Science.gov

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. Depletion of perineuronal nets enhances recognition memory and long-term depression in the perirhinal cortex

    PubMed Central

    Romberg, Carola; Yang, Sujeong; Melani, Riccardo; Andrews, Melissa R.; Horner, Alexa E.; Spillantini, Maria G.; Bussey, Timothy J.; Fawcett, James W.; Pizzorusso, Tommaso; Saksida, Lisa M.

    2013-01-01

    Perineuronal nets are extracellular matrix structures surrounding cortical neuronal cell bodies and proximal dendrites, and are involved in the control of brain plasticity and the closure of critical periods. Expression of the link protein Crtl1/Hapln1 in neurons has recently been identified as the key event triggering the formation of perineuronal nets. Here we show that the genetic attenuation of perineuronal nets in adult brain Crtl1 knockout mice enhances long term object recognition memory and facilitates long-term depression in the perirhinal cortex, a neural correlate of object recognition memory. Identical prolongation of memory follows localised digestion of perineuronal nets with chondroitinase ABC, an enzyme that degrades the chondroitin sulphate proteoglycans (CSPGs) components of PNNs. The memory-enhancing effect of chondroitinase ABC treatment attenuated over time, suggesting that regeneration of PNNs gradually restored control plasticity levels. Our findings indicate that perineuronal nets regulate both memory and experience-driven synaptic plasticity in adulthood. PMID:23595763

  3. 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

  4. 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.

  5. 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…

  6. 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…

  7. 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.

  8. 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

  9. 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.

  10. 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

  11. 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.

  12. Long-term depression at olfactory nerve synapses.

    PubMed

    Mutoh, Hiroki; Yuan, Qi; Knöpfel, Thomas

    2005-04-27

    The synapses formed by the olfactory nerve (ON) convey sensory information to olfactory glomeruli, the first stage of central odor processing. Morphological and behavioral studies suggest that glomerular odor processing is plastic in neonate rodents. However, long-term synaptic plasticity, a cellular correlate of functional and structural plasticity, has not yet been demonstrated in this system. Here, we report that ON-->mitral cell (MC) synapses of 5- to 8-d-old mice express long-term depression (LTD) after brief low-frequency ON stimulation. Pharmacological techniques and imaging of presynaptic calcium signals demonstrate that ON-MC LTD is expressed presynaptically and requires the activation of metabotropic glutamate receptors but does not require fast synaptic transmission. LTD at the ON--> MC synapse is potentially relevant for the establishment, maintenance, and experience-dependent refinement of odor maps in the olfactory bulb.

  13. 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

  14. 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.

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

    PubMed Central

    Proctor, Enola K.

    2012-01-01

    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). Researchers assessed new, consenting CLTC clients for depression using standardized research criteria in a telephone interview. Agency case records were abstracted to determine the extent to which client depression was noted. Sensitivity and specificity of depression notation were 25.21 percent and 92.80 percent, respectively, indicating that agency records reflected depression for about one in four clients meeting depression criteria. Factors associated with accurate depression notation included cognitive impairments, low social support, psychotropic medications, and mental health treatment. The depression notation rates found are comparable to those in medical settings. Structured screening and assessment might enhance detection of mental disorder for social service clients. PMID:19275120

  16. 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.

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

    PubMed Central

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

    2009-01-01

    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 assessed with the Geriatric Depression Scale prior to and following bereavement. Random effects regression growth curve analyses examined the effects of treatment group and bereavement while controlling for other variables Results The death of the care recipient led to reductions in depressive symptoms for both caregiving groups. Enhanced support intervention led to lower depressive symptoms compared with controls both before and after bereavement. Post-bereavement group differences were stronger for caregivers of spouses who did not previously experience a nursing home placement. These caregivers maintained these differences for more than 1 year after bereavement. Caregivers who received the enhanced support intervention were more likely to show long-term patterns of fewer depressive symptoms before and after bereavement, suggesting resilience, whereas control caregivers were more likely to show chronic depressive symptoms before and after the death of their spouse. Implications Caregiver intervention has the potential to alter the long-term course of the caregiving career. Such clinical strategies may also protect caregivers against chronic depressive symptoms that would otherwise persist long after caregiving ends. PMID:19139247

  18. Surviving Depression: Clinical Qualitative Analysis of Long-Term Survival for Ethnically Diverse, Depressed Patients.

    PubMed

    Miranda, Jeanne; Bromley, Elizabeth; Izquierdo, Adriana; Jones, Felica; Wells, Kenneth

    2017-08-01

    Depression is persistent and recurrent across ethnic groups. Few narrative analyses of long-term outcomes for ethnically diverse adults with depression exist. We combined 9 years of quantitative data, qualitative interviews at 10 years, clinician ratings of outcomes, and a community discussion group with the objective of describing long-term recovery and survival of diverse primary care patients after an episode of depression. Nearly half of participants were found to be depressed at some time over a 10-year period, and most cases across ethnic groups were judged to need further treatment. The ethnically diverse community members that analyzed the transcripts emphasized assets that participants showed in surviving multiple life stresses. Different sex and ethnic/racial groups had different characteristics of engaging in care, with Latino women in particular raising concerns about care engagement, coping with stress, and long-term outcomes.

  19. Systems biology perspectives on cerebellar long-term depression.

    PubMed

    Ogasawara, Hideaki; Doi, Tomokazu; Kawato, Mitsuo

    2008-01-01

    Long-term depression (LTD) at parallel fiber-Purkinje cell (PF-PC) synapses is thought to be the cellular correlate of cerebellar associative learning. The molecular processes are, in brief, phosphorylation of AMPA-type glutamate receptors (AMPARs) and their subsequent removal from the surface of the PF-PC synapse. In order to elucidate the fundamental mechanisms for cerebellar LTD and further the understanding of its computational role, we have investigated its systems biology and proposed the following hypotheses, some of which have already been experimentally verified: (1) due to the mitogen-activated protein kinase (MAPK)-protein kinase C (PKC) positive feedback loop, phosphorylation of AMPARs is an all-or-none event; (2) the inositol 1,4,5-triphosphate receptor detects concurrent PF and climbing fiber inputs, forming the cellular basis for associative learning, and (3) the local concentration of nitric oxide in the PC dendrite reflects the relevance of a given context, enabling context-dependent selection of learning modules within the cerebellum. In this review, we first introduce theoretical studies on cerebellar LTD, mainly focusing on our own published work, followed by a discussion of the effects of stochasticity, localization, diffusion, and scaffolding. Neurons embody two features that are apparently contradictory, yet necessary for synaptic memory: stability and plasticity. We will also present models for explaining how neurons solve this dilemma. In the final section, we propose a conceptual model in which a cascade of excitable dynamics with different time scales, i.e., Ca(2+)-induced Ca(2+) release, the MAPK-PKC positive feedback loop, and protein kinase Mzeta (PKMzeta)-induced PKMzeta synthesis, provides a mechanism for stable memory that is still amenable to modifications. Copyright 2008 S. Karger AG, Basel.

  20. 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…

  1. 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…

  2. Long-term incidence of depression and predictors of depressive symptoms in older stroke survivors.

    PubMed

    Allan, Louise M; Rowan, Elise N; Thomas, Alan J; Polvikoski, Tuomo M; O'Brien, John T; Kalaria, Raj N

    2013-12-01

    Depression is common and an important consequence of stroke but there is limited information on the longer-term relationship between these conditions. To identify the prevalence, incidence and predictors of depression in a secondary-care-based cohort of stroke survivors aged over 75 years, from 3 months to up to 10 years post-stroke. Depression was assessed annually by three methods: major depression by DSM-IV criteria, the self-rated Geriatric Depression Scale (GDS) and the observer-rated Cornell scale. We found the highest rates, 31.7% baseline prevalence, of depressive symptoms with the GDS compared with 9.7% using the Cornell scale and 1.2% using DSM-IV criteria. Incidence rates were 36.9, 5.90 and 4.18 episodes per 100 person years respectively. Baseline GDS score was the most consistent predictor of depressive symptoms at all time points in both univariate and multivariate analyses. Other predictors included cognitive impairment, impaired activities of daily living and in the early period, vascular risk factor burden and dementia. Our results emphasise the importance of psychiatric follow-up for those with early-onset post-stroke depression and long-term monitoring of mood in people who have had a stroke and remain at high risk of depression.

  3. Case managers speak out: responding to depression in community long-term care.

    PubMed

    Munson, Michelle; Proctor, Enola; Morrow-Howell, Nancy; Fedoravicius, Nicole; Ware, Norma

    2007-08-01

    This study sought to understand how case managers in one publicly funded health and social service system, community long-term care, understand and address depression among their clients. Four focus groups with a total of 18 case managers were conducted. Case managers were asked a series of questions about their perspectives on the recognition and treatment of depression, including subthreshold depression, in community long-term care. Case managers perceived addressing depression as complex because of competing demands. Furthermore, case managers perceived conflict between their current role and what it would take to expand their role to include addressing depression. Case managers suggested that in order to successfully improve the detection and treatment of depression in community long-term care, systemic changes, such as increased support and training, may be necessary, along with a shift in the professional role of case managers.

  4. EMDR as a treatment for long-term depression: A feasibility study.

    PubMed

    Wood, Emily; Ricketts, Thomas; Parry, Glenys

    2017-08-18

    Current treatments for long-term depression - medication and psychotherapy - are effective for some but not all clients. New approaches need to be developed to complement the ones already available. This study was designed to test the feasibility of using an effective post-traumatic stress disorder treatment for people with long-term depression. A single-case experimental design with replications was undertaken as a feasibility study of eye movement desensitization and reprocessing (EMDR) in treating long-term depression. Thirteen people with recurrent and/or long-term depression were recruited from primary care mental health services and given standard protocol EMDR for a maximum of 20 sessions. Levels of depression were measured before and after treatment and at follow-up, clients also rated their mood each day. Eight people engaged with the treatment; seven of these had clinically significant and statistically reliable improvement on the Hamilton Rating Scale for Depression. Daily mood ratings were highly variable both during baseline and intervention. EMDR is a feasible treatment for recurrent and/or long-term depression. Research on treatment efficacy and effectiveness is now required. EMDR may be an effective treatment for depression. EMDR could be considered if first-line approaches (CBT and counselling) have been tried and failed. EMDR may be particularly helpful for service users with a history of trauma. © 2017 The Authors. Psychology and Psychotherapy: Theory, Research and Practice published by John Wiley & Sons Ltd on behalf of British Psychological Society.

  5. Dependence receptor involvement in subtilisin-induced long-term depression and in long-term potentiation.

    PubMed

    Stone, Trevor W; Darlington, L Gail; Forrest, Caroline M

    2016-11-12

    The serine protease subtilisin induces a form of long-term depression (LTD) which is accompanied by a reduced expression of the axo-dendritic guidance molecule Unco-ordinated-5C (Unc-5C). One objective of the present work was to determine whether a loss of Unc-5C function contributed to subtilisin-induced LTD by using Unc-5C antibodies in combination with the pore-forming agents Triton X-100 (0.005%) or streptolysin O in rat hippocampal slices. In addition we have assessed the effect of subtilisin on the related dependence receptor Deleted in Colorectal Cancer (DCC) and used antibodies to this protein for functional studies. Field excitatory postsynaptic potentials (fEPSPs) were analyzed in rat hippocampal slices and protein extracts were used for Western blotting. Subtilisin produced a greater loss of DCC than of Unc-5C, but the antibodies had no effect on resting excitability or fEPSPs and did not modify subtilisin-induced LTD. However, antibodies to DCC but not Unc-5C did reduce the amplitude of theta-burst long-term potentiation (LTP). In addition, two inhibitors of endocytosis - dynasore and tat-gluR2(3Y) - were tested and, although the former compound had no effect on neurophysiological responses, tat-gluR2(3Y) did reduce the amplitude of subtilisin-induced LTD without affecting the expression of DCC or Unc-5C but with some loss of PostSynaptic Density Protein-95. The results support the view that the dependence receptor DCC may be involved in LTP and suggest that the endocytotic removal of a membrane protein or proteins may contribute to subtilisin-induced LTD, although it appears that neither Unc-5C nor DCC are involved in this process. Copyright © 2016 IBRO. Published by Elsevier Ltd. All rights reserved.

  6. Erythropoietin enhances hippocampal long-term potentiation and memory.

    PubMed

    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

    2008-09-09

    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. 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. 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.

  7. 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

  8. 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

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

    PubMed

    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

    2014-09-01

    Variation in the course of major depressive disorder (MDD) is not strongly predicted by existing subtype distinctions. A new subtyping approach is considered here. 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 years with an episode lasting most of the year) and severity (hospitalization for MDD, disability due to MDD). 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 it 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. 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. © 2014 Wiley Periodicals, Inc.

