophilicity, protein stability, and cell-ECM protein interactions. The modification strategy could be successfully applied for stable cortical cell culture on the PDMS microchip for up to 3 weeks in vitro.

  5. Immunosuppression via Loss of IL2rγ Enhances Long-Term Functional Integration of hESC-Derived Photoreceptors in the Mouse Retina.

    PubMed

    Zhu, Jie; Cifuentes, Helen; Reynolds, Joseph; Lamba, Deepak A

    2017-03-02

    Loss of photoreceptors is a common endpoint in degenerative retinal diseases. Human pluripotent stem cells provide a potential source for photoreceptor replacement, but, even in mouse models, the efficiency and efficacy of transplantation-based repair remains poor. In this study, we examined the degree to which immune rejection contributes to these disappointing outcomes using an immunodeficient IL2 receptor γ (IL2rγ)-null mouse model. Our results show that prevention of cell rejection in the normal and degenerating retinal environment significantly improves long-term survival and integration of hESC-derived donor retinal cells. Transplanted cells are able to differentiate into mature photoreceptors expressing various opsins and can functionally integrate into congenitally blind mice. Our work suggests that even though the retina is often considered immune-privileged, suppression of host immune-mediated cell rejection may well be a useful approach for improving long-term integration of transplanted cells with a view to successful clinical outcomes.

  6. Spontaneous liver fibrosis induced by long term dietary vitamin D deficiency in adult mice is related to chronic inflammation and enhanced apoptosis.

    PubMed

    Zhu, Longdong; Kong, Ming; Han, Yuan-Ping; Bai, Li; Zhang, Xiaohui; Chen, Yu; Zheng, Sujun; Yuan, Hong; Duan, Zhongping

    2015-05-01

    Epidemiological studies have revealed an association between vitamin D deficiency and various chronic liver diseases. However, it is not known whether lack of vitamin D can induce spontaneous liver fibrosis in an animal model. To study this, mice were fed either a control diet or a vitamin D deficient diet (VDD diet). For the positive control, liver fibrosis was induced with carbon tetrachloride. Here we show, for the first time, that liver fibrosis spontaneously developed in mice fed the VDD diet. Long-term administration of a VDD diet resulted in necro-inflammation and liver fibrosis. Inflammatory mediators including tumor necrosis factor-α, interleulin-1, interleukin-6, Toll-like-receptor 4, and monocyte chemotactic protein-1 were up-regulated in the livers of the mice fed the VDD diet. Conversely, the expression of Th2/M2 markers such as IL-10, IL-13, arginase 1, and heme oxygenase-1 were down-regulated in the livers of mice fed the VDD diet. Transforming growth factor-β1 and matrix metalloproteinase 13, which are important for fibrosis, were induced in the livers of mice fed the VDD diet. Moreover, the VDD diet triggered apoptosis in the parenchymal cells, in agreement with the increased levels of Fas and FasL, and decreased Bcl2 and Bclx. Thus, long-term vitamin D deficiency can provoke chronic inflammation that can induce liver apoptosis, which consequently activates hepatic stellate cells to initiate liver fibrosis.

  7. Chelation of hippocampal zinc enhances long-term potentiation and synaptic tagging/capture in CA1 pyramidal neurons of aged rats: implications to aging and memory.

    PubMed

    Shetty, Mahesh Shivarama; Sharma, Mahima; Sajikumar, Sreedharan

    2017-02-01

    Aging is associated with decline in cognitive functions, prominently in the memory consolidation and association capabilities. Hippocampus plays a crucial role in the formation and maintenance of long-term associative memories, and a significant body of evidence shows that impairments in hippocampal function correlate with aging-related memory loss. A number of studies have implicated alterations in hippocampal synaptic plasticity, such as long-term potentiation (LTP), in age-related cognitive decline although exact mechanisms underlying are not completely clear. Zinc deficiency and the resultant adverse effects on cognition have been well studied. However, the role of excess of zinc in synaptic plasticity, especially in aging, is not addressed well. Here, we have investigated the hippocampal zinc levels and the impairments in synaptic plasticity, such as LTP and synaptic tagging and capture (STC), in the CA1 region of acute hippocampal slices from 82- to 84-week-old male Wistar rats. We report increased zinc levels in the hippocampus of aged rats and also deficits in the tetani-induced and dopaminergic agonist-induced late-LTP and STC. The observed deficits in synaptic plasticity were restored upon chelation of zinc using a cell-permeable chelator. These data suggest that functional plasticity and associativity can be successfully established in aged neural networks by chelating zinc with cell-permeable chelating agents.

  8. 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

  9. Sharpened cortical tuning and enhanced cortico-cortical communication contribute to the long-term neural mechanisms of visual motion perceptual learning.

    PubMed

    Chen, Nihong; Bi, Taiyong; Zhou, Tiangang; Li, Sheng; Liu, Zili; Fang, Fang

    2015-07-15

    Much has been debated about whether the neural plasticity mediating perceptual learning takes place at the sensory or decision-making stage in the brain. To investigate this, we trained human subjects in a visual motion direction discrimination task. Behavioral performance and BOLD signals were measured before, immediately after, and two weeks after training. Parallel to subjects' long-lasting behavioral improvement, the neural selectivity in V3A and the effective connectivity from V3A to IPS (intraparietal sulcus, a motion decision-making area) exhibited a persistent increase for the trained direction. Moreover, the improvement was well explained by a linear combination of the selectivity and connectivity increases. These findings suggest that the long-term neural mechanisms of motion perceptual learning are implemented by sharpening cortical tuning to trained stimuli at the sensory processing stage, as well as by optimizing the connections between sensory and decision-making areas in the brain.

  10. An enhanced model of the contemporary and long-term (200 ka) sublimation of the massive subsurface ice in Beacon Valley, Antarctica

    NASA Astrophysics Data System (ADS)

    Liu, Lu; Sletten, Ronald S.; Hagedorn, Birgit; Hallet, Bernard; McKay, Christopher P.; Stone, John O.

    2015-08-01

    A massive ice body buried under several decimeters of dry regolith in Beacon Valley, Antarctica, is believed to be more than 1 Ma old and perhaps over 8.1 Ma; however, vapor diffusion models suggest that subsurface ice in this region is not stable under current climate conditions. To better understand the controls on sublimation rates and stability of this massive ice, we have modeled vapor diffusion using 12 years of climate and soil temperature data from 1999 to 2011, including field measurements of episodic snow cover and snowmelt events that have not been represented in previous models of ground ice sublimation. The model is then extended to reconstruct the sublimation history over the last 200 ka using paleotemperatures estimated from ice core data from nearby Taylor Dome and a relationship between atmospheric temperature and humidity derived from our meteorological records. The model quantifies the impact of episodic snow events; they account for a nearly 30% reduction in the massive ice loss. The sublimation rate of ground ice averages 0.11 mm a-1 between 1999 and 2011 in Beacon Valley. Parameterized with past environmental conditions and assuming the same regolith thickness, the modeled sublimation rate of ground ice in Beacon Valley averages 0.09 mm a-1 for the last 200 ka, comparable to the long-term average rate estimated independently from various studies based on cosmogenic isotopes. This study provides a realistic estimate of the long-term sublimation history and supports the inference that the buried ice in Beacon Valley is older than 1 Ma.

  11. Three-dimensional printing of rhBMP-2-loaded scaffolds with long-term delivery for enhanced bone regeneration in a rabbit diaphyseal defect.

    PubMed

    Shim, Jin-Hyung; Kim, Se Eun; Park, Ju Young; Kundu, Joydip; Kim, Sung Won; Kang, Seong Soo; Cho, Dong-Woo

    2014-07-01

    In this study, recombinant human bone morphogenetic protein-2 (rhBMP-2) delivery system with slow mode was successfully developed in three-dimensional (3D) printing-based polycaprolactone (PCL)/poly(lactic-co-glycolic acid) (PLGA) scaffolds for bone formation of critical-sized rabbit segmental diaphyseal defect. To control the delivery of the rhBMP-2, collagen (for long-term delivery up to 28 days) and gelatin (for shor-term delivery within a week) solutions encapsulating rhBMP-2 were dispensed into a hollow cylinderical type of PCL/PLGA scaffold. An effective dose of 5μg/mL was determined by measuring the alkaline phosphatase and osteocalcin gene expression levels of human nasal inferior turbinate-derived mesenchymal stromal cells (hTMSCs) seeded on the PCL/PLGA/collagen scaffold in vitro. However, it was found that a burst release of rhBMP-2 from the PCL/PLGA/gelatin scaffold did not induce the osteogenic differentiation of hTMSCs in vitro at an equivalent dose. In the in vivo animal experiements, microcomputed tomography and histological analyses confirmed that PCL/PLGA/collagen/rhBMP-2 scaffolds (long-term delivery mode) showed the best bone healing quality at both weeks 4 and 8 after implantation without inflammatory response. On the other hand, a large number of macrophages indicating severe inflammation provoked by burst release of rhBMP-2 were observed in the vicinity of PCL/PLGA/gelatin/rhBMP-2 (short-term delivery mode) at week 4.

  12. Long-term effect of low concentration Cr(VI) on P removal in granule-based enhanced biological phosphorus removal (EBPR) system.

    PubMed

    Fang, Jing; Su, Bin; Sun, Peide; Lou, Juqing; Han, Jingyi

    2015-02-01

    In light of the fact that most wastewater in China contained both industrial and domestic wastewater, a 52-d systematical investigation was conducted on the long-term effect of low concentration Cr(VI) (0.3-0.8 mg L(-1)) on P removal performance of granule-based EBPR system in this study. The mechanisms were likewise discussed. Results showed that high Cr(VI) concentration (⩾0.5 mg L(-1)) could significantly inhibit P removal, while this phenomenon was not found when Cr(VI) concentration was less than (or equal to) 0.4 mg L(-1). Most of the granules was disintegrated and filamentous bacteria overgrew inducing sludge bulking occurred at 0.7 mg L(-1) Cr(VI). During the exposure test, the abundance of poly-phosphate-accumulating organisms (PAOs) significantly decreased while the populations of glycogen accumulating organisms (GAOs) and other bacteria increased. Both production and degradation of poly-β-hydroxyakanoates (PHAs) were apparently inhibited. An improved polysaccharide/protein (PS/PN) ratio was observed with the increasing Cr(VI) concentration, implying excessive polysaccharide was secreted by microorganisms to support its resistance to the toxicity of Cr(VI). Besides, good linear regression between PS/PN ratio and the granule size (R(2)=-0.86, p<0.01) was obtained, indicating that high PS/PN was adverse to granule stability. Correlation analysis indicated that the accumulation of granules intracellular Cr was directly responsible for the observed inhibitory effect on P removal process. The long-term Cr(VI) treatment had irreversible effects on granule-based EBPR system as it could not revive after a 16-d recovery process.

  13. Enhancement of denitrifying phosphorus removal and microbial community of long-term operation in an anaerobic anoxic oxic-biological contact oxidation system.

    PubMed

    Zhang, Miao; Yang, Qing; Zhang, Jianhua; Wang, Cong; Wang, Shuying; Peng, Yongzhen

    2016-10-01

    A two-sludge system consisting of anaerobic anoxic oxic-biological contact oxidation (A(2)/O-BCO) was developed to treat domestic wastewater with a low carbon/nitrogen (COD/TN) ratio (around 3.21) by shortening sludge retention time (SRT) for phosphorus accumulating organisms (PAOs) in the A(2)/O reactor and prolonging SRT for nitrifiers in the BCO reactor. Specifically, the BCO reactor was composed of three stages in series (N1, N2 and N3), so that simultaneous nitrogen and phosphorus removals by denitrifying PAOs (DNPAOs) was achieved in the A(2)/O reactor with [Formula: see text] as the electron acceptor from the BCO reactor. Long term operational tests (600 days) were conducted with various operational parameters [e.g., hydraulic retention time (HRTs), nitrate recycling ratio (Rs), volume ratio (Vs)] to examine the denitrifying phosphorus removal performance. The system exhibited the highest removal of TN and [Formula: see text] at the HRTs of 8 h, Rs of 300% and Vs of 2:4:1. The optimal TN and [Formula: see text] removals were 80.30% and 96.61% at low COD/TN of 3.21. The species diversity and microbial community examined by the Illumina MiSeq method demonstrated the fact of two-sludge system, and the improved community structure by long-term optimization was prominent comparing with the seed sludge. Additionally, Accumulibacter and Dechloromonas were the dominant functional PAOs with 25.74% in the A(2)/O reactor, while nitrifiers (including Nitrosomonas and Nitrospira) were gradually enriched with 13.10%, 21.33%, and 31.10% in the three stages of the BCO reactor.

  14. Heterologous expression of the yeast HAL5 gene in tomato enhances salt tolerance by reducing shoot Na+ accumulation in the long term.