  10. 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

  11. 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

  12. Flexibility enhancement with vibration: Acute and long-term.

    PubMed

    Sands, William A; McNeal, Jeni R; Stone, Michael H; Russell, Elizabeth M; Jemni, Monem

    2006-04-01

    The most popular method of stretching is static stretching. Vibration may provide a means of enhancing range of motion beyond that of static stretching alone. This study sought to observe the effects of vibration on static stretching to determine whether vibration-aided static stretching could enhance range of motion acquisition more than static stretching alone in the forward split position. Ten highly trained male volunteer gymnasts were randomly assigned to experimental (N = 5) and control (N = 5) groups. The test was a forward split with the rear knee flexed to prevent pelvic misalignment. Height of the anterior iliac spine of the pelvis was measured at the lowest split position. Athletes stretched forward and rearward legs to the point of discomfort for 10 s followed by 5 s of rest, repeated four times on each leg and split position (4 min total). The experimental group stretched with the device turned on; the control group stretched with the device turned off. A pretest was followed by an acute phase posttest, then a second posttest measurement was performed following 4 wk of treatment. Difference scores were analyzed. The acute phase showed dramatic increases in forward split flexibility for both legs (P < 0.05), whereas the long-term test showed a statistically significant increase in range of motion on the right rear leg split only (P < 0.05). Effect sizes indicated large effects in all cases. This study showed that vibration can be a promising means of increasing range of motion beyond that obtained with static stretching in highly trained male gymnasts.

  13. 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

  14. Perinatal alcohol exposure in rat induces long-term depression of respiration after episodic hypoxia.

    PubMed

    Kervern, Myriam; Dubois, Christophe; Naassila, Mickael; Daoust, Martine; Pierrefiche, Olivier

    2009-04-01

    Little is known about the effects of alcohol exposure during pregnancy, which is responsible for fetal alcohol syndrome and the respiratory network functions, especially respiratory network plasticity (e.g., long-term facilitation) elicited after repeated short-lasting hypoxic episodes. The mechanism of induction of respiratory long-term facilitation involves 5-HT(2A/2C) receptors, which also participate in the response to hypoxia. Because fetal alcohol exposure is known to reduce serotonin centrally, and synaptic plasticity in the hippocampus, we hypothesized that alcohol exposure during gestation might impair respiratory long-term facilitation after hypoxic episodes. To analyze the effects of prenatal and postnatal alcohol exposure on respiratory long-term facilitation in 5- to 7-day-old rats. Respiratory frequency and amplitude were measured in vivo and in an in vitro rhythmic medullary slice before and after three hypoxia episodes or three applications of a 5-HT(2A/2C) receptor agonist in vitro. 5-HT(2A/2C) receptor mRNA was measured from the slice. Alcohol exposure impaired respiratory long-term facilitation and induced long-term depression of respiration in both in vivo and in vitro models. Alcohol altered 5-HT(2A/2C) mRNA expression, although 5-HT(2A/2C) agonist efficacy was not altered in increasing rhythmic activity in slices. However, a higher concentration of 5-HT(2A/2C) agonist was necessary to induce transient facilitation in slices from ethanol-exposed animals, suggesting disturbances in induction and maintenance mechanisms of respiratory long-term facilitation. Respiratory facilitation after repeated hypoxia was converted to long-term depression in rats treated with alcohol in utero. Alcohol exposure during pregnancy may therefore induce long-term maladaptive behavior of the respiratory system in neonates.

  15. 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.

  16. Long-term morbidity in bipolar-I, bipolar-II, and unipolar major depressive disorders.

    PubMed

    Forte, Alberto; Baldessarini, Ross J; Tondo, Leonardo; Vázquez, Gustavo H; Pompili, Maurizio; Girardi, Paolo

    2015-06-01

    Long-term symptomatic status in persons with major depressive and bipolar disorders treated clinically is not well established, although mood disorders are leading causes of disability worldwide. To pool data on long-term morbidity, by type and as a proportion of time-at-risk, based on published studies and previously unreported data. We carried out systematic, computerized literature searches for information on percentage of time in specific morbid states in persons treated clinically and diagnosed with recurrent major depressive or bipolar I or II disorders, and incorporated new data from one of our centers. We analyzed data from 25 samples involving 2479 unipolar depressive and 3936 bipolar disorder subjects (total N=6415) treated clinically for 9.4 years. Proportions of time ill were surprisingly and similarly high across diagnoses: unipolar depressive (46.0%), bipolar I (43.7%), and bipolar II (43.2%) disorders, and morbidity was predominantly depressive: unipolar (100%), bipolar-II (81.2%), bipolar-I (69.6%). Percent-time-ill did not differ between UP and BD subjects, but declined significantly with longer exposure times. The findings indicate that depressive components of all major affective disorders accounted for 86% of the 43-46% of time in affective morbidity that occurred despite availability of effective treatments. These results encourage redoubled efforts to improve treatments for depression and adherence to their long-term use. Copyright © 2015 Elsevier B.V. All rights reserved.

  17. Long-term effects of parental divorce timing on depression: A population-based longitudinal study.

    PubMed

    Chun, Sung-Youn; Jang, Suk-Yong; Choi, Jae-Woo; Shin, Jaeyong; Park, Eun-Cheol

    2016-09-08

    We examined the long-term effects of parental divorce timing on depression using longitudinal data from the Korean Welfare Panel Study. Depression symptoms were measured using the 11 items of Center for Epidemiologic Scale for Depression (CES-D-11), and we categorized parental divorce timing into 'early childhood', 'adolescent' and 'none'. Although participants who experienced parental divorce during adolescence exhibited a significantly higher CES-D-11 score (p = .0468), 'early childhood' participants displayed the most increased CES-D-11 score compared to the control group (p = .0007). Conversely, among participants who were unsatisfied with their marriage, those who experienced parental divorce in early childhood showed lower CES-D-11 scores, while 'adolescent period' participants exhibited significantly higher CES-D-11 scores (p = .0131). We concluded that timing of parental divorce exerts substantial yet varied effects on long-term depression symptoms and future marriage satisfaction. © The Author(s) 2016.

  18. 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…

  19. 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).…

  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. Self-reported depression and perceived financial burden among long-term rectal cancer survivors.

    PubMed

    Chongpison, Yuda; Hornbrook, Mark C; Harris, Robin B; Herrinton, Lisa J; Gerald, Joe K; Grant, Marcia; Bulkley, Joanna E; Wendel, Christopher S; Krouse, Robert S

    2016-11-01

    Types of surgery for rectal cancer (RC), including permanent ostomy (PO) or temporary ostomy followed by anastomosis (TO) or initial anastomosis (AN), can affect psychological and financial well-being during active treatment. However, these relationships have not been well studied among long-term survivors (≥5 years post-diagnosis). A mailed survey with 576 long-term RC survivors who were members of Kaiser Permanente was conducted in 2010-2011. Prevalence of current depression was ascertained using a score of ≤45.6 on the Short Form-12 version 2 mental component summary. Perceived financial burden was assessed using a Likert scale ranging from 0 (none) to 10 (severe). Regression analyses were used to measure associations after adjustment for covariates. The overall prevalence of depression was 24% among RC survivors with the highest prevalence among those with a history of PO (31%). The adjusted odds of depression among TO and AN survivors were lower than that among PO survivors, 0.42 (CI95% 0.20-0.89) and 0.59 (CI95% 0.37-0.93), respectively. Twenty-two percent perceived moderate-to-high current financial burden (≥4 points). PO survivors also reported higher mean financial burden than AN survivors (2.6 vs. 1.6, respectively; p = 0.002), but perceived burden comparably to TO survivors (2.3). Self-reported depression was associated with higher perceived financial burden (p < 0.001); surgical procedure history did not modify this relationship. Depression was reported frequently among these long-term RC survivors, particularly among PO survivors. Depression was associated with greater perception of financial burden. Screening for depression and assessing financial well-being might improve care among long-term RC survivors.Copyright © 2015 John Wiley & Sons, Ltd. Copyright © 2015 John Wiley & Sons, Ltd.

  3. 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.

  4. 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.

  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. 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

  7. 24-hour-restraint stress induces long-term depressive-like phenotypes in mice.

    PubMed

    Chu, Xixia; 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

    2016-09-09

    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.

  8. [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.

  9. 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.

  10. 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

  11. 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.

  12. Predicting long-term recovery from depression in community settings in Western Europe: evidence from ODIN.

    PubMed

    Dowrick, Christopher; Shiels, C; Page, H; Ayuso-Mateos, J L; Casey, P; Dalgard, O S; Dunn, G; Lehtinen, V; Salmon, P; Whitehead, M

    2011-02-01

    To test the impact of socio-economic and psychological adversity and healthcare on long-term recovery from depression. A community sample of 347 people with depressive disorders was followed up after 9 years. Baseline socio-economic adversity, social support, healthcare use, and psychiatric history were identified. Respondents completed self-report instruments on current depressive status (Beck depression inventory) and longstanding psychosocial adversity (sexual, physical or emotional abuse). Univariate analyses tested for association between recovery and respondent characteristics. Follow-up was achieved for 182 (52%) of the sample, of whom 75 (41%) indicated recovery from depression. Psychological adversity definitely and socio-economic adversity probably were associated with lack of recovery. Baseline healthcare had no apparent impact on outcome. Rurality and support after life events were associated with recovery. History of depression was associated with non-recovery. Psychological adversity is, and socio-economic adversity may be, associated with long-term non-recovery from depression in community settings.

  13. 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

  14. 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.

  15. Improvement of Depression and Anxiety After Discontinuation of Long- Term Efavirenz Treatment.

    PubMed

    Mothapo, Khutso M; Schellekens, Arnt; van Crevel, Reinout; Keuter, Monique; Grintjes-Huisman, K; Koopmans, Peter; van der Ven, Andre

    2015-01-01

    Neuropsychiatric symptoms in human immunodeficiency virus (HIV)-infected patients may be a late complication of efavirenz treatment. This study: 1) assessed the level of neuropsychiatric symptoms in HIV-infected patients on long-term efavirenz therapy; 2) explored the effect of a switch to non-efavirenz containing anti-retroviral treatment on neuropsychiatric symptoms. A consecutive series of 47 HIV-infected participants on long-term efavirenz treatment were included in an observational clinical trial. Participants completed three self-report questionnaires on neuropsychiatric symptoms. Patients switching to a non-efavirenz regimen were retested 2 weeks and 3 months after switching. Data were analyzed using repeated measures ANOVA to assess the effect of switching over time. A change in the percentage of patients scoring above norm scores after switching was analyzed using Chi square. Neuropsychiatric symptoms were common among HIV-infected patients on long-term efavirenz therapy, mainly depression, anxiety, stress, insufficiency in thinking and paranoia. After switching, these symptoms improved significantly to (near) normal levels. Our results show that neuropsychiatric symptoms are common among HIV-infected subjects and may be caused by long-term efavirenz use. Neuropsychiatric assessment, such as the Depression, Anxiety and Stress scale and Symptom Checklist 90, can identify those that may benefit from the discontinuation of efavirenz.

  16. The burden of depressive symptoms in the long-term treatment of patients with schizophrenia.

    PubMed

    Conley, Robert R; Ascher-Svanum, Haya; Zhu, Baojin; Faries, Douglas E; Kinon, Bruce J

    2007-02-01

    To prospectively measure the link between depressive symptoms and functional outcomes in the long-term treatment of people with schizophrenia. Data were drawn from a large, multi-site, 3-year, prospective, naturalistic, observational study, in which subjects with schizophrenia were assessed at enrollment and at 12-month intervals thereafter. Individuals who were "Depressed" (defined as a total score > or =16 on the Montgomery-Asberg Depression Rating Scale) at enrollment were compared to those "Non-depressed" on functional outcomes, using self-report measures, clinicians' ratings, and information from medical records. Statistical analyses included Generalized Estimation Equation and mixed regression analyses adjusted for individual characteristics. Longitudinal group comparisons across the 3-year study were augmented with a cross-sectional group comparison at enrollment. At enrollment, 39.4% (877/2228) of the participants were deemed Depressed. Across the 3-year study, the depressed cohort was significantly more likely than the Non-depressed to use relapse-related mental health services (emergency psychiatric services, sessions with psychiatrists); to be a safety concern (violent, arrested, victimized, suicidal); to have greater substance-related problems; and to report poorer life satisfaction, quality of life, mental functioning, family relationships, and medication adherence. Furthermore, changes in depressed status were associated with changes in functional outcomes. People with schizophrenia and concurrent depressive symptoms have poorer long-term functional outcomes compared to the Non-depressed. Their poorer quality of life, greater use of mental health services, and higher risk of involvement with law enforcement agencies underscore a need for special treatment interventions. Treatment of the non-psychotic dimensions of schizophrenia is a critical part of recovery.

  17. 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.

  18. 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

  19. The long-term effects of intimate partner violence on adolescent mothers’ depressive symptoms☆

    PubMed Central

    Lindhorst, Taryn; Oxford, Monica

    2008-01-01

    Adolescent mothers are at high risk of experiencing intimate partner violence (IPV) which may increase their likelihood of depressive symptoms in adulthood, yet little is known about the long-term effects of IPV on adolescent mothers’ trajectories of depressive symptoms. The study reported here uses prospective data spanning 14 years from a study of 229 adolescent mothers from Washington State, USA to evaluate the effects of adolescent exposure to IPV on the trajectories of depressive symptoms over time, as well as the likelihood of depressive symptoms at age 28 years. After controlling for levels of economic insecurity, the results indicate that adolescent IPV and an early vulnerability to depression were significantly related to the intercept, but not the slope of the adult depressive symptom trajectories. Both cumulative and concurrent IPV predicted the likelihood of depressive symptoms at age 28 years. Follow-up analyses indicate that adolescent IPV is associated with greater levels of adult IPV, and that women who report both adolescent and adult IPV have the highest mean levels of depressive symptoms. These findings suggest that exposure to IPV in adolescence may alter the life course of young women, increasing their risk for continuing exposure to intimate partner violence in adulthood and its concomitant negative mental health effects. Efforts aimed at prevention and early intervention in IPV among adolescent mothers are important components of the clinical care of young mothers. PMID:18201807

  20. The long-term effects of intimate partner violence on adolescent mothers' depressive symptoms.

    PubMed

    Lindhorst, Taryn; Oxford, Monica

    2008-03-01

    Adolescent mothers are at high risk of experiencing intimate partner violence (IPV) which may increase their likelihood of depressive symptoms in adulthood, yet little is known about the long-term effects of IPV on adolescent mothers' trajectories of depressive symptoms. The study reported here uses prospective data spanning 14 years from a study of 229 adolescent mothers from Washington State, USA to evaluate the effects of adolescent exposure to IPV on the trajectories of depressive symptoms over time, as well as the likelihood of depressive symptoms at age 28 years. After controlling for levels of economic insecurity, the results indicate that adolescent IPV and an early vulnerability to depression were significantly related to the intercept, but not the slope of the adult depressive symptom trajectories. Both cumulative and concurrent IPV predicted the likelihood of depressive symptoms at age 28 years. Follow-up analyses indicate that adolescent IPV is associated with greater levels of adult IPV, and that women who report both adolescent and adult IPV have the highest mean levels of depressive symptoms. These findings suggest that exposure to IPV in adolescence may alter the life course of young women, increasing their risk for continuing exposure to intimate partner violence in adulthood and its concomitant negative mental health effects. Efforts aimed at prevention and early intervention in IPV among adolescent mothers are important components of the clinical care of young mothers.

  1. 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.

  2. 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.

  3. 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

  4. 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.

  5. 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.

  6. Trends in long-term opioid therapy for noncancer pain among persons with a history of depression.

    PubMed

    Braden, Jennifer Brennan; Sullivan, Mark D; Ray, G Thomas; Saunders, Kathleen; Merrill, Joseph; Silverberg, Michael J; Rutter, Carolyn M; Weisner, Constance; Banta-Green, Caleb; Campbell, Cynthia; Von Korff, Michael

    2009-01-01

    We report trends in long-term opioid use among patients with a history of depression from two large health plans. Using claims data, age- and gender-adjusted rates for long-term (>90 days) opioid use episodes were calculated for 1997-2005, comparing those with and without a depression diagnosis in the prior 2 years. Opioid use characteristics were calculated for those with a long-term episode in 2005. Incident and prevalent long-term opioid use rates were three times higher in those with a history of depression. Prevalent long-term use per 1000 in patients with a history of depression increased from 69.8 to 125.9 at Group Health and from 84.3 to 117.5 at Kaiser Permanente of Northern California between 1997 and 2005. Those with a history of depression were more likely to receive a higher average daily dose, greater days supply, and Schedule II opioids than nondepressed persons. Persons with a history of depression are more likely to receive long-term opioid therapy for noncancer pain than those without a history of depression. Results suggest that long-term opioid therapy for noncancer pain is being prescribed to a different population in clinical practice than the clinical trial populations where opioid efficacy has been established.

  7. 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

  8. Six-month trajectories of self-reported depressive symptoms in long-term care.

    PubMed

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

    2016-01-01

    Depression is a common problem in long-term care (LTC) settings. We sought to characterize depression symptom trajectories over six months among older residents, and to identify resident characteristics at baseline that predict symptom trajectory. This study was a secondary analysis of data from a six-month prospective, observational, and multi-site study. Severity of depressive symptoms was assessed with the 15-item Geriatric Depression Scale (GDS) at baseline and with up to six monthly follow-up assessments. Participants were 130 residents with a Mini-Mental State Examination score of 15 or more at baseline and of at least two of the six monthly follow-up assessments. Individual resident GDS trajectories were grouped using hierarchical clustering. The baseline predictors of a more severe trajectory were identified using the Proportional Odds Model. Three clusters of depression symptom trajectory were found that described "lower," "intermediate," and "higher" levels of depressive symptoms over time (mean GDS scores for three clusters at baseline were 2.2, 4.9, and 9.0 respectively). The GDS scores in all groups were generally stable over time. Baseline predictors of a more severe trajectory were as follows: Initial GDS score of 7 or more, female sex, LTC residence for less than 12 months, and corrected visual impairment. The six-month course of depressive symptoms in LTC is generally stable. Most residents who experience a more severe symptom trajectory can be identified at baseline.

  9. Migraine Mutations Impair Hippocampal Learning Despite Enhanced Long-Term Potentiation

    PubMed Central

    Dilekoz, Ergin; Houben, Thijs; Eikermann-Haerter, Katharina; Balkaya, Mustafa; Lenselink, A. Mariette; Whalen, Michael J.; Spijker, Sabine; Ferrari, Michel D.; van den Maagdenberg, Arn M.J.M.

    2015-01-01

    To explain cognitive and memory difficulties observed in some familial hemiplegic migraine (FHM) patients, we examined hippocampal neurotransmission and plasticity in knock-in mice expressing the FHM type 1 (FHM1) R192Q gain-of function mutation in the CACNA1A gene that encodes the α1A subunit of neuronal CaV2.1 channels. We determined stimulus intensity–response curves for anterior commissure-evoked hippocampal CA1 field potentials in strata pyramidale and radiatum and assessed neuroplasticity by inducing long-term potentiation (LTP) and long-term depression (LTD) in anesthetized mice in vivo. We also studied learning and memory using contextual fear-conditioning, Morris water maze, and novel object recognition tests. Hippocampal field potentials were significantly enhanced in R192Q mice compared with wild-type controls. Stimulus intensity–response curves were shifted to the left and displayed larger maxima in the mutants. LTP was augmented by twofold in R192Q mice, whereas LTD was unchanged compared with wild-type mice. R192Q mice showed significant spatial memory deficits in contextual fear-conditioning and Morris water maze tests compared with wild-type controls. Novel object recognition was not impaired in R192Q mice; however, mice carrying the more severe S218L CACNA1A mutation showed marked deficits in this test, suggesting a genotype–phenotype relationship. Thus, whereas FHM1 gain-of-function mutations enhance hippocampal excitatory transmission and LTP, learning and memory are paradoxically impaired, providing a possible explanation for cognitive changes detected in FHM. Data suggest that abnormally enhanced plasticity can be as detrimental to efficient learning as reduced plasticity and highlight how genetically enhanced neuronal excitability may impact cognitive function. PMID:25716839

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

    PubMed

    Rissanen, Teemu; Viinamäki, Heimo; Honkalampi, Kirsi; Lehto, Soili M; Hintikka, Jukka; Saharinen, Tarja; Koivumaa-Honkanen, Heli

    2011-08-23

    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. 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. 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. MDD in 1999 was based on self-reports and not on structured interview and LS data in 2001-2005 was not available. The life satisfaction burden is significantly related to major depressive disorder and poor mental health, both in cross-sectional and longitudinal settings.

  11. Self-Rated Health and Long-Term Prognosis of Depression

    PubMed Central

    Ambresin, Gilles; Chondros, Patty; Dowrick, Christopher; Herrman, Helen; Gunn, Jane M.

    2014-01-01

    PURPOSE Indicators of prognosis should be considered to fully inform clinical decision making in the treatment of depression. This study examines whether self-rated health predicts long-term depression outcomes in primary care. METHODS Our analysis was based on the first 5 years of a prospective 10-year cohort study underway since January 2005 conducted in 30 randomly selected Australian primary care practices. Participants were 789 adult patients with a history of depressive symptoms. Main outcome measures include risks, risk differences, and risk ratios of major depressive syndrome (MDS) on the Patient Health Questionnaire. RESULTS Retention rates during the 5 years were 660 (84%), 586 (74%), 560 (71%), 533 (68%), and 517 (66%). At baseline, MDS was present in 27% (95% CI, 23%–30%). Cross-sectional analysis of baseline data showed participants reporting poor or fair self-rated health had greater odds of chronic illness, MDS, and lower socioeconomic status than those reporting good to excellent self-rated health. For participants rating their health as poor to fair compared with those rating it good to excellent, risk ratios of MDS were 2.10 (95% CI, 1.60–2.76), 2.38 (95% CI, 1.77–3.20), 2.22 (95% CI, 1.70–2.89), 1.73 (95% CI, 1.30–2.28), and 2.15 (95% CI, 1.59–2.90) at 1, 2, 3, 4, and 5 years, after accounting for missing data using multiple imputation. After adjusting for age, sex, multimorbidity, and depression status and severity, self-rated health remained a predictor of MDS up to 5 years. CONCLUSIONS Self-rated health offers family physicians an efficient and simple way to identify patients at risk of poor long-term depression outcomes and to inform therapeutic decision making. PMID:24445104

  12. 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

  13. 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

  14. Effect of Talbinah food consumption on depressive symptoms among elderly individuals in long term care facilities, randomized clinical trial

    PubMed Central

    Badrasawi, Manal M; Shahar, Suzana; Manaf, Zahara Abd; Haron, Hasnah

    2013-01-01

    Talbinah is a barley syrup cooked with milk and sweetened by honey. In his famous Hadith on Talbinah, the Prophet Mohammad (SAW) recommended it when sad events happen for its effect on soothing hearts and relieving sadness. This 3-week crossover designed, randomized clinical trial was conducted to determine the effect of Talbinah on mood and depression among institutionalized elderly people in Seremban. A sample of 30 depressed elderly subjects (21 men and 9 women) was selected from the long term care facility. Three different interview-based validated scales (Geriatric Depression Scale, Depression Anxiety Stress Scales, and Profile of Mood States) were used to determine mood, depression, stress, and anxiety at week 0, 3, 4, and 7. The nutritional value of Talbinah was examined using proximate food analysis, minerals content analysis, and differential amino acid analysis. The results indicated that Talbinah is a high carbohydrate food (86.4%) and has a high tryptophan: branch chain amino acids ratio (1:2). A Wilcoxon nonparametric test showed that there was a statistically significant decrease on depression, stress, and mood disturbances scores among the intervention group (P < 0.05) for all parameters. In conclusion, Talbinah has the potential to reduce depression and enhance mood among the subjects. Ingestion of functional foods such as Talbinah may provide a mental health benefit to elderly people. PMID:23493965

  15. Effect of Talbinah food consumption on depressive symptoms among elderly individuals in long term care facilities, randomized clinical trial.

    PubMed

    Badrasawi, Manal M; Shahar, Suzana; Abd Manaf, Zahara; Haron, Hasnah

    2013-01-01

    Talbinah is a barley syrup cooked with milk and sweetened by honey. In his famous Hadith on Talbinah, the Prophet Mohammad (SAW) recommended it when sad events happen for its effect on soothing hearts and relieving sadness. This 3-week crossover designed, randomized clinical trial was conducted to determine the effect of Talbinah on mood and depression among institutionalized elderly people in Seremban. A sample of 30 depressed elderly subjects (21 men and 9 women) was selected from the long term care facility. Three different interview-based validated scales (Geriatric Depression Scale, Depression Anxiety Stress Scales, and Profile of Mood States) were used to determine mood, depression, stress, and anxiety at week 0, 3, 4, and 7. The nutritional value of Talbinah was examined using proximate food analysis, minerals content analysis, and differential amino acid analysis. The results indicated that Talbinah is a high carbohydrate food (86.4%) and has a high tryptophan: branch chain amino acids ratio (1:2). A Wilcoxon nonparametric test showed that there was a statistically significant decrease on depression, stress, and mood disturbances scores among the intervention group (P < 0.05) for all parameters. In conclusion, Talbinah has the potential to reduce depression and enhance mood among the subjects. Ingestion of functional foods such as Talbinah may provide a mental health benefit to elderly people.