    PubMed

    García-Abellan, Jose O; Egea, Isabel; Pineda, Benito; Sanchez-Bel, Paloma; Belver, Andres; Garcia-Sogo, Begoña; Flores, Francisco B; Atares, Alejandro; Moreno, Vicente; Bolarin, Maria C

    2014-12-01

    For salt tolerance to be achieved in the long-term plants must regulate Na(+)/K(+) homeostasis over time. In this study, we show that the salt tolerance induced by overexpression of the yeast HAL5 gene in tomato (Solanum lycopersicum) was related to a lower leaf Na(+) accumulation in the long term, by reducing Na(+) transport from root to shoot over time regardless of the severity of salt stress. Furthermore, maintaining Na(+)/K(+) homeostasis over time was associated with changes in the transcript levels of the Na(+) and K(+) transporters such as SlHKT1;2 and SlHAK5. The expression of SlHKT1;2 was upregulated in response to salinity in roots of transgenic plants but downregulated in the roots of wild-type (WT) plants, which seems to be related to the lower Na(+) transport rate from root to shoot in transgenic plants. The expression of the SlHAK5 increased in roots and leaves of both WT and transgenic plants under salinity. However, this increase was much higher in the leaves of transgenic plants than in those of WT plants, which may be associated with the ability of transgenic leaves to maintain Na(+)/K(+) homeostasis over time. Taken together, the results show that the salt tolerance mechanism induced by HAL5 overexpression in tomato is related to the appropriate regulation of ion transport from root to shoot and maintenance of the leaf Na(+)/K(+) homeostasis through modulation of SlHKT1 and SlHAK5 over time.

  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. Re-imagining long-term services and supports: towards livable environments, service capacity, and enhanced community integration, choice, and quality of life for seniors.

    PubMed

    Kane, Rosalie A; Cutler, Lois J

    2015-04-01

    In the half century since enactment of the 1965 Great Society programs, accomplishments were gradually made to improve access to and quality of long-term services and supports (LTSS), including: mitigation of financial and care abuses in nursing facilities (NFs); substantial rebalancing of LTSS towards consumer-preferred home-and-community-based services (HCBS); increasing flexible consumer-centered HCBS including payment to family caregivers; and more assisted-living and housing options for seniors with heavy care needs. A unified planning and advocacy agenda across age and disability type and greater consumer transparency fueled progress. Nonetheless, LTSS is a broken system; persistent problems interfere with substantial and necessary change. These include; over-emphasis on safety for LTSS consumers; inattention to physical environments in all settings; regulatory and professional rigidity; and poor communication and information. Our recommendations are aimed at builders and designers, LTSS professionals, regulators, and educators/trainers; the last may be crucial in forging new consensus and over-coming entrenched beliefs. Policy recommendations include relatively narrow steps-for example, requiring single occupancy in all NFs and assisted living settings financed with public dollars-to broad reworking of the prerequisites for livable age-friendly (and dementia-friendly) communities and for a capable, flexible LTSS workforce.

  17. Long-term treatment with a phosphodiesterase type 5 inhibitor improves pulmonary hypertension secondary to heart failure through enhancing the natriuretic peptides-cGMP pathway.

    PubMed

    Yamamoto, Takashi; Wada, Atsuyuki; Tsutamoto, Takayoshi; Ohnishi, Masato; Horie, Minoru

    2004-11-01

    In advanced heart failure (HF), the compensatory pulmonary vasodilation is attenuated due to the relative insufficiency of cGMP despite increased secretion of natriuretic peptides (NPs). Phosphodiesterase type 5 (PDE5) inhibitors prevent cGMP degradation, and thus may potentiate the effect of the NPs-cGMP pathway. We orally administered a specific PDE5 inhibitor, T-1032 (1 mg/kg; twice a day, n = 7) or placebo (n = 7) for 2 weeks in dogs with HF induced by rapid pacing (270 bpm, 3 weeks) and examined the plasma levels of atrial natriuretic peptide (ANP), cGMP, and hemodynamic parameters. We also examined the hemodynamic changes after injection of a specific NPs receptor antagonist, HS-142-1 (3 mg/kg), under treatment with T-1032. T-1032 significantly increased plasma cGMP levels compared with the vehicle group despite low plasma ANP levels associated with improvement in cardiopulmonary hemodynamics. HS-142-1 significantly decreased plasma cGMP levels in both groups, whereas it did not change all hemodynamic parameters in the vehicle group. In contrast, in the T-1032 group, HS-142-1 significantly increased pulmonary arterial pressure and pulmonary vascular resistance. These results indicated that long-term treatment with a PDE5 inhibitor improved pulmonary hypertension secondary to HF and the NPs-cGMP pathway contributed to this therapeutic effect.

  18. Slice orientation and muscarinic acetylcholine receptor activation determine the involvement of N-methyl D-aspartate receptor subunit GluN2B in hippocampal area CA1 long-term depression

    PubMed Central

    2011-01-01

    Background The contribution of different GluN2 subunits of the N-methyl D-aspartate (NMDA) receptor to the induction of bidirectional hippocampal synaptic plasticity is a controversial topic. As both supporting and refuting evidence for the hypothesis of subunit specialization in opposing directions of plasticity has accumulated since it was first proposed a few years ago, we hypothesize that differences in experimental conditions may have in part contributed to some of the inconsistent results from these studies. Here we investigate the controversial hypothesis that long-term depression (LTD) is preferentially induced by GluN2B-containing NMDA receptors in area CA1 of hippocampal slices. Results We find that brain slices from 2-3 week old rats prepared in the sagittal orientation have GluN2B-independent LTD whereas slices prepared in the coronal orientation have GluN2B-dependent LTD. There was no difference between the orientations in the fraction of the NMDAR EPSC sensitive to a GluN2B-selective antagonist, leading us to believe that the intracellular signaling properties of the NMDARs were different in the two preparations. Coronal slices had greater association of LTD-related intracellular signaling protein RasGRF1 with GluN2B relative to sagittal slices. Antagonism of muscarinic acetylcholine receptors (mAChRs) in the sagittal slices returned LTD to a GluN2B-dependent form and increased the association of GluN2B with RasGRF1. Conclusions These results suggest a novel form of NMDAR modulation by mAChRs and clarify some disagreement in the literature. PMID:22082088

  19. Deletion of Kv4.2 gene eliminates dendritic A-type K+ current and enhances induction of long-term potentiation in hippocampal CA1 pyramidal neurons.

    PubMed

    Chen, Xixi; Yuan, Li-Lian; Zhao, Cuiping; Birnbaum, Shari G; Frick, Andreas; Jung, Wonil E; Schwarz, Thomas L; Sweatt, J David; Johnston, Daniel

    2006-11-22

    Dendritic, backpropagating action potentials (bAPs) facilitate the induction of Hebbian long-term potentiation (LTP). Although bAPs in distal dendrites of hippocampal CA1 pyramidal neurons are attenuated when propagating from the soma, their amplitude can be increased greatly via downregulation of dendritic A-type K+ currents. The channels that underlie these currents thus may represent a key regulatory component of the signaling pathways that lead to synaptic plasticity. We directly tested this hypothesis by using Kv4.2 knock-out mice. Deletion of the Kv4.2 gene and a loss of Kv4.2 protein resulted in a specific and near-complete elimination of A-type K+ currents from the apical dendrites of CA1 pyramidal neurons. The absence of dendritic Kv4.2-encoded A-type K+ currents led to an increase of bAP amplitude and an increase of concurrent Ca2+ influx. Furthermore, CA1 pyramidal neurons lacking dendritic A-type K+ currents from Kv4.2 knock-out mice exhibited a lower threshold than those of wild-type littermates for LTP induction with the use of a theta burst pairing protocol. LTP triggered with the use of a saturating protocol, on the other hand, remained indistinguishable between Kv4.2 knock-out and wild-type neurons. Our results support the hypothesis that dendritic A-type K+ channels, composed of Kv4.2 subunits, regulate action potential backpropagation and the induction of specific forms of synaptic plasticity.

  20. Long-term intermittent multiple micronutrient supplementation enhances hemoglobin and micronutrient status more than iron + folic acid supplementation in Bangladeshi rural adolescent girls with nutritional anemia.

    PubMed

    Ahmed, Faruk; Khan, Moududur R; Akhtaruzzaman, Mohammad; Karim, Rezaul; Williams, Gail; Torlesse, Harriet; Darnton-Hill, Ian; Dalmiya, Nita; Banu, Cadi P; Nahar, Badrun

    2010-10-01

    Previous short-term supplementation studies showed no additional hematologic benefit of multiple micronutrients (MMN) compared with iron + folic acid (IFA) in adolescent girls. This study examines whether long-term once- or twice-weekly supplementation of MMN can improve hemoglobin (Hb) and micronutrient status more than twice-weekly IFA supplementation in anemic adolescent girls in Bangladesh. Anemic girls (n = 324) aged 11-17 y attending rural schools were given once- or twice-weekly MMN or twice-weekly IFA, containing 60 mg iron/dose in both supplements, for 52 wk in a randomized double-blind trial. Blood samples were collected at baseline and 26 and 52 wk. Intent to treat analysis showed no significant difference in the Hb concentration between treatments at either 26 or 52 wk. However, after excluding girls with hemoglobinopathy and adjustment for baseline Hb, a greater increase in Hb was observed with twice-weekly MMN at 26 wk (P = 0.045). Although all 3 treatments effectively reduced iron deficiency, once-weekly MMN produced significantly lower serum ferritin concentrations than the other treatments at both 26 and 52 wk. Both once- and twice-weekly MMN significantly improved riboflavin, vitamin A, and vitamin C status compared with IFA. Overall, once-weekly MMN was less efficacious than twice-weekly MMN in improving iron, riboflavin, RBC folic acid, and vitamin A levels. Micronutrient supplementation beyond 26 wk was likely important in sustaining improved micronutrient status. These findings highlight the potential usefulness of MMN intervention in this population and have implications for programming.

  1. Protecting the Health of Astronauts: Enhancing Occupational Health Monitoring and Surveillance for Former NASA Astronauts to Understand Long-Term Outcomes of Spaceflight-Related Exposures

    NASA Technical Reports Server (NTRS)

    Rossi, Meredith; Lee, Lesley; Wear, Mary; Van Baalen, Mary; Rhodes, Bradley

    2017-01-01

    The astronaut community is unique, and may be disproportionately exposed to occupational hazards not commonly seen in other communities. The extent to which the demands of the astronaut occupation and exposure to spaceflight-related hazards affect the health of the astronaut population over the life course is not completely known. A better understanding of the individual, population, and mission impacts of astronaut occupational exposures is critical to providing clinical care, targeting occupational surveillance efforts, and planning for future space exploration. The ability to characterize the risk of latent health conditions is a significant component of this understanding. Provision of health screening services to active and former astronauts ensures individual, mission, and community health and safety. Currently, the NASA-Johnson Space Center (JSC) Flight Medicine Clinic (FMC) provides extensive medical monitoring to active astronauts throughout their careers. Upon retirement, astronauts may voluntarily return to the JSC FMC for an annual preventive exam. However, current retiree monitoring includes only selected screening tests, representing an opportunity for augmentation. The potential long-term health effects of spaceflight demand an expanded framework of testing for former astronauts. The need is two-fold: screening tests widely recommended for other aging populations are necessary to rule out conditions resulting from the natural aging process (e.g., colonoscopy, mammography); and expanded monitoring will increase NASA's ability to better characterize conditions resulting from astronaut occupational exposures. To meet this need, NASA has begun an extensive exploration of the overall approach, cost, and policy implications of e an Astronaut Occupational Health program to include expanded medical monitoring of former NASA astronauts. Increasing the breadth of monitoring services will ultimately enrich the existing evidence base of occupational health risks

  2. Long-term estrogen exposure promotes carcinogen bioactivation, induces persistent changes in gene expression, and enhances the tumorigenicity of MCF-7 human breast cancer cells

    SciTech Connect

    Spink, Barbara C.; Bennett, James A.; Pentecost, Brian T.; Lostritto, Nicole; Englert, Neal A.; Benn, Geoffrey K.; Goodenough, Angela K.; Turesky, Robert J.; Spink, David C.

    2009-11-01

    The cumulative exposure to estrogens is an important determinant in the risk of breast cancer, yet the full range of mechanisms involving estrogens in the genesis and progression of breast cancer remains a subject of debate. Interactions of estrogens and environmental toxicants have received attention as putative factors contributing to carcinogenesis. Mechanistic studies have demonstrated interactions between estrogen receptor alpha (ERalpha) and the aryl hydrocarbon receptor (AhR), with consequences on the genes that they regulate. Many studies of ERalpha and AhR-mediated effects and crosstalk between them have focused on the initial molecular events. In this study, we investigated ERalpha- and AhR-mediated effects in long-term estrogen exposed (LTEE) MCF-7 human breast cancer cells, which were obtained by continuous culturing for at least 12 weeks in medium supplemented with 1 nM of 17beta-estradiol (E{sub 2}). With these LTEE cells and with parallel control cells cultured without E{sub 2} supplementation, we performed an extensive study of cytochrome P450 (CYP) induction, carcinogen bioactivation, global gene expression, and tumorigenicity in immunocompromised mice. We found that LTEE cells, in comparison with control cells, had higher levels of AhR mRNA and protein, greater responsiveness for AhR-regulated CYP1A1 and CYP1B1 induction, a 6-fold higher initial level of benzo(a)pyrene-DNA adducts as determined by liquid chromatography tandem mass spectrometry, marked differences in the expression of numerous genes, and a higher rate of E{sub 2}-dependent tumor growth as xenografts. These studies indicate that LTEE causes adaptive responses in MCF-7 cells, which may reflect processes that contribute to the overall carcinogenic effect of E{sub 2}.

  3. Long-term estrogen exposure promotes carcinogen bioactivation, induces persistent changes in gene expression, and enhances the tumorigenicity of MCF-7 human breast cancer cells

    PubMed Central

    Spink, Barbara C.; Bennett, James A.; Pentecost, Brian T.; Lostritto, Nicole; Englert, Neal A.; Benn, Geoffrey K.; Goodenough, Angela K.; Turesky, Robert J.; Spink, David C.

    2009-01-01

    The cumulative exposure to estrogens is an important determinant in the risk of breast cancer, yet the full range of mechanisms involving estrogens in the genesis and progression of breast cancer remains a subject of debate. Interactions of estrogens and environmental toxicants have received attention as putative factors contributing to carcinogenesis. Mechanistic studies have demonstrated interactions between estrogen receptor α (ERα) and the aryl hydrocarbon receptor (AhR), with consequences on the genes that they regulate. Many studies of ERα and AhR-mediated effects and crosstalk between them have focused on the initial molecular events. In this study, we investigated ERα- and AhR-mediated effects in long-term estrogen exposed (LTEE) MCF-7 human breast cancer cells, which were obtained by continuous culturing for at least 12 weeks in medium supplemented with 1 nM of 17β-estradiol (E2). With these LTEE cells and with parallel control cells cultured without E2 supplementation, we performed an extensive study of cytochrome P450 (CYP) induction, carcinogen bioactivation, global gene expression, and tumorigenicity in immunocompromised mice. We found that LTEE cells, in comparison with control cells, had higher levels of AhR mRNA and protein, greater responsiveness for AhR-regulated CYP1A1 and CYP1B1 induction, a 6-fold higher initial level of benzo(a)pyrene-DNA adducts as determined by liquid chromatography tandem mass spectrometry, marked differences in the expression of numerous genes, and a higher rate of E2-dependent tumor growth as xenografts. These studies indicate that LTEE causes adaptive responses in MCF-7 cells, which may reflect processes that contribute to the overall carcinogenic effect of E2. PMID:19619570

  4. Arbuscular mycorrhizal fungus enhances P acquisition of wheat (Triticum aestivum L.) in a sandy loam soil with long-term inorganic fertilization regime.

    PubMed

    Hu, Junli; Lin, Xiangui; Wang, Junhua; Cui, Xiangchao; Dai, Jue; Chu, Haiyan; Zhang, Jiabao

    2010-10-01

    The P efficiency, crop yield, and response of wheat to arbuscular mycorrhizal fungus (AMF) Glomus caledonium were tested in an experimental field with long-term (19 years) fertilizer management. The experiment included five fertilizer treatments: organic amendment (OA), half organic amendment plus half mineral fertilizer (1/2 OM), mineral fertilizer NPK, mineral fertilizer NK, and the control (without fertilization). AMF inoculation responsiveness (MIR) of wheat plants at acquiring P were estimated by comparing plants grown in unsterilized soil inoculated with G. caledonium and in untreated soil containing indigenous AMF. Without AMF inoculation, higher crop yields but lower colonization rates were observed in the NPK and two OA-inputted treatments, and NPK had significantly (P < 0.05) lower impacts on organic C and available P in soils and thereby P acquisition of wheat plants compared with OA and 1/2 OM. G. caledonium inoculation significantly (P < 0.05) increased colonization rates with the NPK and two P-deficient treatments but significantly (P < 0.05) increased vegetative biomass, crop yield, and P acquisition of wheat as well as soil alkaline phosphatase (ALP) activity, only with the NPK treatment. This gave an MIR of ca. 45% on total P acquisition of wheat plants. There were no other remarkable MIRs. It suggested that the MIR is determined by soil available P status, and rational combination of AMF with chemical NPK fertilizer can compensate for organic amendments by improving P-acquisition efficiency in arable soils.

  5. Impaired Long-term Potentiation and Enhanced Neuronal Excitability in the Amygdala of CaV1.3 Knockout Mice

    PubMed Central

    McKinney, Brandon C.; Sze, Wilson; Lee, Benjamin; Murphy, Geoffrey G.

    2009-01-01

    Previously, we demonstrated that mice in which the gene for the L-type voltage-gated calcium channel CaV1.3 is deleted (CaV1.3 knockout mice) exhibit an impaired ability to consolidate contextually-conditioned fear. Given that this form of Pavlovian fear conditioning is critically dependent on the basolateral complex of the amygdala (BLA), we were interested in the mechanisms by which CaV1.3 contributes to BLA neurophysiology. In the present study, we used in vitro amygdala slices prepared from CaV1.3 knockout mice and wild-type littermates to explore the role of CaV1.3 in long-term potentiation (LTP) and intrinsic neuronal excitability in the BLA. We found that LTP in the lateral nucleus (LA) of the BLA, induced by high-frequency stimulation of the external capsule, was significantly reduced in CaV1.3 knockout mice. Additionally, we found that BLA principal neurons from CaV1.3 knockout mice were hyperexcitable, exhibiting significant increases in firing rates and decreased interspike intervals in response to prolonged somatic depolarization. This aberrant increase in neuronal excitability appears to be at least in part due to a concomitant reduction in the slow component of the post-burst afterhyperpolarization. Together, these results demonstrate altered neuronal function in the BLA of CaV1.3 knockout mice which may account for the impaired ability of these mice to consolidate contextually-conditioned fear. PMID:19595780

  6. Co-infection of Long-Term Carriers of Plasmodium falciparum with Schistosoma haematobium Enhances Protection from Febrile Malaria: A Prospective Cohort Study in Mali

    PubMed Central

    Sangala, Jules; Li, Shanping; Doumtabe, Didier; Kone, Younoussou; Traoré, Abdrahamane; Bathily, Aboudramane; Sogoba, Nafomon; Coulibaly, Michel E.; Huang, Chiung-Yu; Ongoiba, Aissata; Kayentao, Kassoum; Diallo, Mouctar; Dramane, Zongo; Nutman, Thomas B.; Crompton, Peter D.; Doumbo, Ogobara; Traore, Boubacar

    2014-01-01

    Background Malaria and schistosomiasis often overlap in tropical and subtropical countries and impose tremendous disease burdens; however, the extent to which schistosomiasis modifies the risk of febrile malaria remains unclear. Methods We evaluated the effect of baseline S. haematobium mono-infection, baseline P. falciparum mono-infection, and co-infection with both parasites on the risk of febrile malaria in a prospective cohort study of 616 children and adults living in Kalifabougou, Mali. Individuals with S. haematobium were treated with praziquantel within 6 weeks of enrollment. Malaria episodes were detected by weekly physical examination and self-referral for 7 months. The primary outcome was time to first or only malaria episode defined as fever (≥37.5°C) and parasitemia (≥2500 asexual parasites/µl). Secondary definitions of malaria using different parasite densities were also explored. Results After adjusting for age, anemia status, sickle cell trait, distance from home to river, residence within a cluster of high S. haematobium transmission, and housing type, baseline P. falciparum mono-infection (n = 254) and co-infection (n = 39) were significantly associated with protection from febrile malaria by Cox regression (hazard ratios 0.71 and 0.44; P = 0.01 and 0.02; reference group: uninfected at baseline). Baseline S. haematobium mono-infection (n = 23) did not associate with malaria protection in the adjusted analysis, but this may be due to lack of statistical power. Anemia significantly interacted with co-infection (P = 0.009), and the malaria-protective effect of co-infection was strongest in non-anemic individuals. Co-infection was an independent negative predictor of lower parasite density at the first febrile malaria episode. Conclusions Co-infection with S. haematobium and P. falciparum is significantly associated with reduced risk of febrile malaria in long-term asymptomatic carriers of P. falciparum. Future studies are

  7. Potential of N-acetylated-para-aminosalicylic Acid to Accelerate Manganese Enhancement Decline for Long-term MEMRI in Rodent Brain

    PubMed Central

    Bade, Aditya N; Zhou, Biyun; McMillan, JoEllyn; Narayanasamy, Prabagaran; Veerubhotla, Ram; Gendelman, Howard E; Boska, Michael D; Liu, Yutong

    2015-01-01

    Background Manganese (Mn2+)-enhanced MRI (MEMRI) is a valuable imaging tool to study brain structure and function in normal and diseased small animals. The brain retention of Mn2+ is relatively long with a half-life (t1/2) of 51 to 74 days causing a slow decline of MRI signal enhancement following Mn2+ administration. Such slow decline limits using repeated MEMRI to follow the central nervous system longitudinally in weeks or months. This is because residual Mn2+ from preceding administrations can confound the interpretation of imaging results. We investigated whether the Mn2+ enhancement decline could be accelerated thus enabling repeated MEMRI, and as a consequence broadens the utility of MEMRI tests. New Methods We investigated whether N-acetyl-para-aminosalicylic acid (AcPAS), a chelator of Mn2+, could affect the decline of Mn2+ induced MRI enhancement in brain. Results and Conclusion Two-week treatment with AcPAS (200 mg/kg/dose × 3 daily) accelerated the decline of Mn2+ induced enhancement in MRI. In the whole brain on average the enhancement declined from 100% to 17% in AcPAS treated mice, while in PBS controls the decline is from 100% to 27%. We posit that AcPAS could enhance MEMRI utility for evaluating brain biology in small animals. Comparison with Existing Methods To the best of our knowledge, no method exists to accelerate the decline of the Mn2+ induced MRI enhancement for repeated MEMRI tests. PMID:26004847

  8. Depressed mood enhances anxiety to unpredictable threat

    PubMed Central

    Robinson, OJ; Overstreet, C; Letkiewicz, A; Grillon, C

    2011-01-01

    Background Depression and anxiety disorders (AD) are highly comorbid, but the reason for this comorbidity is unclear. One possibility is that they predispose one another. An informative way to examine interactions between disorders without the confounds present in patient populations is to manipulate the psychological processes thought to underlie the pathological states in healthy individuals. In this paper we therefore asked whether a model of the sad mood in depression can enhance psychophysiological responses (startle) to a model of the anxiety in AD. We predicted that sad mood would increase anxious anxiety-potentiated startle responses. Methods In a between-subjects design, participants (N=36) completed either a sad mood induction procedure (N=18) or neutral mood induction procedure (N=18). Startle responses were assessed during short duration predictable electric shock conditions (fear-potentiated startle) or long-duration unpredictable threat of shock conditions (anxiety-potentiated startle). Results Induced sadness enhanced anxiety-, but not fear- potentiated startle. Conclusions This study provides support for the hypothesis that sadness can increase anxious responding measured by the affective startle response. This, taken together with prior evidence that AD can contribute to depression, provides initial experimental support for the proposition that AD and depression are frequently comorbid because they may be mutually reinforcing. PMID:22088577

  9. A descriptive inquiry of the definitions of critical thinking and enhancers and barriers reported by nurses working in long-term care facilities.

    PubMed

    Raterink, Ginger

    2008-09-01

    Critical thinking has been an outcome of nursing education since the 1980s. There remains a lack of agreement on definitions, methods of teaching, and methods of evaluation among practicing nurses. This study asked practicing nurses to define critical thinking. It also asked nurses to describe what work-related factors enhanced or posed barriers to the use of critical thinking in practice. Elements of the definitions presented were found to be consistent with current nursing definitions of critical thinking. Enhancers and barriers overlapped and were found to be consistent among the nurses at all facilities studied, with implications for continuing education and staff development.

  10. Suicidal Behavior in Long-Term Care Facilities.

    ERIC Educational Resources Information Center

    Osgood, Nancy J.; Brant, Barbara A.

    1990-01-01

    Surveyed administrators of 463 long-term care facilities concerning overt suicides and intentional life-threatening behaviors. Data revealed that White males were highest risk group. Refusal to eat, drink, or take medications were most common suicidal behaviors. Depression, loneliness, feelings of family rejection, and loss were significant…

  11. Zinc Supplementation Enhances Hepatic Regeneration by Preserving Hepatocyte Nuclear Factor-4α in Mice Subjected to Long-Term Ethanol Administration

    PubMed Central

    Kang, Xinqin; Song, Zhenyuan; McClain, Craig J.; Kang, Y. James; Zhou, Zhanxiang

    2008-01-01

    Alcoholic liver disease is associated with sustained liver damage and impaired regeneration, as well as significant zinc deficiency. This study was undertaken to examine whether dietary zinc supplementation could improve liver regeneration by increasing the expression of genes involved in hepatic cellular proliferation in a mouse model of alcoholic liver disease. Adult 129S6 mice fed an ethanol-containing liquid diet for 6 months developed alcoholic liver disease as measured by serum alanine transferase activity and histopathological changes. Zinc supplementation to ethanol-exposed mice enhanced liver regeneration as indicated by increased numbers of proliferation cell nuclear antigen (PCNA)-positive and bromodeoxyuridine (BrdU)-labeled hepatocytes. Zinc-enhanced liver regeneration was associated with an increase in hepatocyte nuclear factor-4α (HNF-4α), a liver-enriched, zinc-finger transcription factor. Studies using cultured HepG2 cells showed that zinc deficiency suppressed cell proliferation and cell proliferation-related proteins, including hepatocyte growth factor (HGF), insulin-like growth factor I (IGF-I), insulin-like growth factor binding protein 1 (IGFBP1), metallothionein (MT), and cyclin D1, as well as HNF-4α. HNF-4α gene silencing inhibited cell proliferation in association with decreased protein levels of IGF-I, IGFBP1, MT, and cyclin D1. The present study provides evidence that zinc supplementation enhances liver regeneration at least in part by HNF-4α through the up-regulation of cell proliferation-related proteins, suggesting that dietary zinc supplementation may have beneficial effects in alcoholic liver disease. PMID:18349129

  12. 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

  13. Asthma Medicines: Long-Term Control

    MedlinePlus

    ... Size Email Print Share Asthma Medicines: Long-term Control Page Content Article Body Corticosteroids Synthetic versions of ... form, they are used exclusively for long-term control; they are not very effective for acute symptoms. ...