  16. Long term outcome of thermal anterior capsulotomy for chronic, treatment refractory depression.

    PubMed

    Christmas, David; Eljamel, M Sam; Butler, Sharon; Hazari, Hiral; MacVicar, Robert; Steele, J Douglas; Livingstone, Alison; Matthews, Keith

    2011-06-01

    There is very limited evidence for the efficacy of any specific therapeutic intervention in chronic, treatment refractory major depression. Thermal anterior capsulotomy (ACAPS) is a rarely performed but established therapeutic procedure for this patient group. While benefit has been claimed, previous ACAPS reports have provided limited information. Detailed prospective reporting of therapeutic effects and side effects is required. To report a prospective study of therapeutic effect, mental status, quality of life, social functioning and neurocognitive functioning in individuals with chronic treatment refractory major depression, treated with ACAPS. A prospective case series of 20 patients treated with ACAPS between 1992 and 1999 were reassessed at a mean follow-up of 7.0±3.4 years. Data were collected preoperatively and at long term follow-up. Structural MRI was performed in 14 participants. According to a priori criteria, at long term follow-up, 50% were classified as 'responders' and 40% as 'remitters'. Fifty-five per cent were classified as 'improved'; 35% were 'unchanged'; and 10% had 'deteriorated'. Neurocognitive and personality testing were not significantly different at follow-up. A trend towards improvement in some aspects of executive neuropsychological functioning was observed. Significant adverse effects were infrequent and there were no deaths. ACAPS may represent an effective intervention for some patients with chronic, disabling, treatment refractory major depression that has failed to respond to other therapeutic approaches. The adverse effect burden within this population was modest, with no evidence of generalised impairment of neurocognitive functioning.

  17. Childhood attachment and abuse: long-term effects on adult attachment, depression, and conflict resolution.

    PubMed

    Styron, T; Janoff-Bulman, R

    1997-10-01

    The primary aim was to determine the relative contributions of early attachment and abuse history to adult attachment, depression, and conflict resolution behaviors. Differences between abused and nonabused respondents were also assessed. A multi-scale questionnaire was completed by 879 college students. Hierarchical regression analyses were used to answer the primary research question, and analyses also compared the 26.4% of respondents who reported childhood abuse with those who did not. Respondents who indicated they had been abused as children reported less secure childhood and adult relationships than their nonabused counterparts. They were also more depressed and more likely to use destructive behaviors in conflict situations. Although both adult romantic attachment and respondents' depression scores were best accounted for by childhood attachment to mother and father rather than abuse history, the opposite pattern of results emerged for conflict resolution behaviors. In this case, abuse history was the stronger predictor, and parental attachment did not account for any significant additional variance. Results suggest that the long-term impact of childhood abuse may be mediated by early attachment experiences, whereas the long-term impact of abuse on conflict resolution behaviors may be considerably more direct.

  18. Cognitive tolerability following successful long term treatment of major depression and anxiety disorders with SSRi antidepressants.

    PubMed

    Popovic, Dina; Vieta, Eduard; Fornaro, Michele; Perugi, Giulio

    2015-03-01

    The present study aims to evaluate cognitive tolerability profile of SSRIs in long-term treatment. The secondary aim is to explore differences of side effects profile between patients with major depression (MD) and anxiety disorders (AD). Sixty-seven consecutive patients, successfully treated with SSRIs in monotherapy for at least six months for MD or AD, were assessed for side effects, with a special focus on cognition. Over 20% of MD and AD patients in long term treatment with SSRIs reported cognitive symptoms including fatigue, inattentiveness, lack of concentration, memory impairment and apathy. Recall memory impairment, attention deficit and somnolence were most frequently rated as moderate or severe. There were no significant differences in SSRI cognitive side effects profile between MD and AD patients. Subjective measure of cognitive functioning, limited sample size, lack of a control group. A large proportion of depressed and anxious patients treated successfully with SSRIs for over six months reported cognitive, affective, motivational symptoms. These symptoms are likely to represent SSRI side effects rather than residual depressive symptomatology. Copyright © 2014 Elsevier B.V. All rights reserved.

  19. Relapse rates after psychotherapy for depression - stable long-term effects? A meta-analysis.

    PubMed

    Steinert, Christiane; Hofmann, Mareike; Kruse, Johannes; Leichsenring, Falk

    2014-10-01

    Depression is the most common mental disorder. Effective psychotherapeutic treatments for depression exist; however, data on their long-term effectiveness beyond a time span of two years is still scarce. Our aim was to perform a meta-analysis, investigating (a) overall rates of relapse more than two years after psychotherapy (meta-analysis 1), and (b) if psychotherapy has more enduring effects than non-psychotherapeutic comparison conditions (e.g. pharmacotherapy, treatment as usual), again beyond a time span of two years post-therapy (meta-analysis 2). We searched electronic databases Medline, PsycINFO and the COCHRANE Library. Main selection criteria were (i) RCT of psychotherapy with follow-up interval of more than 2 years, (ii) primary diagnosis of depression, assessed by observer ratings, (iii) report of relapse at follow-up. We identified 11 studies, 6 of which included a non-psychotherapeutic comparison condition. Together they comprised long-term data of 966 patients. Mean follow-up duration was 4.4 years. The overall relapse rate at long-term follow-up was 0.39 (95% CI 0.29, 0.50). Psychotherapy resulted in significantly less relapses (53.1% vs. 71.1%, OR 0.51; 95% CI 0.32, 0.82, p=0.005) than comparison treatments. This finding corresponded to a number needed to treat (NNT) of 5.55. Results can only be preliminary as data was sparse and studies differed methodologically. Heterogeneity in the first meta-analysis was high (I(2)=82%). Results indicated publication bias. The relapse rate more than two years after psychotherapy is relatively high, but significantly lower compared to non-psychotherapeutic treatments. Multiannual follow-ups should routinely be included in future psychotherapy RCTs. Copyright © 2014 Elsevier B.V. All rights reserved.

  20. Comparison of major depressive disorder and subthreshold depression among older adults in community long-term care.

    PubMed

    Lee, Mi Jin; Hasche, Leslie K; Choi, Sunha; Proctor, Enola K; Morrow-Howell, Nancy

    2013-01-01

    This study extends existing knowledge regarding the continuum between major depression (MD) and subthreshold depression (SD) by examining differences in symptomology and associative factors for a subpopulation of older adults with functional disability. Our sample consisted of clients age 60 and above entering public community long term care derived from the baseline survey of a longitudinal study (315 non-depressed, 74 MD, and 221 SD). We used the Diagnostic Interview Schedule to establish diagnoses of MD, the Center for Epidemiological Studies Depression Scale (CES-D) to assess SD, and other self-report measures to explore potential associative factors of demographics, comorbidity, social support, and stressors. No differences in CES-D identified symptoms occurred between the two groups. MD and SD were both associated with lower education, poorer social support, more severe medical conditions, and higher stress when compared to non-depressed older adults. Younger age and being female were associated solely with MD; whereas, worse perceived health and more trouble affording food were associated solely with SD. The only associative factor significantly different between MD and SD was age. Those with MD were more likely to be younger than those with SD. Our findings of symptom profiles and associative factors lend support to the continuum notion of depression. Identification of only older adults within the community long-term care service system who meet criteria for MD would leave many older adults, who also face multiple comorbidities, high levels of stress and social isolation, and substantial depressive symptoms undiagnosed and untreated.

  1. 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

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

    PubMed Central

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

    2014-01-01

    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. PMID:24561996

  4. SPIN90 Modulates Long-Term Depression and Behavioral Flexibility in the Hippocampus.

    PubMed

    Kim, Dae Hwan; Kang, Minkyung; Kim, Chong-Hyun; Huh, Yun Hyun; Cho, In Ha; Ryu, Hyun-Hee; Chung, Kyung Hwun; Park, Chul-Seung; Rhee, Sangmyung; Lee, Yong-Seok; Song, Woo Keun

    2017-01-01

    The importance of actin-binding proteins (ABPs) in the regulation of synapse morphology and plasticity has been well established. SH3 protein interacting with Nck, 90 kDa (SPIN90), an Nck-interacting protein highly expressed in synapses, is essential for actin remodeling and dendritic spine morphology. Synaptic targeting of SPIN90 to spine heads or dendritic shafts depends on its phosphorylation state, leading to blockage of cofilin-mediated actin depolymerization and spine shrinkage. However, the physiological role of SPIN90 in long-term plasticity, learning and memory are largely unknown. In this study, we demonstrate that Spin90-knockout (KO) mice exhibit substantial deficits in synaptic plasticity and behavioral flexibility. We found that loss of SPIN90 disrupted dendritic spine density in CA1 neurons of the hippocampus and significantly impaired long-term depression (LTD), leaving basal synaptic transmission and long-term potentiation (LTP) intact. These impairments were due in part to deficits in AMPA receptor endocytosis and its pre-requisites, GluA1 dephosphorylation and postsynaptic density (PSD) 95 phosphorylation, but also by an intrinsic activation of Akt-GSK3β signaling as a result of Spin90-KO. In accordance with these defects, mice lacking SPIN90 were found to carry significant deficits in object-recognition and behavioral flexibility, while learning ability was largely unaffected. Collectively, these findings demonstrate a novel modulatory role for SPIN90 in hippocampal LTD and behavioral flexibility.

  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. Cerebral blood flow velocity positively correlates with brain volumes in long-term remitted depression.

    PubMed

    Desmidt, Thomas; Andersson, Frédéric; Brizard, Bruno; Cottier, Jean-Philippe; Patat, Frédéric; Gissot, Valérie; Belzung, Catherine; El-Hage, Wissam; Camus, Vincent

    2017-09-20

    Mechanisms involved in brain changes observed in major depression have been poorly investigated in clinical populations. Changes in cerebral blood flow (CBF) have been found in depressed patients and constitute a potential mechanism by which brain volume varies in depression. We have tested the association of cerebral blood flow velocity (CBFV) as assessed with Transcranial Doppler (TCD) and cerebral blood flow (CBF) as assessed with Arterial Spin Labeling Magnetic Resonance Imaging (ASL-MRI) with Total Brain Volume (TBV) and the volume of seven subcortical regions, in currently depressed and long-term remitted patients. In addition, we have evaluated other potential confounders for the association depression/brain volume, including dimensional symptoms of depression, cardiovascular risk factors (CVRF) and antidepressants. Seventy-five individuals were recruited, divided in 3 equal groups (currently depressed, remitted individuals and healthy controls) and were submitted to clinical assessment, MRI and Transcranial Doppler. CBFV was positively correlated with TBV, Hippocampus and Thalamus volume, but only in remitted patients, who tend to have larger brains compared to both currently depressed and controls. CVRF were negatively associated with brain volumes in the 3 groups and antidepressant use was associated with larger Thalamus. We found no association between brain volumes and CBF as assessed with ASL-MRI, anhedonia, anxiety or psychomotor retardation. Greater CBFV may be a physiological mechanism by which brain is enlarged in remitted patients. Future studies should consider CBFV, CVRF and antidepressants as possible confounders for the association depression/brain volumes, especially in remitted patients. Copyright © 2017 Elsevier Inc. All rights reserved.

  7. 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

  8. 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.

  9. Non-apoptotic function of BAD and BAX in long-term depression of synaptic transmission

    PubMed Central

    Jiao, Song; Li, Zheng

    2011-01-01

    Summary It has recently been found that caspases not only function in apoptosis, but are also crucial for non-apoptotic processes such as NMDA receptor-dependent long-term depression (LTD) of synaptic transmission. It remains unknown, however, how caspases are activated and how neurons escape death in LTD. Here we show that caspase-3 is activated by the BAD-BAX cascade for LTD induction. This cascade is required specifically for NMDA receptor-dependent LTD but not for mGluR-LTD, and its activation is sufficient to induce synaptic depression. In contrast to apoptosis, however, BAD is activated only moderately and transiently and BAX is not translocated to mitochondria, resulting in only modest caspase-3 activation. We further demonstrate that the intensity and duration of caspase-3 activation determin whether it leads to cell death or LTD, thus fine-tuning of caspase-3 activation is critical in distinguishing between these two pathways. PMID:21609830

  10. Long-term changes in sleep and depressive symptoms of smokers in abstinence.

    PubMed

    Moreno-Coutiño, Ana; Calderón-Ezquerro, Carmen; Drucker-Colín, René

    2007-03-01

    Few studies have evaluated the impact of smoking cessation on objective measures of sleep. The present study assessed the long-term effects of tobacco smoking abstinence on sleep and depression. A total of 15 chronic smokers with Hamilton Rating Scale for Depression (HAM-D) scores of less than 9 were evaluated. Subjects were screened for baseline data when they were smoking chronically. They underwent a 5-week psychological treatment for tobacco smoking, after which their depressive symptoms and sleep architecture were evaluated at 1, 2, 4, 6, 9, and 12 months of abstinence. We report the results of the seven patients who completed 1 year of evaluations and of those patients who achieved only partial abstinence. Polysomnographic recordings were taken, level of depression was measured with the HAM-D, and urinary cotinine levels also were evaluated. HAM-D scores were analyzed with and without sleep items. Nicotine abstinence reduced latency to rapid eye movement (REM) sleep and increased HAM-D scores, suggesting that chronic smokers have depressive symptoms that may be controlled by nicotine administration.

  11. Posttraumatic Stress Disorder Increases Sensitivity to Long Term Losses among Patients with Major Depressive Disorder

    PubMed Central

    Vaughan, Christopher; Paulus, Martin P.; Dunlop, Boadie W.

    2013-01-01

    decision-making about long-term potential losses compared to MDD patients without PTSD. PMID:24116235

  12. 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

  13. 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.

  14. [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.

  15. 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.

  16. 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.

  17. 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.

  18. Loss of long-term depression in the insular cortex after tail amputation in adult mice

    PubMed Central

    2014-01-01

    The insular cortex (IC) is an important forebrain structure involved in pain perception and taste memory formation. Using a 64-channel multi-electrode array system, we recently identified and characterized two major forms of synaptic plasticity in the adult mouse IC: long-term potentiation (LTP) and long-term depression (LTD). In this study, we investigate injury-related metaplastic changes in insular synaptic plasticity after distal tail amputation. We found that tail amputation in adult mice produced a selective loss of low frequency stimulation-induced LTD in the IC, without affecting (RS)-3,5-dihydroxyphenylglycine (DHPG)-evoked LTD. The impaired insular LTD could be pharmacologically rescued by priming the IC slices with a lower dose of DHPG application, a form of metaplasticity which involves activation of protein kinase C but not protein kinase A or calcium/calmodulin-dependent protein kinase II. These findings provide important insights into the synaptic mechanisms of cortical changes after peripheral amputation and suggest that restoration of insular LTD may represent a novel therapeutic strategy against the synaptic dysfunctions underlying the pathophysiology of phantom pain. PMID:24398034

  19. B-vitamins reduce the long-term risk of depression after stroke: The VITATOPS-DEP trial.

    PubMed

    Almeida, Osvaldo P; Marsh, Kylie; Alfonso, Helman; Flicker, Leon; Davis, Timothy M E; Hankey, Graeme J

    2010-10-01

    The consumption of certain B-vitamins through diet or supplementation decreases the total plasma concentration of homocysteine (tHcy) and may enhance response to standard antidepressant treatment. It is unclear if treatment with B-vitamins can reduce the long-term prevalence of depression in people at risk, such as stroke survivors. The purpose of this research was to determine if treatment with B-vitamins reduces the hazard of poststroke depression compared with placebo. Randomized, double-blind, placebo-controlled trial of tHcy-lowering treatment with daily folic acid (2 mg), vitamin B6 (25 mg), and vitamin B12 (0.5 mg) for 1 to 10.5 years in survivors of stroke. The primary endpoint was the onset of Diagnostic and Statistical Manual of Mental Disorders, 4th edition (DSM-IV) major depression after randomization. Secondary outcomes were the prevalence of DSM-IV major or minor depression at the end of treatment. Other measured factors included age, gender, poststroke handicap associated with stroke, recurrence of strokes, cognitive impairment, and use of antidepressants. Among 273 people who completed the final assessment after 7.1 ± 2.1 years (mean ± standard deviation) of follow up, random assignment to B-vitamins was associated with a lower hazard of major depression compared with placebo (18.4% vs 23.3%, adjusted hazard ratio [HR] = 0.48; 95% confidence interval [CI] = 0.31-0.76) and a trend toward a lower odds of major or minor depression at the end of the trial compared with placebo (19.1% vs 27.7%; adjusted odds ratio [OR] = 0.58; 95%CI = 0.31-1.09). Long-term treatment of poststroke survivors with folic acid, B6, and B12 was associated with a reduction in the hazard of major depression in our patient population. If these findings can be validated externally, B-vitamin supplementation offers hope as an effective, safe, and affordable intervention to reduce the burden of poststroke depression.

  20. May duration of untreated illness influence the long-term course of major depressive disorder?

    PubMed

    Altamura, A Carlo; Dell'osso, Bernardo; Vismara, Serena; Mundo, Emanuela

    2008-03-01

    The aim of this naturalistic study was to investigate the possible influence of the duration of untreated illness (DUI) on the long-term course of Major Depressive Disorder (MDD). One hundred and thirteen patients with recurrent MDD, according to DSM-IV-TR criteria, followed up for 5 years, were selected, interviewed and their clinical charts were reviewed. The DUI was defined as the interval between the onset of the first depressive episode and the first adequate antidepressant treatment. The sample was divided into two groups according to the DUI: one group with a DUI12 months (n=38). The main demographic and clinical course variables were compared between the two groups using Student's t-tests or chi-square tests. Patients with a longer DUI showed an earlier age at onset (t=2.82, p=0.006) and a longer duration of illness (t=3.20, p=0.002) compared to patients with a shorter DUI. In addition, the total number of depressive episodes occurring before the first antidepressant treatment was higher in the group with a longer DUI (t=-2.223, p<0.03). Even though limited by the retrospective nature of the study, these preliminary findings would suggest that a longer DUI may negatively influence the course of MDD. Larger prospective studies are warranted to further investigate the role of the DUI within MDD.

  1. 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

  2. [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.

  3. 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

  4. Insulin induces long-term depression of VTA dopamine neurons via an endocannabinoid-mediated mechanism

    PubMed Central

    Labouèbe, Gwenaël; Liu, Shuai; Dias, Carine; Zou, Haiyan; Wong, Jovi C.Y.; Karunakaran, Subashini; Clee, Susanne M.; Phillips, Anthony; Boutrel, Benjamin; Borgland, Stephanie L.

    2014-01-01

    The prevalence of obesity has drastically increased over the last few decades. Exploration into how hunger and satiety signals influence the reward system can help us to understand non-homeostatic mechanisms of feeding. Evidence suggests that insulin may act in the ventral tegmental area (VTA), a critical site for reward-seeking behavior, to suppress feeding. However, the neural mechanisms underlying insulin effects in the VTA remain unknown. We demonstrate that insulin, a circulating catabolic peptide that inhibits feeding, can induce a long-term depression (LTD) of excitatory synapses onto VTA dopamine neurons. This effect requires endocannabinoid-mediated presynaptic inhibition of glutamate release. Furthermore, after a sweetened high fat meal, which elevates endogenous insulin levels, insulin-induced LTD is occluded. Finally, insulin in the VTA reduces food anticipatory behavior and conditioned place preference for food. Taken together, these results suggest that insulin in the VTA suppresses excitatory synaptic transmission and reduces salience of food-related cues. PMID:23354329

  5. 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.

  6. 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

  7. 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.

  8. Postsynaptic Signals Mediating Induction of Long-Term Synaptic Depression in the Entorhinal Cortex

    PubMed Central

    Kourrich, Saïd; Glasgow, Stephen D.; Caruana, Douglas A.; Chapman, C. Andrew

    2008-01-01

    The entorhinal cortex receives a large projection from the piriform cortex, and synaptic plasticity in this pathway may affect olfactory processing. In vitro whole cell recordings have been used here to investigate postsynaptic signalling mechanisms that mediate the induction of long-term synaptic depression (LTD) in layer II entorhinal cortex cells. To induce LTD, pairs of pulses, using a 30-millisecond interval, were delivered at 1 Hz for 15 minutes. Induction of LTD was blocked by the NMDA receptor antagonist APV and by the calcium chelator BAPTA, consistent with a requirement for calcium influx via NMDA receptors. Induction of LTD was blocked when the FK506 was included in the intracellular solution to block the phosphatase calcineurin. Okadaic acid, which blocks activation of protein phosphatases 1 and 2a, also prevented LTD. Activation of protein phosphatases following calcium influx therefore contributes to induction of LTD in layer II of the entorhinal cortex. PMID:18670611

  9. 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.

  10. PICK1 interacts with PACSIN to regulate AMPA receptor internalization and cerebellar long-term depression.

    PubMed

    Anggono, Victor; Koç-Schmitz, Yeliz; Widagdo, Jocelyn; Kormann, Jan; Quan, Annie; Chen, Chih-Ming; Robinson, Phillip J; Choi, Se-Young; Linden, David J; Plomann, Markus; Huganir, Richard L

    2013-08-20

    The dynamic trafficking of AMPA receptors (AMPARs) into and out of synapses is crucial for synaptic transmission, plasticity, learning, and memory. The protein interacting with C-kinase 1 (PICK1) directly interacts with GluA2/3 subunits of the AMPARs. Although the role of PICK1 in regulating AMPAR trafficking and multiple forms of synaptic plasticity is known, the exact molecular mechanisms underlying this process remain unclear. Here, we report a unique interaction between PICK1 and all three members of the protein kinase C and casein kinase II substrate in neurons (PACSIN) family and show that they form a complex with AMPARs. Our results reveal that knockdown of the neuronal-specific protein, PACSIN1, leads to a significant reduction in AMPAR internalization following the activation of NMDA receptors in hippocampal neurons. The interaction between PICK1 and PACSIN1 is regulated by PACSIN1 phosphorylation within the variable region and is required for AMPAR endocytosis. Similarly, the binding of PICK1 to the ubiquitously expressed PACSIN2 is also regulated by the homologous phosphorylation sites within the PACSIN2-variable region. Genetic deletion of PACSIN2, which is highly expressed in Purkinje cells, eliminates cerebellar long-term depression. This deficit can be fully rescued by overexpressing wild-type PACSIN2, but not by a PACSIN2 phosphomimetic mutant, which does not bind PICK1 efficiently. Taken together, our data demonstrate that the interaction of PICK1 and PACSIN is required for the activity-dependent internalization of AMPARs and for the expression of long-term depression in the cerebellum.

  11. 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.

  12. 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…

  13. Long-Term Outcome of Adolescent Depression Initially Resistant to SSRI Treatment

    PubMed Central

    Vitiello, Benedetto; Emslie, Graham; Clarke, Gregory; Wagner, Karen D.; Asarnow, Joan R.; Keller, Martin; Birmaher, Boris; Ryan, Neal; Kennard, Betsy; Mayes, Taryn; DeBar, Lynn; Lynch, Frances; Dickerson, John; Strober, Michael; Suddath, Robert; McCracken, James T.; Spirito, Anthony; Onorato, Matthew; Zelazny, Jamie; Porta, Giovanna; Iyengar, Satish; Brent, David

    2011-01-01

    Objective We examined the long-term outcome of participants in the Treatment of SSRI-Resistant Depression in Adolescents (TORDIA) study, a randomized trial of 334 adolescents (aged 12-18 years) with DSM-IV-defined major depression disorder initially resistant to selective serotonin reuptake inhibitor (SSRI) treatment who were and subsequently treated for 12 weeks with another SSRI, venlafaxine, another SSRI + cognitive behavioral therapy (CBT), or venlafaxine + CBT. Responders then continued with the same treatment through week 24, while non-responders were given open treatment. Method For the current study, patients were reassessed 48 (N=116) and 72 (N=130) weeks from intake. Data were gathered from February 2011 to February 2007. Standardized diagnostic interviews and measures of depression, suicidal ideation, related psychopathology and level of functioning were periodically administered. Remission was defined as ≥ 3 weeks with ≤ 1 clinically significant symptom and no associated functional impairment (score of 1 on the adolescent version of the Longitudinal Interval Follow-Up Evaluation [A-LIFE], and relapse as ≥ 2 weeks with probable or definite depressive disorder (score of 3 or 4 on the A-LIFE). Mixed effects regression models were applied to estimate remission, relapse, and functional recovery. Results By 72 weeks, an estimated 61.1% of the randomized youths had reached remission. Randomly assigned treatment (first 12 weeks) did not influence remission rate or time to remission, but the group assigned to SSRI's had a more rapid decline in self-reported depressive symptoms and suicidal ideation than those assigned to venlafaxine (p<.05). Participants with more severe depression, greater dysfunction, and alcohol/drug use at baseline were less likely to remit. The depressive symptom trajectory of the remitters diverged from that of non-remitters by the first 6 weeks of treatment (p<.001). Of the 130 participants in remission at week 24, 25.4% relapsed in

  14. 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. Copyright © 2016 Elsevier Inc. All rights reserved.

  15. 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

  16. 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.

  17. 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.

  18. [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.

  19. 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.

  20. 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.

  1. 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

  2. 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

  3. 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

  4. 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.

  5. 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 reservoir...

  6. 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.

  7. 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

  8. 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…

  9. 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…

  10. 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…

  11. 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…

  12. 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…

  13. 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…

  14. Long-term no-tillage and organic input management enhanced the diversity and stability of soil microbial community.

    PubMed

    Wang, Yi; Li, Chunyue; Tu, Cong; Hoyt, Greg D; DeForest, Jared L; Hu, Shuijin

    2017-12-31

    Intensive tillage and high inputs of chemicals are frequently used in conventional agriculture management, which critically depresses soil properties and causes soil erosion and nonpoint source pollution. Conservation practices, such as no-tillage and organic farming, have potential to enhance soil health. However, the long-term impact of no-tillage and organic practices on soil microbial diversity and community structure has not been fully understood, particularly in humid, warm climate regions such as the southeast USA. We hypothesized that organic inputs will lead to greater microbial diversity and a more stable microbial community, and that the combination of no-tillage and organic inputs will maximize soil microbial diversity. We conducted a long-term experiment in the southern Appalachian mountains of North Carolina, USA to test these hypotheses. The results showed that soil microbial diversity and community structure diverged under different management regimes after long term continuous treatments. Organic input dominated the effect of management practices on soil microbial properties, although no-tillage practice also exerted significant impacts. Both no-tillage and organic inputs significantly promoted soil microbial diversity and community stability. The combination of no-tillage and organic management increased soil microbial diversity over the conventional tillage and led to a microbial community structure more similar to the one in an adjacent grassland. These results indicate that effective management through reducing tillage and increasing organic C inputs can enhance soil microbial diversity and community stability. Copyright © 2017 Elsevier B.V. All rights reserved.