  14. Enhanced long-term ammonium removal and its ranked contribution of microbial genes associated with nitrogen cycling in a lab-scale multimedia biofilter.

    PubMed

    Wang, Honglei; Ji, Guodong; Bai, Xueyuan

    2015-11-01

    The multimedia biofilter achieved high and stable removal efficiencies for chemical oxygen demand (COD, 62-98%) and NH4(+) (68-98%) without costly aeration. Results revealed that lower CL (less than 13.9gCOD/m(3)d) and ACL (less than 2.8gNH4(+)-N/m(3)d) or a C/N ratio exceeding five was required to reduce NO3(-)-N accumulation and NO/N2O emission. Integrated analyses indicated that the coupling of simultaneous nitrification, anammox and denitrification processes (SNAD) were the primary reason accounted for the enhanced NH4(+)-N treatment performance. NH4(+)-N removal pathways can be ranked as follows: nitrification (amoA, archaeal) (54.6%)>partial denitrification (nirS, nirK) and anammox (37.8%)>anammox and partial denitrification (narG, napA) (12.6%). Specifically, NH4(+)-N removal was significantly inhibited by NO2(-)-N accumulation in the system (-21.6% inhibition). Results from stepwise regression analysis suggested that the NH4(+) removal rate was collectively controlled by amoA, archaeal, anammox, nirS, nirK, narG and napA.

  15. Long-term feeding of hydroalcoholic extract powder of Lepidium meyenii (maca) enhances the steroidogenic ability of Leydig cells to alleviate its decline with ageing in male rats.

    PubMed

    Yoshida, K; Ohta, Y; Kawate, N; Takahashi, M; Inaba, T; Hatoya, S; Morii, H; Takahashi, K; Ito, M; Tamada, H

    2017-03-10

    This study examined whether feeding hydroalcoholic extract of Lepidium meyenii (maca) to 8-week-old (sexually maturing) or 18-week-old (mature) male rats for more than a half year affects serum testosterone concentration and testosterone production by Leydig cells cultured with hCG, 22R-hydroxycholesterol or pregnenolone. Testosterone concentration was determined in the serum samples obtained before and 6, 12, 18 and 24 weeks after the feeding, and it was significantly increased only at the 6 weeks in the group fed with the maca extract to maturing rats when it was compared with controls. Testosterone production by Leydig cells significantly increased when cultured with hCG by feeding the maca extract to maturing rats for 27 weeks (35 weeks of age) and when cultured with 22R-hydroxycholesterol by feeding it to mature rats for 30 weeks (48 weeks of age). Overall testosterone production by cultured Leydig cells decreased to about a half from 35 to 48 weeks of age. These results suggest that feeding the maca extract for a long time to male rats may enhance the steroidogenic ability of Leydig cells to alleviate its decline with ageing, whereas it may cause only a transient increase in blood testosterone concentration in sexually maturing male rats.

  16. Enhancement of regulatory T cell-like suppressive function in MT-2 by long-term and low-dose exposure to asbestos.

    PubMed

    Ying, Chen; Maeda, Megumi; Nishimura, Yasumitsu; Kumagai-Takei, Naoko; Hayashi, Hiroaki; Matsuzaki, Hidenori; Lee, Suni; Yoshitome, Kei; Yamamoto, Shoko; Hatayama, Tamayo; Otsuki, Takemi

    2015-12-02

    Asbestos exposure causes lung fibrosis and various malignant tumors such as lung cancer and malignant mesothelioma. The effects of asbestos on immune cells have not been thoroughly investigated, although our previous reports showed that asbestos exposure reduced anti-tumor immunity. The effects of continuous exposure of regulatory T cells (Treg) to asbestos were examined using the HTLV-1 immortalized human T cell line MT-2, which possesses a suppressive function and expresses the Treg marker protein, Foxp3. Sublines were generated by the continuous exposure to low doses of asbestos fibers for more than one year. The sublines exposed to asbestos showed enhanced suppressive Treg function via cell-cell contact, and increased production of soluble factors such as IL-10 and transforming growth factor (TGF)-β1. These results also indicated that asbestos exposure induced the reduction of anti-tumor immunity, and efforts to develop substances to reverse this reduction may be helpful in preventing the occurrence of asbestos-induced tumors.

  17. 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.

  18. AB055. Long term NIV

    PubMed Central

    Siopi, Dimitra

    2016-01-01

    During the last decades, non-invasive mechanical ventilation has evolved into one of the most evidence-based areas of respiratory medicine, with many indications in acute or chronic respiratory failure. From the first application of negative pressure models during poliomyelitis epidemics to the new sophisticated positive pressure models, and the development of the “intelligent ventilators”, there has been a long time course. Undoubtedly the spur was given by better understanding of respiratory physiology during sleep and the shift of healthcare towards a chronic base. Novel randomized controlled trials (RCTs) established the use of NIV in acute respiratory failure due to exacerbations of COPD, as well as acute pulmonary edema and weaning from invasive mechanical ventilation. Long-term NIV has been used in neuromuscular diseases for many decades, first in Duchenne muscular dystrophy, and then spreading to other disorders of this category, increasing survival in inherited neuromuscular diseases. NIV should be initiated early in the course of the disease, when symptomatic nocturnal hypoventilation is detected. Combined with cough augmentation (physiotherapy, insufflation-exsufflation devices) and percutaneous gastrostomy feeding, it can delay tracheostomy and invasive ventilation. In ALS patients NIV improves the quality of life and increases survival, especially when there is no bulbar involvement. The right time to initiate ventilation in this group of patients is not well established since it is difficult to detect signs and symptom of respiratory impairment. Patients seem to benefit from an early application of NIV, and their personal decisions should always be considered before any intervention. In patients with chest wall disorders NIV—despite the fact that RCTs are lacking—has proved its value in many uncontrolled trials and numerous reports. It seems to improve the work of breathing, sleep architecture, nocturnal and daytime arterial blood gases. The

  19. 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…

  20. Long Term TOA - M Data and Information

    Atmospheric Science Data Center

    2015-06-30

    A Long-Term TOA and Constrained Surface Radiation Budget Project A Long-Term TOA and Constrained Surface Readiation Budget Dataset Using Merged CERES, ... and apply the knowledge to existing data to develop long-term (nearly 30 years) consistent and calibrated data product (TOA irradiances ...

  1. Presynaptic Protein Synthesis Is Required for Long-Term Plasticity of GABA Release.

    PubMed

    Younts, Thomas J; Monday, Hannah R; Dudok, Barna; Klein, Matthew E; Jordan, Bryen A; Katona, István; Castillo, Pablo E

    2016-10-19

    Long-term changes of neurotransmitter release are critical for proper brain function. However, the molecular mechanisms underlying these changes are poorly understood. While protein synthesis is crucial for the consolidation of postsynaptic plasticity, whether and how protein synthesis regulates presynaptic plasticity in the mature mammalian brain remain unclear. Here, using paired whole-cell recordings in rodent hippocampal slices, we report that presynaptic protein synthesis is required for long-term, but not short-term, plasticity of GABA release from type 1 cannabinoid receptor (CB1)-expressing axons. This long-term depression of inhibitory transmission (iLTD) involves cap-dependent protein synthesis in presynaptic interneuron axons, but not somata. Translation is required during the induction, but not maintenance, of iLTD. Mechanistically, CB1 activation enhances protein synthesis via the mTOR pathway. Furthermore, using super-resolution STORM microscopy, we revealed eukaryotic ribosomes in CB1-expressing axon terminals. These findings suggest that presynaptic local protein synthesis controls neurotransmitter release during long-term plasticity in the mature mammalian brain.

  2. Long term perfusion system supporting adipogenesis

    PubMed Central

    Abbott, Rosalyn D.; Raja, Waseem K.; Wang, Rebecca Y.; Stinson, Jordan A.; Glettig, Dean L.; Burke, Kelly A.; Kaplan, David L.

    2015-01-01

    Adipose tissue engineered models are needed to enhance our understanding of disease mechanisms and for soft tissue regenerative strategies. Perfusion systems generate more physiologically relevant and sustainable adipose tissue models, however adipocytes have unique properties that make culturing them in a perfusion environment challenging. In this paper we describe the methods involved in the development of two perfusion culture systems (2D and 3D) to test their applicability for long term in vitro adipogenic cultures. It was hypothesized that a silk protein biomaterial scaffold would provide a 3D framework, in combination with perfusion flow, to generate a more physiologically relevant sustainable adipose tissue engineered model than 2D cell culture. Consistent with other studies evaluating 2D and 3D culture systems for adipogenesis we found that both systems successfully model adipogensis, however 3D culture systems were more robust, providing the mechanical structure required to contain the large, fragile adipocytes that were lost in 2D perfused culture systems. 3D perfusion also stimulated greater lipogenesis and lipolysis and resulted in decreased secretion of LDH compared to 2D perfusion. Regardless of culture configuration (2D or 3D) greater glycerol was secreted with the increased nutritional supply provided by perfusion of fresh media. These results are promising for adipose tissue engineering applications including long term cultures for studying disease mechanisms and regenerative approaches, where both acute (days to weeks) and chronic (weeks to months) cultivation are critical for useful insight. PMID:25843606

  3. Clinical review: Long-term noninvasive ventilation

    PubMed Central

    Robert, Dominique; Argaud, Laurent

    2007-01-01

    Noninvasive positive ventilation has undergone a remarkable evolution over the past decades and is assuming an important role in the management of both acute and chronic respiratory failure. Long-term ventilatory support should be considered a standard of care to treat selected patients following an intensive care unit (ICU) stay. In this setting, appropriate use of noninvasive ventilation can be expected to improve patient outcomes, reduce ICU admission, enhance patient comfort, and increase the efficiency of health care resource utilization. Current literature indicates that noninvasive ventilation improves and stabilizes the clinical course of many patients with chronic ventilatory failure. Noninvasive ventilation also permits long-term mechanical ventilation to be an acceptable option for patients who otherwise would not have been treated if tracheostomy were the only alternative. Nevertheless, these results appear to be better in patients with neuromuscular/-parietal disorders than in chronic obstructive pulmonary disease. This clinical review will address the use of noninvasive ventilation (not including continuous positive airway pressure) mainly in diseases responsible for chronic hypoventilation (that is, restrictive disorders, including neuromuscular disease and lung disease) and incidentally in others such as obstructive sleep apnea or problems of central drive. PMID:17419882

  4. Genetics of long-term treatment outcome in bipolar disorder.

    PubMed

    Fabbri, Chiara; Serretti, Alessandro

    2016-02-04

    Bipolar disorder (BD) shows one of the strongest genetic predispositions among psychiatric disorders and the identification of reliable genetic predictors of treatment response could significantly improve the prognosis of the disease. The present study investigated genetic predictors of long-term treatment-outcome in 723 patients with BD type I from the STEP-BD (Systematic Treatment Enhancement Program for Bipolar Disorder) genome-wide dataset. BD I patients with >6months of follow-up and without any treatment restriction (reflecting a natural setting scenario) were included. Phenotypes were the total and depressive episode rates and the occurrence of one or more (hypo)manic/mixed episodes during follow-up. Quality control of genome-wide data was performed according to standard criteria and linear/logistic regression models were used as appropriate under an additive hypothesis. Top genes were further analyzed through a pathway analysis. Genes previously involved in the susceptibility to BD (DFNB31, SORCS2, NRXN1, CNTNAP2, GRIN2A, GRM4, GRIN2B), antidepressant action (DEPTOR, CHRNA7, NRXN1), and mood stabilizer or antipsychotic action (NTRK2, CHRNA7, NRXN1) may affect long-term treatment outcome of BD. Promising findings without previous strong evidence were TRAF3IP2-AS1, NFYC, RNLS, KCNJ2, RASGRF1, NTF3 genes. Pathway analysis supported particularly the involvement of molecules mediating the positive regulation of MAPK cascade and learning/memory processes. Further studies focused on the outlined genes may be helpful to provide validated markers of BD treatment outcome.