  15. Long-Term Impact of a Cell Phone-Enhanced Parenting Intervention.

    PubMed

    Lefever, Jennifer E Burke; Bigelow, Kathryn M; Carta, Judith J; Borkowski, John G; Grandfield, Elizabeth; McCune, Luke; Irvin, Dwight W; Warren, Steven F

    2017-01-01

    Home visiting programs support positive parenting in populations at-risk of child maltreatment, but their impact is often limited by poor retention and engagement. The current study assessed whether a cellular phone-supported version (PCI-C) of the Parent-Child Interactions (PCI) intervention improved long-term parenting practices, maternal depression, and children's aggression. Low-income mothers ( n = 371) of preschool-aged children were assigned to one of the three groups: PCI-C, PCI, and a wait-list control (WLC) group. Parenting improved in both intervention groups between baseline and 12-month follow-up compared to the WLC. Children in the PCI-C group were rated to be more cooperative and less aggressive than children in the WLC. The results offer evidence of the long-term effectiveness of PCI and the additional benefits of cellular phone supports for promoting intervention retention and improving children's behavior.

  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. Effectiveness of long-term vortioxetine treatment of patients with major depressive disorder.

    PubMed

    Vieta, Eduard; Loft, Henrik; Florea, Ioana

    2017-09-01

    To investigate the effectiveness, safety, and tolerability of vortioxetine in patients treated at therapeutic doses (5-20mg/day) for both acute and maintenance treatment, patient-level data were pooled from 5 long-term (52-week), open-label extension studies of major depressive disorder. The mean (±standard deviation) MADRS total score improved from 17.1±10.2 at the start of maintenance therapy to 7.6±8.2 (observed cases [OC]) or 10.3±9.9 (last observation carried forward [LOCF]) at week 52. The mean HAM-A total scores improved from 11.3±6.9 to 6.0±6.0 (OC) or 7.5±6.7 (LOCF) and the mean CGI-S score improved from 3.11±1.20 to 1.94±1.08 (OC) or 2.27±1.26 (LOCF) at week 52. Response and remission rates increased over time. At week 52, the total response rate was 75.4% (n=916/1215, LOCF) and the total remission rate was 60.7% (n=738/1215, LOCF). There were no differences in effectiveness as assessed by MADRS total scores at week 52 in subgroups based on gender, age (<55 vs ≥55 years), baseline HAM-A total score (<20 vs ≥20), baseline MADRS total score (<30 vs ≥30), previous major depressive episodes (MDEs) (<3 vs ≥3) or current MDE duration (<6 vs ≥6 months) at the start of the lead-in studies, or response status (≥50% decrease in MADRS total score during the lead-in study). The most commonly reported adverse event during the maintenance period was nausea. Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.

  19. A stochastic signaling network mediates the probabilistic induction of cerebellar long-term depression.

    PubMed

    Antunes, Gabriela; De Schutter, Erik

    2012-07-04

    Many cellular processes involve a small number of molecules and undergo stochastic fluctuations in their levels of activity. Cerebellar long-term depression (LTD) is a form of synaptic plasticity expressed as a reduction in the number of synaptic AMPA receptors (AMPARs) in Purkinje cells. We developed a stochastic model of the LTD signaling network, including a PKC-ERK-cPLA(2) positive feedback loop and mechanisms of AMPAR trafficking, and tuned the model to replicate calcium uncaging experiments. The signaling network activity in single synapses switches between two discrete stable states (LTD and non-LTD) in a probabilistic manner. The stochasticity of the signaling network causes threshold dithering and allows at the macroscopic level for many different and stable mean magnitudes of depression. The probability of LTD occurrence in a single spine is only modulated by the concentration and duration of the signal used to trigger it, and inputs with the same magnitude can give rise to two different responses; there is no threshold for the input signal. The stochasticity is intrinsic to the signaling network and not mostly dependent on noise in the calcium input signal, as has been suggested previously. The activities of the ultrasensitive ERK and of cPLA(2) undergo strong stochastic fluctuations. Conversely, PKC, which acts as a noise filter, is more constantly activated. Systematic variation of the biochemical population size demonstrates that threshold dithering and the absence of spontaneous LTD depend critically on the number of molecules in a spine, indicating constraints on spine size in Purkinje cells.

  20. 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.

  1. 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.

  2. Nicotine Uses Neuron-Glia Communication to Enhance Hippocampal Synaptic Transmission and Long-term Memory

    PubMed Central

    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. PMID:23185511

  3. Talking about depression: a qualitative study of barriers to managing depression in people with long term conditions in primary care.

    PubMed

    Coventry, Peter A; Hays, Rebecca; Dickens, Chris; Bundy, Christine; Garrett, Charlotte; Cherrington, Andrea; Chew-Graham, Carolyn

    2011-03-22

    The risk of depression is increased in people with long term conditions (LTCs) and is associated with poorer patient outcomes for both the depressive illness and the LTC, but often remains undetected and poorly managed. The aim of this study was to identify and explore barriers to detecting and managing depression in primary care in people with two exemplar LTCs: diabetes and coronary heart disease (CHD). Qualitative in-depth interviews were conducted with 19 healthcare professionals drawn predominately from primary care, along with 7 service users and 3 carers (n = 29). One focus group was then held with a set of 6 healthcare professionals and a set of 7 service users and 1 carer (n = 14). Interviews and the focus group were digitally recorded, transcribed verbatim, and analysed independently. The two data sets were then inspected for commonalities using a constant comparative method, leading to a final thematic framework used in this paper. Barriers to detecting and managing depression in people with LTCs in primary care exist: i) when practitioners in partnership with patients conceptualise depression as a common and understandable response to the losses associated with LTCs - depression in the presence of LTCs is normalised, militating against its recognition and treatment; ii) where highly performanced managed consultations under the terms of the Quality and Outcomes Framework encourage reductionist approaches to case-finding in people with CHD and diabetes, and iii) where there is uncertainty among practitioners about how to negotiate labels for depression in people with LTCs in ways that might facilitate shared understanding and future management. Depression was often normalised in the presence of LTCs, obviating rather than facilitating further assessment and management. Furthermore, structural constraints imposed by the QOF encouraged reductionist approaches to case-finding for depression in consultations for CHD and diabetes. Future work might focus on

  4. Factors Associated with Depression Assessed by the Patient Health Questionnaire-2 in Long-Term Cancer Survivors.

    PubMed

    Goo, Ae-Jin; Song, Yun-Mi; Shin, Jinyoung; Ko, Hyeonyoung

    2016-07-01

    This cross-sectional study aimed to evaluate the prevalence of depressive disorders and factors associated in long-term cancer survivors. A total of 702 long-term cancer survivors over 5-years in remission were recruited in a university-affiliated tertiary hospital in Korea. Self-report using the Patient Health Questionnaire-2 and the Fatigue Severity Scale assessed depression and fatigue, respectively. Demographic characteristics, cancer-related clinical characteristics, comorbidity, health behaviors, and physical symptoms were assessed through the review of medical records or a structured self-administered questionnaire. We identified 26.1% of patients who had a depressed mood or displayed a loss of interest. The most prevalent primary site of cancer was the stomach (65.2%), followed by lung, breast, colorectal, and thyroid cancer. We also found that 5.7% of subjects experienced double or triple primary cancers. Larger proportion among depressive group (89.1%) complained at least one physical problem than among non-depressive group (53.2%). Physical symptoms including sleep problems, dry mouth, indigestion, pain, decreased appetite, and febrile sense were more frequent in the depressive group than in the non-depressive group. The Fatigue Severity Scale scores were higher in the depressive group than in the non-depressive group (P<0.001). Multiple logistic regression analysis showed that the highest tertile level of fatigue (odds ratio, 7.31; 95% confidence interval, 3.81-14.02) was associated with the increased risk of depression. These findings suggest that careful concern about depression is necessary in long-term cancer survivors. Fatigue may be a surrogate sign for depression, and warrants further evaluation.

  5. 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.

  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. 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…

  8. 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…

  9. 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…

  10. 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…

  11. 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…

  12. 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…

  13. Long-term effectiveness of collaborative depression care in older primary care patients with and without PTSD symptoms.

    PubMed

    Chan, Domin; Fan, Ming-Yu; Unützer, Jürgen

    2011-07-01

    Depressed patients with comorbid post-traumatic stress disorder (PTSD) are more functionally impaired and may take longer to respond to depression treatment than patients without PTSD. This study examined the long-term effects of PTSD on depression severity, treatment response, and health care costs among older adults. Patients were recruited from 18 primary care clinics in five states. A total of 1801 patients aged 60 years or older with major depression or dysthymia were randomized to Improving Mood Promoting Access to Collaborative Treatment (IMPACT) collaborative care or usual care. The study included 191 (10.6%) subjects who screened positive for PTSD. Depression severity, assessed by the Hopkins Depression Symptom Checklist, was used to estimate depression-free days (DFDs) over 24 months. Total health care costs included inpatient, outpatient, and pharmacy costs. Depressed patients with PTSD had higher depression severity than patients without PTSD symptoms at baseline. Over 2 years, intervention patients with PTSD symptoms had relatively the same benefits from collaborative care (99 more DFDs than usual care patients) as patients without PTSD (108 more DFDs than usual care) (p = 0.85). Total health care costs did not differ significantly for depressed patients with and without PTSD symptoms. Depressed older adults with PTSD symptoms were more depressed at baseline, but collaborative care (compared to usual care) produced similar improvements in depression severity in both groups. This reduction of depression symptoms was observed for up to 12 months after the intervention ended, suggesting that long-term improvements in depression are possible with collaborative care in patients with and without PTSD symptoms. Copyright © 2010 John Wiley & Sons, Ltd.

  14. Ethanol acutely modulates mGluR1-dependent long-term depression in cerebellum.

    PubMed

    Su, Li-Da; Sun, Cheng-Long; Shen, Ying

    2010-07-01

    Acute and chronic ethanol exposure produces profound impairments in motor functioning. Individuals with lower sensitivity to the acute motor impairing effects of ethanol have an increased risk of developing alcohol dependence and abuse, and infants with subtle delays in motor coordination development may have an increased risk for subsequently developing alcoholism. Thus, understanding the mechanism by which ethanol disrupts motor functioning is very important. Parasagittal slices of the cerebellar vermis (250 microM thick) were prepared from P17 to 20 Sprague-Dawley rats. Whole-cell recordings of Purkinje cells were obtained with an Axopatch 200B amplifier. Parallel fiber-Purkinje cell synaptic currents were sampled at 1 kHz and digitized at 10 kHz, and synaptic long-term depression (LTD) was observed in either external or internal application of ethanol for comparison. We determined whether ethanol acutely affects parallel fiber LTD using whole-cell patch-clamp recordings from Purkinje cells. Application of ethanol both externally (50 mM) and internally (17 and 10 mM) significantly suppressed mGluR-mediate slow currents. Short-term external ethanol exposure (50 but not 17 mM) during tetanus blocked mGluR-dependent parallel fiber LTD. Furthermore, internal 17 and 10 mM ethanol completely inhibited this LTD. The results of the current study demonstrate that ethanol acutely suppresses parallel fiber LTD and may influence the mGluR-mediated slow current intracellularly. This study, plus previous evidence by Carta and colleagues (2006) and Belmeguenai and colleagues (2008), suggests significant actions of ethanol on mGluR-mediated currents and its dependent plasticity in brain.

  15. Nitric Oxide Regulates Input Specificity of Long-Term Depression and Context Dependence of Cerebellar Learning

    PubMed Central

    Ogasawara, Hideaki; Doi, Tomokazu; Doya, Kenji; Kawato, Mitsuo

    2007-01-01

    Recent studies have shown that multiple internal models are acquired in the cerebellum and that these can be switched under a given context of behavior. It has been proposed that long-term depression (LTD) of parallel fiber (PF)–Purkinje cell (PC) synapses forms the cellular basis of cerebellar learning, and that the presynaptically synthesized messenger nitric oxide (NO) is a crucial “gatekeeper” for LTD. Because NO diffuses freely to neighboring synapses, this volume learning is not input-specific and brings into question the biological significance of LTD as the basic mechanism for efficient supervised learning. To better characterize the role of NO in cerebellar learning, we simulated the sequence of electrophysiological and biochemical events in PF–PC LTD by combining established simulation models of the electrophysiology, calcium dynamics, and signaling pathways of the PC. The results demonstrate that the local NO concentration is critical for induction of LTD and for its input specificity. Pre- and postsynaptic coincident firing is not sufficient for a PF–PC synapse to undergo LTD, and LTD is induced only when a sufficient amount of NO is provided by activation of the surrounding PFs. On the other hand, above-adequate levels of activity in nearby PFs cause accumulation of NO, which also allows LTD in neighboring synapses that were not directly stimulated, ruining input specificity. These findings lead us to propose the hypothesis that NO represents the relevance of a given context and enables context-dependent selection of internal models to be updated. We also predict sparse PF activity in vivo because, otherwise, input specificity would be lost. PMID:17222054

  16. 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

  17. 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. © 2015 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.

  18. 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.

  19. Developmental shift from long-term depression to long-term potentiation in the rat medial vestibular nuclei: role of group I metabotropic glutamate receptors

    PubMed Central

    Puyal, Julien; Grassi, Silvarosa; Dieni, Cristina; Frondaroli, Adele; Demêmes, Danielle; Raymond, Jaqueline; Pettorossi, Vito Enrico

    2003-01-01

    The effects of high frequency stimulation (HFS) of the primary vestibular afferents on synaptic transmission in the ventral part of the medial vestibular nuclei (vMVN) were studied during postnatal development and compared with the changes in the expression of the group I metabotropic glutamate receptor (mGluR) subtypes, mGluR1 and mGluR5. During the first stages of development, HFS always induced a mGluR5- and GABAA-dependent long-term depression (LTD) which did not require NMDA receptor and mGluR1 activation. The probability of inducing LTD decreased progressively throughout the development and it was zero at about the end of the second postnatal week. Conversely, long-term potentiation (LTP) appeared at the beginning of the second week and its occurrence increased to reach the adult value at the end of the third week. Of interest, the sudden change in the LTP frequency occurred at the time of eye opening, about the end of the second postnatal week. LTP depended on NMDA receptor and mGluR1 activation. In parallel with the modifications in synaptic plasticity, we observed that the expression patterns and localizations of mGluR5 and mGluR1 in the medial vestibular nuclei (MVN) changed during postnatal development. At the earlier stages the mGluR1 expression was minimal, then increased progressively. In contrast, mGluR5 expression was initially high, then decreased. While mGluR1 was exclusively localized in neuronal compartments and concentrated at the postsynaptic sites at all stages observed, mGluR5 was found mainly in neuronal compartments at immature stages, then preferentially in glial compartments at mature stages. These results provide the first evidence for a progressive change from LTD to LTP accompanied by a distinct maturation expression of mGluR1 and mGluR5 during the development of the MVN. PMID:12972627

  20. 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

  1. 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.

  2. 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

  3. Ethanol attenuation of long-term depression in the nucleus accumbens can be overcome by activation of TRPV1 receptors.

    PubMed

    Renteria, Rafael; Jeanes, Zachary M; Morrisett, Richard A

    2014-11-01

    Altered expression of synaptic plasticity within the nucleus accumbens (NAc) constitutes a critical neuroadaptive response to ethanol (EtOH) and other drugs of abuse. We have previously reported that N-methyl-D-aspartate receptor (NMDAR)-dependent long-term depression (LTD) is markedly affected by chronic intermittent ethanol exposure in vivo; however, endocannabinoid (eCB)-dependent synaptic depression, despite being very well-documented in the dorsal striatum, is much less well understood in the NAc. Whole cell patch clamp electrophysiology was used to investigate interactions between these different plasticity-induction systems. Excitatory postsynaptic currents (EPSCs) were measured in the NAc shell and NMDAR-LTD was induced by a pairing protocol (500 stimuli at 1 Hz stimulation [low-frequency stimulation (LFS)] paired with postsynaptic depolarization to -50 mV). AM251, a CB1 receptor antagonist, was used to determine whether this form of LTD is modulated by eCBs. To determine the effect of EtOH on a purely eCB-dependent response in the NAc, depolarization-induced suppression of excitation (DSE) was used in the presence of 40 mM EtOH. Finally, we determined whether the enhancement of eCB signaling with URB597, a fatty acid amide hydrolase inhibitor, and AM404, an anandamide re-uptake inhibitor would also modulate LFS LTD in the presence of NMDAR blockade or EtOH. In the presence of AM251, the LFS pairing protocol resulted in NMDAR-dependent long-term potentiation that was blocked with either EtOH or DL-APV. We also found that DSE in the NAc shell was blocked by AM251 and suppressed by EtOH. Enhanced eCB signaling rescued NAc-LTD expression in the presence of EtOH through a distinct mechanism requiring activation of TRPV1 receptors. EtOH modulation of synaptic plasticity in the NAc is dependent upon a complex interplay between NMDARs, eCBs, and TRPV1 receptors. These findings demonstrate a novel form of TRPV1-dependent LTD in the NAc shell that may be critical

  4. Enhanced Dentate Neurogenesis after Brain Injury Undermines Long-Term Neurogenic Potential and Promotes Seizure Susceptibility.

    PubMed

    Neuberger, Eric J; Swietek, Bogumila; Corrubia, Lucas; Prasanna, Anagha; Santhakumar, Vijayalakshmi

    2017-09-12

    Hippocampal dentate gyrus is a focus of enhanced neurogenesis and excitability after traumatic brain injury. Increased neurogenesis has been proposed to aid repair of the injured network. Our data show that an early increase in neurogenesis after fluid percussion concussive brain injury is transient and is followed by a persistent decrease compared with age-matched controls. Post-injury changes in neurogenesis paralleled changes in neural precursor cell proliferation and resulted in a long-term decline in neurogenic capacity. Targeted pharmacology to restore post-injury neurogenesis to control levels reversed the long-term decline in neurogenic capacity. Limiting post-injury neurogenesis reduced early increases in dentate excitability and seizure susceptibility. Our results challenge the assumption that increased neurogenesis after brain injury is beneficial and show that early post-traumatic increases in neurogenesis adversely affect long-term outcomes by exhausting neurogenic potential and enhancing epileptogenesis. Treatments aimed at limiting excessive neurogenesis can potentially restore neuroproliferative capacity and limit epilepsy after brain injury. Copyright © 2017 The Author(s). Published by Elsevier Inc. All rights reserved.

  5. Bacopa monnieri extract enhances learning-dependent hippocampal long-term synaptic potentiation.

    PubMed

    Promsuban, Charkriya; Limsuvan, Suveerawan; Akarasereenont, Pravit; Tilokskulchai, Kanokwan; Tapechum, Sompol; Pakaprot, Narawut

    2017-11-08

    Bacopa monnieri has been used in Ayurvedic medicine as a memory enhancer for a long time; however, its direct effect on synaptic plasticity has not been investigated. To the best of our knowledge, this study is the first to report the effect of B. monnieri on long-term synaptic potentiation in acute hippocampal slices. Adult male Wistar rats were orally administered either sterile water or the ethanolic extract of B. monnieri for 60 days. The extracellular recording was performed to measure the field excitatory postsynaptic potential in the acute hippocampal slices of these rats. Our results showed that B. monnieri extract significantly increased long-term potentiation magnitude compared with the control group, whereas there was no change in basal synaptic transmission. The data support the beneficial mnemonic effect of B. monnieri, and suggest that this effect might be because of the increase of learning-associated synaptic machinery, resulting in the long-term potentiation enhancement and strengthening of hippocampal synapses, which plays a critical role in learning and memory formation.

  6. 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.

  7. 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.

  8. Forebrain NR2B overexpression facilitating the prefrontal cortex long-term potentiation and enhancing working memory function in mice.

    PubMed

    Cui, Yihui; Jin, Jing; Zhang, Xuliang; Xu, Hao; Yang, Liguo; Du, Dan; Zeng, Qingwen; Tsien, Joe Z; Yu, Huiting; Cao, Xiaohua

    2011-01-01

    Prefrontal cortex plays an important role in working memory, attention regulation and behavioral inhibition. Its functions are associated with NMDA receptors. However, there is little information regarding the roles of NMDA receptor NR2B subunit in prefrontal cortical synaptic plasticity and prefrontal cortex-related working memory. Whether the up-regulation of NR2B subunit influences prefrontal cortical synaptic plasticity and working memory is not yet clear. In the present study, we measured prefrontal cortical synaptic plasticity and working memory function in NR2B overexpressing transgenic mice. In vitro electrophysiological data showed that overexpression of NR2B specifically in the forebrain region resulted in enhancement of prefrontal cortical long-term potentiation (LTP) but did not alter long-term depression (LTD). The enhanced LTP was completely abolished by a NR2B subunit selective antagonist, Ro25-6981, indicating that overexpression of NR2B subunit is responsible for enhanced LTP. In addition, NR2B transgenic mice exhibited better performance in a set of working memory paradigms including delay no-match-to-place T-maze, working memory version of water maze and odor span task. Our study provides evidence that NR2B subunit of NMDA receptor in prefrontal cortex is critical for prefrontal cortex LTP and prefrontal cortex-related working memory.

  9. 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

  10. 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.

  11. Presynaptic D2 dopamine receptors control long-term depression expression and memory processes in the temporal hippocampus.

    PubMed

    Rocchetti, Jill; Isingrini, Elsa; Dal Bo, Gregory; Sagheby, Sara; Menegaux, Aurore; Tronche, François; Levesque, Daniel; Moquin, Luc; Gratton, Alain; Wong, Tak Pan; Rubinstein, Marcelo; Giros, Bruno

    2015-03-15

    Dysfunctional mesocorticolimbic dopamine signaling has been linked to alterations in motor and reward-based functions associated with psychiatric disorders. Converging evidence from patients with psychiatric disorders and use of antipsychotics suggests that imbalance of dopamine signaling deeply alters hippocampal functions. However, given the lack of full characterization of a functional mesohippocampal pathway, the precise role of dopamine transmission in memory deficits associated with these disorders and their dedicated therapies is unknown. In particular, the positive outcome of antipsychotic treatments, commonly antagonizing D2 dopamine receptors (D2Rs), on cognitive deficits and memory impairments remains questionable. Following pharmacologic and genetic manipulation of dopamine transmission, we performed anatomic, neurochemical, electrophysiologic, and behavioral investigations to uncover the role of D2Rs in hippocampal-dependent plasticity and learning. Naïve mice (n = 4-21) were used in the different procedures. Dopamine modulated both long-term potentiation and long-term depression in the temporal hippocampus as well as spatial and recognition learning and memory in mice through D2Rs. Although genetic deletion or pharmacologic blockade of D2Rs led to the loss of long-term potentiation expression, the specific genetic removal of presynaptic D2Rs impaired long-term depression and performances on spatial memory tasks. Presynaptic D2Rs in dopamine fibers of the temporal hippocampus tightly modulate long-term depression expression and play a major role in the regulation of hippocampal learning and memory. This direct role of mesohippocampal dopamine input as uncovered here adds a new dimension to dopamine involvement in the physiology underlying deficits associated with neuropsychiatric disorders. Copyright © 2015 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

  12. Socio-demographic factors and long-term use of benzodiazepines in patients with depression, anxiety or insomnia.

    PubMed

    Sjöstedt, Cecilia; Ohlsson, Henrik; Li, Xinjun; Sundquist, Kristina

    2017-03-01

    Former studies that have attempted to characterize individual socio-demographic factors associated with long-term benzodiazepine use were based on relatively small sample sizes and/or self-reported data. Our aim was to clarify this using large-scale primary health care data from Sweden. The present study covered 71 primary health care centres containing individual-level data from a total of 919, 941 individuals who visited a primary health care centre (PHCC) during the period 2001-2007. From this database we selected individuals 25 years or older with depression, anxiety and/or insomnia and who were prescribed a benzodiazepine within 0-90 as well as 91-270 days after their first clinical diagnosis of depression, anxiety and/or insomnia. Older age (OR, 2.92, 95% CI, 2.28-3.84), middle SES (OR, 1.22, 95% CI, 1.08-1.38), being on social welfare (OR, 1.40, 95% CI, 1.23-1.62) and not being married were associated with higher long-term benzodiazepine use. The PHCCs only explained a small part of the individual variation in long-term benzodiazepine use. Awareness of the impact on long-term benzodiazepine use of certain individual-level socio-demographic factors is important for health care workers and decision-makers who should aim at targeting general interventions at all primary health care centres. Copyright © 2017 Elsevier Ireland Ltd. All rights reserved.

  13. 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.