  5. Reach Out to Enhance Wellness in Older Cancer Survivors (RENEW): Design, Methods and Recruitment Challenges of a Home-based Exercise and Diet Intervention to Improve Physical Function among Long-term Survivors of Breast, Prostate, and Colorectal Cancer

    PubMed Central

    Snyder, Denise Clutter; Morey, Miriam C.; Sloane, Richard; Stull, Valeda; Cohen, Harvey Jay; Peterson, Bercedis; Pieper, Carl; Hartman, Terryl J.; Miller, Paige E.; Mitchell, Diane C.; Demark-Wahnefried, Wendy

    2009-01-01

    Objective Cure rates for cancer are increasing, especially for breast, prostate, and colorectal cancer. Despite positive trends in survivorship, a cancer diagnosis can trigger accelerated functional decline that can threaten independence, reduce quality-of-life and increase health care costs, especially among the elderly who comprise the majority of survivors. Lifestyle interventions may hold promise in reorienting functional decline in older cancer survivors, but few studies have been conducted. Method We describe the design and methods of a randomized controlled trial, RENEW (Reach out to ENhancE Wellness), that tests whether a home-based multi-behavior intervention focused on exercise, and including a low-saturated fat, plant-based diet, would improve physical functioning among 641 older, long-term (≥5 years post-diagnosis) survivors of breast, prostate, or colorectal cancer. Challenges to recruitment are examined. Results 20,015 cases were approached, and screened using a two-step screening process to assure eligibility. This population of long-term, elderly cancer survivors had lower rates of response (∼11%) and higher rates of ineligibility (∼70%) than our previous intervention studies conducted on adults with newly diagnosed cancer. Significantly higher response rates were noted among survivors who were white, younger, and more proximal to diagnosis and breast cancer survivors (p-values < 0.001). Conclusions Older cancer survivors represent a vulnerable population for whom lifestyle interventions may hold promise. RENEW may provide guidance in allocating limited resources in order to maximize recruitment efforts aimed at this needy, but hard-to-reach population. PMID:19117329

  6. Long-term insulin-like growth factor-I expression in skeletal muscles attenuates the enhanced in vitro proliferation ability of the resident satellite cells in transgenic mice

    NASA Technical Reports Server (NTRS)

    Chakravarthy, M. V.; Fiorotto, M. L.; Schwartz, R. J.; Booth, F. W.

    2001-01-01

    Insulin-like growth factor-I (IGF-I) overexpression for 1-month in mouse skeletal muscle increases satellite cell proliferation potential. However, it is unknown whether this beneficial enhancement by IGF-I expression would persist over a longer-term duration in aged mice. This is an important issue to address if a prolonged course of IGF-I is to be used clinically in muscle-wasting conditions where satellite cells may become limiting. Using the IGF-I transgenic (IGF-I Tg) mouse that selectively expresses the IGF-I transgene in striated muscles, we found that 18-months of continuous IGF-I overexpression led to a loss in the enhanced in vitro proliferative capacity of satellite cells from Tg skeletal muscles. Also 18-month-old IGF-I Tg satellite cells lost the enhanced BrdU incorporation, greater pRb and Akt phosphorylations, and decreased p27(Kip1) levels initially observed in cells from 1-month-old IGF-I Tg mice. The levels of those biochemical markers reverted to similar values seen in the 18-months WT littermates. These findings, therefore, suggest that there is no further beneficial effect on enhancing satellite cell proliferation ability with persistent long-term expression of IGF-I in skeletal muscles of these transgenic mice.

  7. Short-term but not long-term hypoglycaemia enhances plasma levels and hepatic expression of HSP72 in insulin-treated rats: an effect associated with increased IL-6 levels but not with IL-10 or TNF-α.

    PubMed

    Ludwig, Mirna Stela; Minguetti-Câmara, Vânia Cibele; Heck, Thiago Gomes; Scomazzon, Sofia Pizzato; Nunes, Patrícia Renck; Bazotte, Roberto Barbosa; Homem de Bittencourt, Paulo Ivo

    2014-12-01

    The inducible expression of the 70-kDa heat shock proteins (HSP70) is associated with homeostatically stressful situations. Stresses involving sympathetic nervous system (SNS) activation, including α1-adrenergic agonists and physical exercise, are capable of inducing HSP70 expression and release of the HSP70 inducible form, HSP72. However, whether hypoglycaemia is capable of influencing HSP70 status under a stressful situation such as insulin-induced hypoglycaemia (IIH), which also involves SNS activation, is unsettled. Hence, we decided to investigate whether the predominant signal for HSP70 expression and delivery into the blood comes from either low glucose, high insulin, or both during short-term IIH (STIIH) and long-term IIH (LTIIH). Our data indicated that low glucose level (up to 1.56 ± 0.14 mM), but not insulin, is the triggering factor responsible for a dramatic rise in HSP72 plasma concentrations (from 0.15 ± 0.01 in fed state to 0.77 ± 0.13 ng/mL during hypoglycaemic episodes). This was observed in parallel with up to 7-fold increases in interleukin-6 (IL-6) but not interleukin-10 (IL-10) or tumour necrosis factor-α (TNF-α) at STIIH. Together, the observations may suggest that HSP72 is released under hypoglycaemic conditions as a part of the homeostatic stress response, whereas at long-term, both hypoglycaemia and insulin may influence HSP72 expression in the liver, but not in kidneys. Secreted extracellular HSP72 (eHSP72) may be purely a danger signal to all the tissues of the body for the enhancement of immune and metabolic surveillance state or actively participates in glycaemic control under stressful situations.

  8. Nicotine shifts the temporal activation of hippocampal protein kinase A and extracellular signal-regulated kinase 1/2 to enhance long-term, but not short-term, hippocampus-dependent memory.

    PubMed

    Gould, Thomas J; Wilkinson, Derek S; Yildirim, Emre; Poole, Rachel L F; Leach, Prescott T; Simmons, Steven J

    2014-03-01

    Acute nicotine enhances hippocampus-dependent learning through nicotine binding to β2-containing nicotinic acetylcholine receptors (nAChRs), but it is unclear if nicotine is targeting processes involved in short-term memory (STM) leading to a strong long-term memory (LTM) or directly targeting LTM. In addition, the molecular mechanisms involved in the effects of nicotine on learning are unknown. Previous research indicates that protein kinase A (PKA), extracellular signal-regulated kinase 1/2 (ERK1/2), and protein synthesis are crucial for LTM. Therefore, the present study examined the effects of nicotine on STM and LTM and the involvement of PKA, ERK1/2, and protein synthesis in the nicotine-induced enhancement of hippocampus-dependent contextual learning in C57BL/6J mice. The protein synthesis inhibitor anisomycin impaired contextual conditioning assessed at 4 h but not 2 h post-training, delineating time points for STM (2 h) and LTM (4 h and beyond). Nicotine enhanced contextual conditioning at 4, 8, and 24 h but not 2 h post-training, indicating nicotine specifically enhances LTM but not STM. Furthermore, nicotine did not rescue deficits in contextual conditioning produced by anisomycin, suggesting that the nicotine enhancement of contextual conditioning occurs through a protein synthesis-dependent mechanism. In addition, inhibition of dorsal hippocampal PKA activity blocked the effect of acute nicotine on learning, and nicotine shifted the timing of learning-related PKA and ERK1/2 activity in the dorsal and ventral hippocampus. Thus, the present results suggest that nicotine specifically enhances LTM through altering the timing of PKA and ERK1/2 signaling in the hippocampus, and suggests that the timing of PKA and ERK1/2 activity could contribute to the strength of memories.

  9. 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.

  10. Long-term outcomes of major upper extremity replantations

    PubMed Central

    Ng, Wendy KY; Kaur, Manraj Nirmal; Thoma, Achilleas

    2014-01-01

    BACKGROUND: Long-term outcomes of major upper extremity replantations are infrequently reported. It is believed that replantation is indicated for amputations at all levels in children and for all distal amputations in adults. Replantations of arm or proximal forearm amputations in adults are controversial. OBJECTIVE: To evaluate the results of major upper extremity replantations, defined as those that are transmetacarpal, through the wrist, forearm, elbow or arm. METHODS: A review of these types of replantations performed at the authors’ institution from 2002 to 2012 was conducted. Patients’ strength, range of motion and two-point discrimination were assessed. Patients completed the Disabilities of the Arm, Shoulder and Hand (DASH), the Michigan Hand Questionnaire (MHQ), and the Hospital Anxiety and Depression scale (HADS). RESULTS: Seventeen patients underwent major upper extremity replantation surgery. The majority (16 of 17 [94%]) of the included patients were male. Of 17 patients, 13 (76.5%) required reoperations. The mean (± SD) DASH score of seven patients who consented to completing all questionnaires was 75.4±14.2 of 100 (range 59.2 to 91.1). On the MHQ, the mean score for affected hand function was 16% compared with 84% in the unaffected hand. Patients generally demonstrated at least mild levels of anxiety and depression on the HADS. DISCUSSION: The results suggest that major upper extremity injuries and replantations have a significant impact on patients’ long-term hand function, and produce long-term anxiety and depressive symptoms. PMID:25152640

  11. 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…

  12. Long Term Preservation of Digital Information.

    ERIC Educational Resources Information Center

    Lorie, Raymond A.

    The preservation of digital data for the long term presents a variety of challenges from technical to social and organizational. The technical challenge is to ensure that the information, generated today, can survive long term changes in storage media, devices, and data formats. This paper presents a novel approach to the problem. It distinguishes…

  13. Long-Term Nutrition: A Clinician's Guide to Successful Long-Term Enteral Access in Adults.

    PubMed

    Bechtold, Matthew L; Mir, Fazia A; Boumitri, Christine; Palmer, Lena B; Evans, David C; Kiraly, Laszlo N; Nguyen, Douglas L

    2016-09-22

    Long-term nutrition support requires long-term enteral access. To ensure the success of long-term enteral access, many factors need to be taken into consideration. This article represents a guide to placing and maintaining access in patients requiring long-term nutrition and addresses many of the common questions regarding long-term enteral access, such as indications, types of access, feeding after access placed, and recognition and treatment of potential complications. This guide will help the clinician establish and maintain access to maximize nutrition in patients requiring long-term nutrition.

  14. 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

  15. NR2B subunit-dependent long-term potentiation enhancement in the rat cortical auditory system in vivo following masking of patterned auditory input by white noise exposure during early postnatal life.

    PubMed

    Hogsden, Jennifer L; Dringenberg, Hans C

    2009-08-01

    The composition of N-methyl-D-aspartate (NMDA) receptor subunits influences the degree of synaptic plasticity expressed during development and into adulthood. Here, we show that theta-burst stimulation of the medial geniculate nucleus reliably induced NMDA receptor-dependent long-term potentiation (LTP) of field postsynaptic potentials recorded in the primary auditory cortex (A1) of urethane-anesthetized rats. Furthermore, substantially greater levels of LTP were elicited in juvenile animals (30-37 days old; approximately 55% maximal potentiation) than in adult animals (approximately 30% potentiation). Masking patterned sound via continuous white noise exposure during early postnatal life (from postnatal day 5 to postnatal day 50-60) resulted in enhanced, juvenile-like levels of LTP (approximately 70% maximal potentiation) relative to age-matched controls reared in unaltered acoustic environments (approximately 30%). Rats reared in white noise and then placed in unaltered acoustic environments for 40-50 days showed levels of LTP comparable to those of adult controls, indicating that white noise rearing results in a form of developmental arrest that can be overcome by subsequent patterned sound exposure. We explored the mechanisms mediating white noise-induced plasticity enhancements by local NR2B subunit antagonist application in A1. NR2B subunit antagonists (Ro 25-6981 or ifenprodil) completely reversed white noise-induced LTP enhancement at concentrations that did not affect LTP in adult or age-matched controls. We conclude that white noise exposure during early postnatal life results in the maintenance of juvenile-like, higher levels of plasticity in A1, an effect that appears to be critically dependent on NR2B subunit activation.

  16. Reach Out to Enhance Wellness Home-Based Diet-Exercise Intervention Promotes Reproducible and Sustainable Long-Term Improvements in Health Behaviors, Body Weight, and Physical Functioning in Older, Overweight/Obese Cancer Survivors

    PubMed Central

    Demark-Wahnefried, Wendy; Morey, Miriam C.; Sloane, Richard; Snyder, Denise C.; Miller, Paige E.; Hartman, Terryl J.; Cohen, Harvey J.

    2012-01-01

    Purpose Diet and exercise interventions have been tested in cancer survivors as a means to reduce late effects and comorbidity, but few have assessed adherence and health outcomes long term. Methods Between July 2005 and May 2007, the Reach Out to Enhance Wellness (RENEW) trial accrued 641 locoregionally staged, long-term (≥ 5 years from diagnosis) colorectal, breast, and prostate cancer survivors in the United States (21 states), Canada, and the United Kingdom. All participants were sedentary (< 150 minutes of physical activity [PA] a week), overweight or obese (body mass index, 25 to 40 kg/m2), and over age 65 years. The trial tested a diet-exercise intervention delivered via mailed print materials and telephone counseling. RENEW used a wait-list control, cross-over design (ie, participants received the year-long intervention immediately or after a 1-year delay), which allowed the opportunity to assess program efficacy (previously reported primary outcome), durability, and reproducibility (reported herein). Measures included diet quality (DQ), PA, BMI, and physical function (PF). Results No significant relapse was observed in the immediate-intervention arm for DQ, PA, and BMI; however, rates of functional decline increased when the intervention ceased. From year 1 to year 2, significant improvements were observed in the delayed-intervention arm; mean change scores in behaviors and BMI and PF slopes were as follows: DQ score, 5.2 (95% CI, 3.4 to 7.0); PA, 45.8 min/wk (95% CI, 26.9 to 64.6 min/wk); BMI, −0.56 (95% CI, −0.75 to −0.36); and Short Form-36 PF, −1.02 versus −5.52 (P < .001 for all measures). Overall, both arms experienced significant improvements in DQ, PA, and BMI from baseline to 2-year follow-up (P < .001). Conclusion Older cancer survivors respond favorably to lifestyle interventions and make durable changes in DQ and PA that contribute to sustained weight loss. These changes positively reorient functional decline trajectories during

  17. Review of long-term results of stereotactic psychosurgery.

    PubMed

    Kim, Moon-Chan; Lee, Tae-Kyu; Choi, Chang-Rak

    2002-09-01

    Stereotactic psychosurgery is an effective method for treating some medically intractable psychiatric illnesses. However, it is unfamiliar and the long-term clinical results have not been reported in Asia. The long-term results of psychosurgery are evaluated and the neuroanatomical basis is discussed. Twenty-one patients underwent stereotactic psychosurgery for medically intractable psychiatric illnesses since 1993. All were referred from psychiatrists for these disorders. Two patients showed aggressive behavior, 12 had obsessive-compulsive disorder (OCD), and seven had depression with anxiety disorders. Bilateral amygdalotomy and subcaudate tractotomy were performed for aggressive behavior, limbic leucotomy was performed for OCD, and subcaudate tractotomy with or without cingulotomy was performed for depression with anxiety. OCD was evaluated with the Yale-Brown Obsessive Compulsive Scale (YBOCS), the visual analogue scale, the Clinical Global Impression Scale, and the Overt Aggression Scale (OAS). The Mini-Mental State Examination and the Wechsler Adult Intelligence Scale-Revised were used for the evaluation of aggressive behavior. The 17-item Hamilton Depression Rating Scale (HAMD) was used for evaluation of depression. Ventriculography was used in the first seven patients and magnetic resonance imaging-guided stereotaxy was used in the recent 14 cases for localization of the target. The lesions were made with a radiofrequency lesion generator. OAS scores in the two patients with aggressive behavior during follow up declined from 8 to 2 with clinical improvement. All 12 patients with OCD returned to their previous life and showed the mean YBOCS scores decreased from 34 to 3. Ten patients with OCD could be followed up (mean 45 months). All patients returned to their previous social life. In seven patients with depression with anxiety, HAMD scores declined from 28.5 to 16.5. There was no operative mortality and no significant morbidity except for one case of mild

  18. Behavioral and systemic consequences of long-term inflammatory challenge.

    PubMed

    Fischer, Christina W; Elfving, Betina; Lund, Sten; Wegener, Gregers

    2015-11-15

    Inflammatory reactions are involved in a diversity of diseases, including major depressive disorder. Cytokines act as intercellular signaling molecules and mediators of inflammation between the periphery and the brain. Within the brain, evidence from animal studies of acute inflammation has shown that elevated cytokine levels are linked to behavioral responses of sickness and depression-like behavior. Although chronic inflammation is more translational to human depression than acute studies, little is known on central cytokine expression and associated behavioral responses following chronic immune challenges. The present study assessed behavioral changes and a selection of cytokines in the brain and in the blood in rats randomized to receive a single or 8week administration with either lipopolysaccharide (LPS, 600μg/kg, i.p.) or saline. Acute and long-term LPS treatments caused similar sickness and depression-like behavior. Chronic LPS administration did not have an effect on blood cytokine levels, indicating endotoxin tolerance, whereas increased fasting blood glucose was observed, indicating insulin resistance, a metabolic consequence of chronic inflammation. While a single LPS injection produced a generalized cytokine response in the brain, long-term LPS administration produced a specific central cytokine response with increased interleukin (IL)-1β and interferon (IFN)-γ. These cytokines can explain the behavioral changes observed, and could indicate microglia activation, although future studies are needed to uncover this assumption. Taken together, although the behavioral outcome was similar between acute and chronic LPS administration, the central cytokine response was distinct. As the long-term LPS paradigm also posed a metabolic demand, this setting may reflect a more translational insight into inflammatory reactions in human depression, and could prove useful for assessing cytokine down-stream effects and experimental antidepressant drug products.

  19. Long-term in vivo pineal microdialysis.

    PubMed

    Sun, Xing; Liu, Tiecheng; Deng, Jie; Borjigin, Jimo

    2003-09-01

    This study describes the development of a new technique for long-term measurement of daily 5-hydroxytryptamine (5-HT) and melatonin contents in the pineal gland of freely moving rats. The technique features a number of novel improvements over previous protocols. It allows visualization of the pineal gland for accurate targeting of the guide cannula, which minimizes bleeding; incurs no direct injury to the surrounding brain tissues; and causes no interference with the sympathetic innervation from the superior cervical ganglia. Robust releases of melatonin and indole precursors were continuously monitored quantitatively and reproducibly for more than 2 wk in the same animal. In addition, effects of pharmacological agents on in vivo pineal circadian rhythms can be studied reproducibly over time, and gene expression profiles can be correlated with physiological consequences in single animals. Using these approaches, it is found that beta-adrenergic activation leads to decreased release of 5-HT, and that increased cAMP signaling in vivo results in activation of N-acetyltransferase gene induction and melatonin production. These studies will enhance the understanding of signaling pathways that regulate pineal 5-HT and melatonin synthesis and secretion.

  20. 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…

  1. Roadmap to Long-Term Monitoring Optimization

    EPA Pesticide Factsheets

    This roadmap focuses on optimization of established long-term monitoring programs for groundwater. Tools and techniques discussed concentrate on methods for optimizing the monitoring frequency and spatial (three-dimensional) distribution of wells ...

  2. Mental Health in Long Term Care Settings.

    ERIC Educational Resources Information Center

    Shore, Herbert

    1978-01-01

    There are many ways in which long-term care facilities attempt to cope with the mental health problems of the elderly. The author reviews five factors crucial to effective care for the aged in these facilities. (Author/RK)

  3. Long-term-care legal update.

    PubMed

    Fiesta, J

    1998-04-01

    As more nurses move from the acute care setting to long-term-care and home health care, different practice issues arise. To maximize liability protection, nurses must understand the legal issues unique to each delivery system.

  4. Long-Term Care Ombudsman Program

    MedlinePlus

    ... Provided to Persons Living in Long-Term Care Facilities Program data for FY 2013 indicate that long- ... least quarterly Conducted 5,417 training sessions in facilities on such topics as residents’ rights Provided 129, ...

  5. The 2014 Long-Term Budget Outlook

    DTIC Science & Technology

    2014-07-16

    Treasury from the Federal Reserve System, customs duties, estate and gift taxes, and miscellaneous fees and fines. Actual Extended Baseline...Office’s (CBO’s) most recent analysis of the outlook for the federal budget over the long term. My statement today summarizes The 2014 Long-Term Budget...Outlook, which was released yesterday.1 Between 2009 and 2012, the federal government recorded the largest budget deficits relative to the size of

  6. Evidence-based long term care design.

    PubMed

    Calkins, Margaret P

    2009-01-01

    Research on the impact of the built environment in long-term care settings continues to grow. This article focuses on work conducted and published since 2000, when an earlier review on research on dementia and design was published. The vast majority of research that addressed neurological conditions in residents in long-term care settings (assisted living and nursing homes) relates to Alzheimer's disease and related dementias.

  7. 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

  8. No Evidence for Long-Term Causal Associations Between Symptoms of Premature Ejaculation and Symptoms of Anxiety, Depression, and Sexual Distress in a Large, Population-Based Longitudinal Sample.

    PubMed

    Ventus, Daniel; Gunst, Annika; Kärnä, Antti; Jern, Patrick

    2017-02-01

    Premature ejaculation (PE) is one of the most common male sexual complaints, but its etiology is unclear. Psychological problems, such as symptoms of anxiety and depression, have traditionally been seen as causal or maintaining etiological components of PE, and previous cross-sectional studies have found weak positive associations between them. The aim of the present study was to test possible causal pathways over time between PE and symptoms of the psychological problems anxiety, depression, and sexual distress. A sample of 985 male Finnish twins and brothers of twins completed a questionnaire in 2006 and 2012. Significant bivariate correlations were found both within and across time between PE and the psychological problems. When fitting structural equation models to test hypothesized causal pathways, symptoms of anxiety and sexual distress at the first measurement time point did not predict future PE. Likewise, PE symptoms at the first measurement did not predict increments or decrements in anxiety, sexual distress, or depression later on. These null findings regarding hypothesized associations may partly be explained by the relatively long time between measurements, or that the measures possibly did not capture the aspects of anxiety that are related to PE.

  9. Natural patterns of activity and long-term synaptic plasticity

    PubMed Central

    Paulsen, Ole; Sejnowski, Terrence J

    2010-01-01

    Long-term potentiation (LTP) of synaptic transmission is traditionally elicited by massively synchronous, high-frequency inputs, which rarely occur naturally. Recent in vitro experiments have revealed that both LTP and long-term depression (LTD) can arise by appropriately pairing weak synaptic inputs with action potentials in the postsynaptic cell. This discovery has generated new insights into the conditions under which synaptic modification may occur in pyramidal neurons in vivo. First, it has been shown that the temporal order of the synaptic input and the postsynaptic spike within a narrow temporal window determines whether LTP or LTD is elicited, according to a temporally asymmetric Hebbian learning rule. Second, backpropagating action potentials are able to serve as a global signal for synaptic plasticity in a neuron compared with local associative interactions between synaptic inputs on dendrites. Third, a specific temporal pattern of activity — postsynaptic bursting — accompanies synaptic potentiation in adults. PMID:10753798

  10. NLRP3 INFLAMMASOME ACTIVATION CONTRIBUTES TO LONG-TERM BEHAVIORAL ALTERATIONS IN MICE INJECTED WITH LIPOPOLYSACCHARIDE

    PubMed Central

    ZHU, WEI; CAO, FENG-SHENG; FENG, JUN; CHEN, HUA-WENG; WAN, JIE-RU; LU, QING; WANG, JIAN

    2017-01-01

    Lipopolysaccharide (LPS) might affect the central nervous system by causing neuroinflammation, which subsequently leads to brain damage and dysfunction. In this study, we evaluated the role of nod-like receptor pyrin domain-containing protein 3 (NLRP3) inflammasome activation in long-term behavioral alterations of 8-week-old male C57BL/6 mice injected intraperitoneally with LPS (5 mg/kg). At different time points after injection, we assessed locomotor function with a 24-point neurologic deficit scoring system and the rotarod test; assessed recognition memory with the novel object recognition test; and assessed emotional abnormality (anhedonia and behavioral despair) with the tail suspension test, forced swim test, and sucrose preference test. We also assessed protein expression of NLRP3, apoptosis-associated speck-like protein (ASC), and caspase-1 p10 in hippocampus by Western blotting; measured levels of interleukin (IL)-1β, IL-18, tumor necrosis factor α (TNFα), and IL-10 in hippocampus; measured TNFα and IL-1β in serum by ELISA; and evaluated microglial activity in hippocampus by Iba1 immunofluorescence. We found that LPS-injected mice displayed long-term depression-like behaviors and recognition memory deficit; elevated expression of NLRP3, ASC, and caspase-1 p10; increased levels of IL-1β, IL-18, and TNFα; decreased levels of IL-10; and increased microglial activation. These effects were blocked by the NLRP3 inflammasome inhibitor Ac-Tyr-Val-Ala-Asp-chloromethylketone. The results demonstrate proof of concept that NLRP3 inflammasome activation contributes to long-term behavioral alterations in LPS-exposed mice, probably through enhanced inflammation, and that NLRP3 inflammasome inhibition might alleviate peripheral and brain inflammation and thereby ameliorate long-term behavioral alterations in LPS-exposed mice. PMID:27923741

  11. Long-term symptom relief after septoplasty.

    PubMed

    Sundh, Carolina; Sunnergren, Ola

    2015-10-01

    The results for long-term symptom relief after septoplasty are contradictory in reviewed publications but the findings suggest that results are unsatisfactory. In this study, we analyzed and compared short- and long-term symptom relief after septoplasty and factors possibly associated with symptom relief. 111 patients that underwent septoplasty between 2008 and 2010 were included in the study. Medical charts were reviewed for preoperative characteristics and assessments. Data on short-term symptom relief (6 months) were retrieved from the Swedish National Quality Registry for Septoplasty; data on long-term symptom relief (34-70 months) were collected through a questionnaire. Upon the 34-70 month follow-up, 53% of the patients reported that symptoms either remained or had worsened and 83% reported nasal obstruction. Degree of symptom relief was significantly higher among patients not reporting nasal obstruction than among patients reporting nasal obstruction at long-term follow-up. The proportion of patients that reported "my symptoms are gone" declined from 53% after 6 months to 18% after 34-70 months. None of the factors taken into consideration, age at surgery, gender, follow-up time, primary operation/reoperation, history of nasal trauma, self-reported allergy, rhinometric obstruction, or same sided rhinometric, clinical and subjective nasal obstruction were associated with symptom relief. The long-term results after septoplasty are unsatisfactory. A majority of patients report that their symptoms remain after septoplasty.

  12. Long-term outcomes of autoimmune pancreatitis

    PubMed Central

    Ikeura, Tsukasa; Miyoshi, Hideaki; Shimatani, Masaaki; Uchida, Kazushige; Takaoka, Makoto; Okazaki, Kazuichi

    2016-01-01

    Autoimmune pancreatitis (AIP) has been considered a favorable-prognosis disease; however, currently, there is limited information on natural course of AIP during long-term follow-up. Recently published studies regarding the long-term outcomes of AIP has demonstrated the developments of pancreatic stone formation, exocrine insufficiency, and endocrine insufficiency are observed in 5%-41%, 34%-82%, and 38%-57% of patients having the disease. Furthermore, the incidence rate of developing pancreatic cancer ranges from 0% to 4.8% during the long-term follow-up. The event of death from AIP-related complications other than accompanying cancer is likely to be rare. During follow-up of AIP patients, careful surveillance for not only relapse of the disease but also development of complications at regular intervals is needed. PMID:27678359

  13. Valuing a long-term care facility.

    PubMed

    Mellen, C M

    1992-10-01

    The business valuation industry generally uses at least one of three basic approaches to value a long-term care facility: the cost approach, sales comparison approach, or income approach. The approach that is chosen and the resulting weight that is applied to it depend largely on the circumstances involved. Because a long-term care facility is a business enterprise, more weight usually is given to the income approach which factors into the estimate of value both the tangible and intangible assets of the facility.

  14. Keratoprosthesis: a long-term review.

    PubMed Central

    Barnham, J. J.; Roper-Hall, M. J.

    1983-01-01

    A keratoprosthesis (KP), is an artificial cornea which is inserted into an opacified cornea in an attempt to restore useful vision or, less commonly, to make the eye comfortable in painful keratopathy. Results o a retrospective study of 35 patients, with 55 KP insertions, are reviewed with regard to visual acuity, length of time vision is maintained, retention time, and complication. Overall there were a number of long-term real successes, eith retention of the KP and maintenance of improved vision in eyes not amenable to conventional treatment. Careful long-term follow-up was needed, with further surgical procedures often being necessary. Images PMID:6860613

  15. [Fetal pain: immediate and long term consequences].

    PubMed

    Houfflin Debarge, Véronique; Dutriez, Isabelle; Pusniak, Benoit; Delarue, Eléonore; Storme, Laurent

    2010-06-01

    Several situations are potentially painful for fetuses, such as malformations and invasive procedures. Nociceptive pathways are known to be functional at 26 weeks. Even if it is not possible to evaluate the fetal experience of pain, it is essential to examine its immediate and long-term consequences. As early as the beginning of the second trimester, hemodynamic and hormonal responses are observed following fetal nociceptive stimulation, In experimental studies, long-term changes have been noted in the corticotrop axis, subsequent responses to pain, and behavior after perinatal nociceptive stimulation.

  16. Self-complementary adeno-associated virus serotype 6 mediated knockdown of ADAMTS4 induces long-term and effective enhancement of aggrecan in degenerative human nucleus pulposus cells: A new therapeutic approach for intervertebral disc disorders

    PubMed Central

    Shenegelegn Mern, Demissew; Tschugg, Anja; Hartmann, Sebastian; Thomé, Claudius

    2017-01-01

    -mediated knockdown of ADAMTS4 showed no impact on cell viability and expression levels of other inflammatory catabolic proteins. Thus, our results are promising and may help to design long-term and less immunogenic gene therapeutic approaches in IVD disorders, which usually need prolonged therapeutic period between weeks and months. PMID:28207788

  17. Long-term studies of dopamine agonists.

    PubMed

    Hubble, Jean P

    2002-02-26

    Dopamine agonists have long been used as adjunctive therapy for the treatment of Parkinson's disease (PD). In more recent years these drugs have also been proved safe and effective as initial therapy in lieu of levodopa in the treatment of PD. Long-term levodopa therapy is associated with motor complications, including fluctuating response patterns and dyskinesia. By initially introducing a dopamine agonist as symptomatic drug therapy, it may be possible to postpone the use of levodopa and delay or prevent the development of motor complications. Recently, four clinical trials have explored this hypothesis by comparing the long-term response and side effects of levodopa with dopamine agonist therapy. The drugs studied have included ropinirole, pramipexole, cabergoline, and pergolide. In each of these projects, the occurrence of motor complications, such as wearing off and dyskinesia, was significantly less in the subjects assigned to initiation of therapy with a dopamine agonist. The addition of levodopa could be postponed by many months or even several years. Therefore, these long-term studies of dopamine agonists support the initiation of a dopamine agonist instead of levodopa in an effort to postpone levodopa-related motor complications. This therapeutic approach may be particularly appropriate in PD patients with a long treatment horizon on the basis of age and general good health. The extension phase of the long-term study comparing pramipexole with levodopa is ongoing, and follow-up information may help to establish the value of this treatment strategy.

  18. Long-Term Memory and Learning

    ERIC Educational Resources Information Center

    Crossland, John

    2011-01-01

    The English National Curriculum Programmes of Study emphasise the importance of knowledge, understanding and skills, and teachers are well versed in structuring learning in those terms. Research outcomes into how long-term memory is stored and retrieved provide support for structuring learning in this way. Four further messages are added to the…

  19. Who Recommends Long-Term Care Matters

    ERIC Educational Resources Information Center

    Kane, Robert L.; Bershadsky, Boris; Bershadsky, Julie

    2006-01-01

    Purpose: Making good consumer decisions requires having good information. This study compared long-term-care recommendations among various types of health professionals. Design and Methods: We gave randomly varied scenarios to a convenience national sample of 211 professionals from varying disciplines and work locations. For each scenario, we…

  20. Long-term lysimeter data on evapotranspiration

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Long term crop evapotranspiration (ET) data measured using large weighing lysimeters have only been gathered in a few places in the world, yet are of great importance for ground truthing of many models of plant water use, mesoscale climate, remote sensing estimation of ET, climate change and climate...

  1. Long-Term Impacts of Educational Interventions

    ERIC Educational Resources Information Center

    Deming, David James

    2010-01-01

    The school accountability movement has led to a marked increase in the use of standardized test scores to measure school and teacher productivity, yet little is known about the correlation between test score gains and improvements in long-term outcomes. In the first chapter of my dissertation, I study the impact of a school choice policy in…

  2. Long-Term Stability of Tutor Performance.

    ERIC Educational Resources Information Center

    Dolmans, Diana H. J. M.; And Others

    1996-01-01

    Examined the extent to which tutor ratings remained stable in the long term by evaluating 291 ratings of 140 tutors at Maastricht University in the Netherlands between 1992 and 1995. The results indicated that, if the aggregated score and overall judgement are used to interpret the precision of individual scores, four and two occasions,…

  3. Long-Term Stability of Social Participation

    ERIC Educational Resources Information Center

    Hyyppa, Markku T.; Maki, Juhani; Alanen, Erkki; Impivaara, Olli; Aromaa, Arpo

    2008-01-01

    The long-term stability of social participation was investigated in a representative urban population of 415 men and 579 women who had taken part in the nationwide Mini-Finland Health Survey in the years 1978-1980 and were re-examined 20 years later. Stability was assessed by means of the following tracking coefficients: kappa, proportion of…

  4. Long-term opioid therapy reconsidered.

    PubMed

    Von Korff, Michael; Kolodny, Andrew; Deyo, Richard A; Chou, Roger

    2011-09-06

    In the past 20 years, primary care physicians have greatly increased prescribing of long-term opioid therapy. However, the rise in opioid prescribing has outpaced the evidence regarding this practice. Increased opioid availability has been accompanied by an epidemic of opioid abuse and overdose. The rate of opioid addiction among patients receiving long-term opioid therapy remains unclear, but research suggests that opioid misuse is not rare. Recent studies report increased risks for serious adverse events, including fractures, cardiovascular events, and bowel obstruction, although further research on medical risks is needed. New data indicate that opioid-related risks may increase with dose. From a societal perspective, higher-dose regimens account for the majority of opioids dispensed, so cautious dosing may reduce both diversion potential and patient risks for adverse effects. Limiting long-term opioid therapy to patients for whom it provides decisive benefits could also reduce risks. Given the warning signs and knowledge gaps, greater caution and selectivity are needed in prescribing long-term opioid therapy. Until stronger evidence becomes available, clinicians should err on the side of caution when considering this treatment.

  5. Professionalism in Long-Term Care Settings

    ERIC Educational Resources Information Center

    Lubinski, Rosemary

    2006-01-01

    Speech-language pathologists who serve elders in a variety of long-term care settings have a variety of professional skills and responsibilities. Fundamental to quality service is knowledge of aging and communication changes and disorders associated with this process, institutional alternatives, and the changing nature of today's elders in…

  6. Long Term Care Aide. Course Outline.

    ERIC Educational Resources Information Center

    Wilbee, Judy

    This course outline is intended to assist the instructor in the development of a curriculum for a long-term care aide program by specifying one component of the curriculum--the objectives. These objectives, or competencies expected as outcomes for student performance on completion of the program, describe the capabilities an individual must…

  7. Evaluating Long-Term Disability Insurance Plans.

    ERIC Educational Resources Information Center

    Powell, Jan

    1992-01-01

    This report analyzes the factors involved in reviewing benefits and services of employer-sponsored group long-term disability plans for higher education institutions. Opening sections describe the evolution of disability insurance and its shape today. Further sections looks at the complex nature of "value" within a plan, relationship…

  8. LONG TERM HYDROLOGICAL IMPACT ASSESSMENT (LTHIA)

    EPA Science Inventory

    LTHIA is a universal Urban Sprawl analysis tool that is available to all at no charge through the Internet. It estimates impacts on runoff, recharge and nonpoint source pollution resulting from past or proposed land use changes. It gives long-term average annual runoff for a lan...

  9. Long-term fixed income market structure

    NASA Astrophysics Data System (ADS)

    Grilli, Luca

    2004-02-01

    Long-term fixed income market securities present a strong positive correlation in daily returns. By using a metrical approach and considering “modified” time series, I show how it is possible to show a more complex structure which depends strictly on the maturity date.

  10. Long-Term Care Research and Policy

    ERIC Educational Resources Information Center

    Kemper, Peter

    2003-01-01

    This article provides a framework for understanding how long-term care (LTC) research contributes to policy, develops a typology of research contributions to policy with examples of each type, and suggests ways to ensure that contributions continue in the future. The article draws on in-depth interviews with LTC experts working at the interface…

  11. The long term characteristics of greenschist

    NASA Astrophysics Data System (ADS)

    Jang, Bo-An

    2016-04-01

    The greenschist in the Jinping II Hydropower Station in southwest China exhibits continuous creep behaviour because of the geological conditions in the region. This phenomenon illustrates the time-dependent deformation and progressive damage that occurs after excavation. In this study, the responses of greenschist to stress over time were determined in a series of laboratory tests on samples collected from the access tunnel walls at the construction site. The results showed that the greenschist presented time-dependent behaviour under long-term loading. The samples generally experienced two stages: transient creep and steady creep, but no accelerating creep. The periods of transient creep and steady creep increased with increasing stress levels. The long-term strength of the greenschist was identified based on the variation of creep strain and creep rate. The ratio of long-term strength to conventional strength was around 80% and did not vary much with confining pressures. A quantitative method for predicting the failure period of greenschist, based on analysis of the stress-strain curve, is presented and implemented. At a confining pressure of 40 MPa, greenschist was predicted to fail in 5000 days under a stress of 290 MPa and to fail in 85 days under the stress of 320 MPa, indicating that the long-term strength identified by the creep rate and creep strain is a reliable estimate.

  12. Workshop on long-term contraceptives.

    PubMed

    1996-01-01

    The National Population Council Secretariat (NPCS) of Ghana held a three-day workshop on long-term contraceptives in 1996 in collaboration with the Ministry of Health, the Association of Voluntary Surgical Contraception, and the Johns Hopkins Population Communication Services. The session was funded by USAID. The executive director of NPCS, Dr. Richard Turkson, said that the slow rate of contraceptive acceptance was an obstacle to population control despite political concern that rapid population growth exerted an adverse impact on the economy. Only 10% of married women were using long-term or permanent methods of contraception. The hope was voiced that the participants would devise practical and cost-effective education, information, and communication (IEC) strategies to boost the demand for long-term contraceptive methods among sexually active people in Ghana. It was essential that these strategies and activities were based on a realist assessment of the demographic and social situation of the country. The examination of case studies in cultures similar to Ghana would also offer valuable lessons. The factors that hinder the acceptance of long-term methods include misconceptions, myths, and false rumors rooted in a general lack of knowledge among the people. Participants were urged to come up with strategies to counter these problems, and service providers were encouraged to improve their knowledge about contraceptive methods and counseling skills. Male involvement in contraception was also advocated. Statistics show that most Ghanians practicing contraception were using short-term methods such as foaming tablets, pills, and condoms. However, it is necessary to shift to long-term methods such as injectables, implants, and sterilization in order to achieve significant reductions in fertility.

  13. Long-term biological investigations in space.

    PubMed

    Lotz, R G; Fuchs, H; Bertsche, U

    1975-01-01

    Missions in space within the next two decades will be of longer duration than those carried out up to the present time, and the effects of such long-term flights on biological organisms are unknown. Results of biological experiments that have been performed to date cannot be extrapolated to results in future flights because of the unknown influence of adaptation over a long period of time. Prior experiments with Axolotl, fishes, and vertebrates by our research team (in part with sounding rockets) showed that these specimens did not appear to be suitable for long-term missions on which minimization of expense, technique, and energy is required. Subsequent investigations have shown the suitability of the leech (Hirudo medicinalis), which consumes blood of mammals up to ten times its own weight (1 g) and can live more than 2 years without further food supply. Emphasis in the experiments with Hirudo medicinalis is placed on metabolic rhythm and motility. Resorption and diffusion in tissue, development, and growth under long-term effects of cosmic proton radiation and zero-gravity are other focal points. The constancy of cellular life in the mature animals is a point in favor of these specimens. We have also taken into account the synergistic effects of the space environment on the problems just mentioned. The life-support system constructed for the leech has been tested successfully in four sounding rocket flights and, on that basis, has been prepared for a long-term mission. Long-term investigations out of the terrestrial biosphere will provide us with information concerning the degree of adaptation of certain physiological and biochemical functions and as to what extent biological readjustment or repair processes can occur under the specific stress conditions of space flight.

  14. Principles of Long-Term Dynamics of Dendritic Spines

    PubMed Central

    Yasumatsu, Nobuaki; Matsuzaki, Masanori; Miyazaki, Takashi; Noguchi, Jun; Kasai, Haruo

    2008-01-01

    Long-term potentiation (LTP) of synapse strength requires enlargement of dendritic spines on cerebral pyramidal neurons. Long-term depression (LTD) is linked to spine shrinkage. Indeed, spines are dynamic structures: they form, change their shapes and volumes or can disappear in the space of hours. Do all such changes result from synaptic activity, or do some changes result from intrinsic processes? How do enlargement and shrinkage of spines relate to elimination and generation of spines, and how do these processes contribute to the stationary distribution of spine volumes? To answer these questions, we recorded the volumes of many individual spines daily for several days using two-photon imaging of CA1 pyramidal neurons in cultured slices of rat hippocampus between postnatal day 17 to 23. With normal synaptic transmission, spines often changed volume or were created or eliminated, thereby showing activity-dependent plasticity. However, we found that spines changed volume even after we blocked synaptic activity, reflecting a native instability of these small structures over the long term. Such “intrinsic fluctuations” showed unique dependence on spine volume. A mathematical model constructed from these data and the theory of random fluctuations explains population behaviors of spines, such as rates of elimination and generation, stationary distribution of volumes and the long-term persistence of large spines. Our study finds that generation and elimination of spines are more prevalent than previously believed, and spine volume shows significant correlation with its age and life expectancy. The population dynamics of spines also predict key psychological features of memory. PMID:19074033

  15. Physiological, Molecular and Genetic Mechanisms of Long-Term Habituation

    SciTech Connect

    Calin-Jageman, Robert J

    2009-09-12

    Work funded on this grant has explored the mechanisms of long-term habituation, a ubiquitous form of learning that plays a key role in basic cognitive functioning. Specifically, behavioral, physiological, and molecular mechanisms of habituation have been explored using a simple model system, the tail-elicited siphon-withdrawal reflex (T-SWR) in the marine mollusk Aplysia californica. Substantial progress has been made on the first and third aims, providing some fundamental insights into the mechanisms by which memories are stored. We have characterized the physiological correlates of short- and long-term habituation. We found that short-term habituation is accompanied by a robust sensory adaptation, whereas long-term habituation is accompanied by alterations in sensory and interneuron synaptic efficacy. Thus, our data indicates memories can be shifted between different sites in a neural network as they are consolidated from short to long term. At the molecular level, we have accomplished microarray analysis comparing gene expression in both habituated and control ganglia. We have identified a network of putatively regulated transcripts that seems particularly targeted towards synaptic changes (e.g. SNAP25, calmodulin) . We are now beginning additional work to confirm regulation of these transcripts and build a more detailed understanding of the cascade of molecular events leading to the permanent storage of long-term memories. On the third aim, we have fostered a nascent neuroscience program via a variety of successful initiatives. We have funded over 11 undergraduate neuroscience scholars, several of whom have been recognized at national and regional levels for their research. We have also conducted a pioneering summer research program for community college students which is helping enhance access of underrepresented groups to life science careers. Despite minimal progress on the second aim, this project has provided a) novel insight into the network mechanisms by

  16. The long-term clinical course of generalized anxiety disorder.

    PubMed

    Keller, Martin B

    2002-01-01

    Although generalized anxiety disorder (GAD) is a common disorder associated with significant levels of morbidity, little is known of its long-term course and outcomes. During the first 5 years, GAD follows a chronic course with low rates of remission and moderate rates of relapse/recurrence following remission. Retrospective studies suggest that this chronic pattern may last up to 20 years. It is hoped that, as with depression, long-term prospective studies in GAD will provide insight into the course, nature, and outcomes of the disorder over time. The studies will also identify any changes in the duration and severity of episodes of GAD over time, enabling treatments to effectively reflect the course of the disorder. Studies of other anxiety disorders and depression suggest that the course and outcome of the disorder may be influenced by certain factors such as stressful life events, anxiety sensitivity/negative affect, gender, subsyndromal symptoms, and comorbid disorders. Currently, studies are underway to determine the effects of these factors on the risk of relapse/recurrence, maintenance of full symptoms, and development of subsyndromal symptoms in GAD. GAD is currently underrecognized and undertreated, but it is hoped that this will change with the ever-increasing awareness of anxiety disorders. As treatment for GAD becomes more common, future prospective studies will identify the effect of therapy on the course and nature of the disorder, leading to increased understanding of GAD and the development of effective treatment strategies tailored for individual patients.

  17. Using music therapy to help a client with Alzheimer's disease adapt to long-term care.

    PubMed

    Kydd, P

    2001-01-01

    The purpose of this case study is to illustrate how music therapy can be used to help the elderly successfully adjust to living in a long-term care (LTC) facility. LTC residents, particularly those with Alzheimer's disease or related dementia, may exhibit behaviors such as depression, withdrawal, anxiety, emotional liability, confusion, and memory difficulties, frequently related to the disorder, but often exacerbated by difficulty in adjustment to the change in lifestyle. The subject of this case study demonstrated these symptoms. Music therapy helped him adjust to life in a LTC setting by improving his quality of life and enhancing his relationships with those around him. As chronicled in this study, music therapy may facilitate a resident's adjustment to life in a LTC facility. N.B. Names and identifying information have been changed to protect privacy.

  18. Long-term sequelae of electrical injury

    PubMed Central

    Wesner, Marni L.; Hickie, John

    2013-01-01

    Abstract Objective To summarize the current evidence-based knowledge about the long-term sequelae of injuries from electrical current. Quality of evidence MEDLINE was searched for English-language articles published in the past 20 years using the following search terms: electrical, injuries, wound, trauma, accident, sequelae, long-term, follow-up, and aftereffects. For obvious reasons, it is unethical to randomly study electrical injury in controlled clinical trials. By necessity, this topic is addressed in less-rigorous observational and retrospective work and case studies. Therefore, the strength of the literature pertaining to the long-term sequelae of electrical injury is impaired by the necessity of retrospective methods and case studies that typically describe small cohorts. Main message There are 2 possible consequences of electrical injury: the person either survives or dies. For those who survive electrical injury, the immediate consequences are usually obvious and often require extensive medical intervention. The long-term sequelae of the electrical injury might be more subtle, pervasive, and less well defined, but can include neurologic, psychological, and physical symptoms. In the field of compensation medicine, determining causation and attributing outcome to an injury that might not result in objective clinical findings becomes a considerable challenge. Conclusion The appearance of these consequences of electrical injury might be substantially delayed, with onset 1 to 5 or more years after the electrical injury. This poses a problem for patients and health care workers, making it hard to ascribe symptoms to a remote injury when they might not arise until well after the incident event. PMID:24029506

  19. Long-term course of opioid addiction.

    PubMed

    Hser, Yih-Ing; Evans, Elizabeth; Grella, Christine; Ling, Walter; Anglin, Douglas

    2015-01-01

    Opioid addiction is associated with excess mortality, morbidities, and other adverse conditions. Guided by a life-course framework, we review the literature on the long-term course of opioid addiction in terms of use trajectories, transitions, and turning points, as well as other factors that facilitate recovery from addiction. Most long-term follow-up studies are based on heroin addicts recruited from treatment settings (mostly methadone maintenance treatment), many of whom are referred by the criminal justice system. Cumulative evidence indicates that opioid addiction is a chronic disorder with frequent relapses. Longer treatment retention is associated with a greater likelihood of abstinence, whereas incarceration is negatively related to subsequent abstinence. Over the long term, the mortality rate of opioid addicts (overdose being the most common cause) is about 6 to 20 times greater than that of the general population; among those who remain alive, the prevalence of stable abstinence from opioid use is low (less than 30% after 10-30 years of observation), and many continue to use alcohol and other drugs after ceasing to use opioids. Histories of sexual or physical abuse and comorbid mental disorders are associated with the persistence of opioid use, whereas family and social support, as well as employment, facilitates recovery. Maintaining opioid abstinence for at least five years substantially increases the likelihood of future stable abstinence. Recent advances in pharmacological treatment options (buprenorphine and naltrexone) include depot formulations offering longer duration of medication; their impact on the long-term course of opioid addiction remains to be assessed.

  20. Breakthroughs in long term care design.

    PubMed

    Hiatt, L

    1991-01-01

    In summary, here is what design is trying to accomplish in long term care facilities: Functional access; Privacy as entitlement; Sensory optimization to improve vision and hearing; Reduced walking and wheeling distances that still allow people to be mobile; Effective or functional placement of space and equipment; The option of smaller scale, so neither residents nor staff feel like they are hanging out with a unit full of, perhaps 68, people all the time; Flexibility and adaptability

  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. Titanium for long-term tritium storage

    SciTech Connect

    Heung, L.K.

    1994-12-01

    Due to the reduction of nuclear weapon stockpile, there will be an excess of tritium returned from the field. The excess tritium needs to be stored for future use, which might be several years away. A safe and cost effective means for long term storage of tritium is needed. Storing tritium in a solid metal tritide is preferred to storing tritium as a gas, because a metal tritide can store tritium in a compact form and the stored tritium will not be released until heat is applied to increase its temperature to several hundred degrees centigrade. Storing tritium as a tritide is safer and more cost effective than as a gas. Several candidate metal hydride materials have been evaluated for long term tritium storage. They include uranium, La-Ni-Al alloys, zirconium and titanium. The criteria used include material cost, radioactivity, stability to air, storage capacity, storage pressure, loading and unloading conditions, and helium retention. Titanium has the best combination of properties and is recommended for long term tritium storage.

  3. Infective endocarditis: determinants of long term outcome

    PubMed Central

    Netzer, R O M; Altwegg, S C; Zollinger, E; Täuber, M; Carrel, T; Seiler, C

    2002-01-01

    Objective: To evaluate predictors of long term prognosis in infective endocarditis. Design: Retrospective cohort study. Setting: Tertiary care centre. Patients: 212 consecutive patients with infective endocarditis between 1980 and 1995 Main outcome measures: Overall and cardiac mortality; event-free survival; and the following events: recurrence, need for late valve surgery, bleeding and embolic complications, cerebral dysfunction, congestive heart failure. Results: During a mean follow up period of 89 months (range 1–244 months), 56% of patients died. In 180 hospital survivors, overall and cardiac mortality amounted to 45% and 24%, respectively. By multivariate analysis, early surgical treatment, infection by streptococci, age < 55 years, absence of congestive heart failure, and > 6 symptoms or signs of endocarditis during active infection were predictive of improved overall long term survival. Independent determinants of event-free survival were infection by streptococci and age < 55 years. Event-free survival was 17% at the end of follow up both in medically–surgically treated patients and in medically treated patients. Conclusions: Long term survival following infective endocarditis is 50% after 10 years and is predicted by early surgical treatment, age < 55 years, lack of congestive heart failure, and the initial presence of more symptoms of endocarditis. PMID:12067947

  4. Supramolecular hydrogels for long-term bioengineered stem cell therapy.

    PubMed

    Yeom, Junseok; Kim, Su Jin; Jung, Hyuntae; Namkoong, Hong; Yang, Jeonga; Hwang, Byung Woo; Oh, Kyunghoon; Kim, Kimoon; Sung, Young Chul; Hahn, Sei Kwang

    2015-01-28

    Synthetic hydrogels have been extensively investigated as artificial extracellular matrices (ECMs) for tissue engineering in vitro and in vivo. Crucial challenges for such hydrogels are sustaining long-term cytocompatible encapsulation and providing appropriate cues at the right place and time for spatio-temporal control of the cells. Here, in situ supramolecularly assembled and modularly modified hydrogels for long-term engineered mesenchymal stem cell (eMSC) therapy are reported using cucurbit[6]uril-conjugated hyaluronic acid (CB[6]-HA), diaminohexane conjugated HA (DAH-HA), and drug-conjugated CB[6] (drug-CB[6]). The eMSCs producing enhanced green fluorescence protein (EGFP) remain alive and emit the fluorescence within CB[6]/DAH-HA hydrogels in mice for more than 60 d. Furthermore, the long-term expression of mutant interleukin-12 (IL-12M) by eMSCs within the supramolecular hydrogels results in effective inhibition of tumor growth with a significantly enhanced survival rate. Taken together, these findings confirm the feasibility of supramolecular HA hydrogels as 3D artificial ECMs for cell therapies and tissue engineering applications.

  5. Effects of Patterned Sound Deprivation on Short- and Long-Term Plasticity in the Rat Thalamocortical Auditory System In Vivo

    PubMed Central

    Soutar, Chloe N.; Rosen, Laura G.; Rodier, Simon G.; Dringenberg, Hans C.

    2016-01-01

    Postnatal sensory experience plays a significant role in the maturation and synaptic stabilization of sensory cortices, such as the primary auditory cortex (A1). Here, we examined the effects of patterned sound deprivation (by rearing in continuous white noise, WN) during early postnatal life on short- and long-term plasticity of adult male rats using an in vivo preparation (urethane anesthesia). Relative to age-matched control animals reared under unaltered sound conditions, rats raised in WN (from postnatal day 5 to 50–60) showed greater levels