  14. Upregulation of CREB-mediated transcription enhances both short- and long-term memory.

    PubMed

    Suzuki, Akinobu; Fukushima, Hotaka; Mukawa, Takuya; Toyoda, Hiroki; Wu, Long-Jun; Zhao, Ming-Gao; Xu, Hui; Shang, Yuze; Endoh, Kengo; Iwamoto, Taku; Mamiya, Nori; Okano, Emiko; Hasegawa, Shunsuke; Mercaldo, Valentina; Zhang, Yue; Maeda, Ryouta; Ohta, Miho; Josselyn, Sheena A; Zhuo, Min; Kida, Satoshi

    2011-06-15

    Unraveling the mechanisms by which the molecular manipulation of genes of interest enhances cognitive function is important to establish genetic therapies for cognitive disorders. Although CREB is thought to positively regulate formation of long-term memory (LTM), gain-of-function effects of CREB remain poorly understood, especially at the behavioral level. To address this, we generated four lines of transgenic mice expressing dominant active CREB mutants (CREB-Y134F or CREB-DIEDML) in the forebrain that exhibited moderate upregulation of CREB activity. These transgenic lines improved not only LTM but also long-lasting long-term potentiation in the CA1 area in the hippocampus. However, we also observed enhanced short-term memory (STM) in contextual fear-conditioning and social recognition tasks. Enhanced LTM and STM could be dissociated behaviorally in these four lines of transgenic mice, suggesting that the underlying mechanism for enhanced STM and LTM are distinct. LTM enhancement seems to be attributable to the improvement of memory consolidation by the upregulation of CREB transcriptional activity, whereas higher basal levels of BDNF, a CREB target gene, predicted enhanced shorter-term memory. The importance of BDNF in STM was verified by microinfusing BDNF or BDNF inhibitors into the hippocampus of wild-type or transgenic mice. Additionally, increasing BDNF further enhanced LTM in one of the lines of transgenic mice that displayed a normal BDNF level but enhanced LTM, suggesting that upregulation of BDNF and CREB activity cooperatively enhances LTM formation. Our findings suggest that CREB positively regulates memory consolidation and affects memory performance by regulating BDNF expression.

  15. Assessing efficacy/effectiveness and safety/tolerability profiles of adjunctive pramipexole in bipolar depression: acute versus long-term data.

    PubMed

    Dell'Osso, Bernardo; Ketter, Terence A

    2013-11-01

    Bipolar depression represents the most difficult-to-treat phase of bipolar disorder, mood-stabilizing compounds and second-generation antipsychotics being only partially effective, whereas the use of antidepressants is highly controversial because of risks of inefficacy, switching, rapid cycling, and increased suicidality. Among various augmentative pharmacological treatments, compounds with dopamine-enhancing activity have been shown to be variably beneficial in the treatment of bipolar depression with drug-resistance features. In particular, pramipexole - a dopamine D2/D3 receptor agonist - showed antidepressant properties in bipolar depressed patients in both randomized-controlled trials and open acute and follow-up reports. The present review aims to provide an updated perspective on the use of adjunctive pramipexole in bipolar depression, taking into account randomized-controlled trials, as well as open naturalistic studies, with a specific focus on the evaluation of acute versus long-term data in terms of effectiveness and tolerability. Despite methodological differences, short-term studies support the acute efficacy and tolerability/safety of adjunctive pramipexole, whereas open extended observations seem to confirm the effectiveness of the compound, with some additional concern in terms of safety and tolerability issues. Adjunctive pramipexole may be a valid option in both the acute and the long-term treatment of drug-resistant bipolar depression, with possible superior tolerability in the short term.

  16. 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.

  17. 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.

  18. 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

  19. Serotonin increases the incidence of primary afferent-evoked long-term depression in rat deep dorsal horn neurons.

    PubMed

    Garraway, S M; Hochman, S

    2001-05-01

    5-hydroxytryptamine (5-HT) is released in spinal cord by descending systems that modulate somatosensory transmission and can potently depress primary afferent-evoked synaptic responses in dorsal horn neurons. Since primary afferent activity-induced long-term potentiation (LTP) may contribute to central sensitization of nociception, we studied the effects of 5-HT on the expression of sensory-evoked LTP and long-term depression (LTD) in deep dorsal horn (DDH) neurons. Whole cell, predominantly current clamp, recordings were obtained from DDH neurons in transverse slices of neonatal rat lumbar spinal cord. The effect of 5-HT on dorsal-root stimulation-evoked synaptic responses was tested before, during, or after high-frequency conditioning stimulation (CS). In most cells (80%), 5-HT caused a depression of the naïve synaptic response. Even though 5-HT depressed evoked responses, CS in the presence of 5-HT was not only still capable of inducing LTD but also increased its incidence from 54% in controls to 88% (P < 0.001). Activation of ligands selective for 5-HT(1A/1B) and 5-HT(1B), but not 5-HT(2A/2C) or 5-HT(3) receptors, best reproduced these actions. 5-HT also potently depressed postconditioning synaptic responses regardless of whether the induced plasticity was LTP or LTD. Our results demonstrate that in addition to depressing the amplitude of evoked sensory input, 5-HT can also control the direction of its long-term modifiability, favoring the expression of LTD. These findings demonstrate cellular mechanisms that may contribute to the descending serotonergic control of nociception.

  20. Glibenclamide enhances neurogenesis and improves long-term functional recovery after transient focal cerebral ischemia

    PubMed Central

    Ortega, Francisco J; Jolkkonen, Jukka; Mahy, Nicole; Rodríguez, Manuel J

    2013-01-01

    Glibenclamide is neuroprotective against cerebral ischemia in rats. We studied whether glibenclamide enhances long-term brain repair and improves behavioral recovery after stroke. Adult male Wistar rats were subjected to transient middle cerebral artery occlusion (MCAO) for 90 minutes. A low dose of glibenclamide (total 0.6 μg) was administered intravenously 6, 12, and 24 hours after reperfusion. We assessed behavioral outcome during a 30-day follow-up and animals were perfused for histological evaluation. In vitro specific binding of glibenclamide to microglia increased after pro-inflammatory stimuli. In vivo glibenclamide was associated with increased migration of doublecortin-positive cells in the striatum toward the ischemic lesion 72 hours after MCAO, and reactive microglia expressed sulfonylurea receptor 1 (SUR1) and Kir6.2 in the medial striatum. One month after MCAO, glibenclamide was also associated with increased number of NeuN-positive and 5-bromo-2-deoxyuridine-positive neurons in the cortex and hippocampus, and enhanced angiogenesis in the hippocampus. Consequently, glibenclamide-treated MCAO rats showed improved performance in the limb-placing test on postoperative days 22 to 29, and in the cylinder and water-maze test on postoperative day 29. Therefore, acute blockade of SUR1 by glibenclamide enhanced long-term brain repair in MCAO rats, which was associated with improved behavioral outcome. PMID:23149556

  1. Long-term impact of intrauterine fetal death on quality of life and depression: a case-control study.

    PubMed

    Gravensteen, Ida Kathrine; Helgadottir, Linda Bjørk; Jacobsen, Eva-Marie; Sandset, Per Morten; Ekeberg, Øivind

    2012-06-07

    Intrauterine fetal death (IUFD) is a serious incidence that has been shown to impact mothers' psychological well-being in the short-term. Long-term quality of life (QOL) and depression after IUFD is not known. This study aimed to determine the association between intrauterine fetal death and long-term QOL, well-being, and depression. Analyses were performed on collected data among 106 women with a history of intrauterine fetal death (IUFD) and 262 women with live births, 5-18 years after the event. Univariable and multivariable linear and logistic regression models were used to quantify the association between previous fetal death and long-term QOL, well-being and depression. QOL was assessed using the QOL Index (QLI), symptoms of depression using the Center for Epidemiological Studies Depression Scale (CES-D), and subjective well-being using the General Health Questionnaire 20 (GHQ-20). More of the cases had characteristics associated with lower socioeconomic status and did not rate their health as good as did the controls. The QLI health and functioning subscale score was slightly but significantly lower in the cases than in the controls (22.3. vs 23.5, P = .023). The CES-D depressed affect subscale score (2.0 vs 1.0, P = 0.004) and the CES-D global score (7.4 vs 5.0, P = .017) were higher in the cases. Subjective well-being did not differ between groups (20.6 vs 19.4, P = .094). After adjusting for demographic and health-related variables, IUFD was not associated with global QOL (P = .674), subjective well-being (P = .700), or global depression score (adjusted odds ratio = 0.77, 95% confidence interval 0.37-1.57). Women with previous IUFD, of which the majority have received short-term interventions, share the same level of long-term QOL, well-being and global depression as women with live births only, when adjusted for possible confounders. The study was registered at http://www.clinicaltrials.gov, with registration number NCT 00856076.

  2. 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

  3. Long-Term Associations of Justice Sensitivity, Rejection Sensitivity, and Depressive Symptoms in Children and Adolescents

    PubMed Central

    Bondü, Rebecca; Sahyazici-Knaak, Fidan; Esser, Günter

    2017-01-01

    Depressive symptoms have been related to anxious rejection sensitivity, but little is known about relations with angry rejection sensitivity and justice sensitivity. We measured rejection sensitivity, justice sensitivity, and depressive symptoms in 1,665 9-to-21-year olds at two points of measurement. Participants with high T1 levels of depressive symptoms reported higher anxious and angry rejection sensitivity and higher justice sensitivity than controls at T1 and T2. T1 rejection, but not justice sensitivity predicted T2 depressive symptoms; high victim justice sensitivity, however, added to the stabilization of depressive symptoms. T1 depressive symptoms positively predicted T2 anxious and angry rejection and victim justice sensitivity. Hence, sensitivity toward negative social cues may be cause and consequence of depressive symptoms and requires consideration in cognitive-behavioral treatment of depression. PMID:28955257

  4. Effect of long-term exposure to air pollution on anxiety and depression in adults: A cross-sectional study.

    PubMed

    Vert, Cristina; Sánchez-Benavides, Gonzalo; Martínez, David; Gotsens, Xavier; Gramunt, Nina; Cirach, Marta; Molinuevo, José Luis; Sunyer, Jordi; Nieuwenhuijsen, Mark J; Crous-Bou, Marta; Gascon, Mireia

    2017-08-01

    The association between exposure to air pollutants and mental disorders among adults has been suggested, although results are not consistent. To analyze the association between long-term exposure to air pollution and history of anxiety and depression disorders and of medication use (benzodiazepines and antidepressants) in adults living in Barcelona. A total of 958 adults (45-74 years old) residents in Barcelona, most of them having at least one of their parents diagnosed with dementia (86%), and participating in the ALFA (Alzheimer and Families) study, were included. We used Land Use Regression (LUR) models to estimate long-term residential exposure (period 2009-2014) to PM2.5, PM2.5 absorbance (PM2.5 abs), PM10, PM coarse, NO2 and NOx. Between 2013 and 2014 participants self-reported their history of anxiety and depression disorders and related medication use. The analysis was focused on those participants reporting outcome occurrence from 2009 onwards (until 2014). We observed an increased odds of history of depression disorders with increasing concentrations of all air pollutants [e.g. an increased odds of depression of 2.00 (95% CI; 1.37, 2.93) for each 10μg/m(3) NO2 increase]. Such associations were consistent with an increased odds of medication use in relation to higher concentrations of air pollutants [e.g. an increased odds of antidepressants use of 1.23 (1.04, 1.44) for each 20μg/m(3) NOx increase]. Associations regarding anxiety disorders did not reach statistical significance. Our study shows that increasing long-term exposure to air pollution may increase the odds of depression and the use of antidepressants and benzodiazepines. Further studies are needed to replicate our results and confirm this association. Copyright © 2017 Elsevier GmbH. All rights reserved.

  5. Six-month outcomes of co-occurring delirium, depression, and dementia in long-term care.

    PubMed

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

    2014-12-01

    To describe the 6-month outcomes of co-occurring delirium (full syndrome and subsyndromal symptoms), depression, and dementia in a long-term care (LTC) population. Observational, prospective cohort study with 6-month follow-up conducted from 2005 to 2009. Seven LTC facilities in the province of Quebec, Canada. Newly admitted and long-term residents recruited consecutively from lists of residents aged 65 and older admitted for LTC, with stratification into groups with and without severe cognitive impairment. The study sample comprised 274 residents with complete data at baseline on delirium, dementia, and depression. Outcomes were 6-month mortality, functional decline (10-point decline from baseline on 100-point Barthel scale), and cognitive decline (3-point decline on 30-point Mini-Mental State Examination). Predictors included delirium (full syndrome or subsyndromal symptoms, using the Confusion Assessment Method), depression (Cornell Scale for Depression in Dementia), and dementia (chart diagnosis). The baseline prevalences of delirium, subsyndromal symptoms of delirium (SSD), depression, and dementia were 11%, 44%, 19%, and 66%, respectively. By 6 months, 10% of 274 had died, 19% of 233 had experienced functional decline, and 17% of 246 had experienced cognitive decline. An analysis using multivariable generalized linear models found the following significant interaction effects (P < .15): between depression and dementia for mortality, between delirium and depression for functional decline, and between SSD and dementia for cognitive decline. Co-occurrence of delirium, SSD, depression, and dementia in LTC residents appears to affect some 6-month outcomes. Because of limited statistical power, it was not possible to draw conclusions about the effects of the co-occurrence of some syndromes on poorer outcomes. © 2014, Copyright the Authors Journal compilation © 2014, The American Geriatrics Society.

  6. Music training causes long-term enhancement of preschool children's spatial-temporal reasoning.

    PubMed

    Rauscher, F H; Shaw, G L; Levine, L J; Wright, E L; Dennis, W R; Newcomb, R L

    1997-02-01

    Predictions from a structured cortical model led us to test the hypothesis that music training enhances young children's spatial-temporal reasoning. Seventy-eight preschool children participated in this study. Thirty-four children received private piano keyboard lessons, 20 children received private computer lessons, and 24 children provided other controls. Four standard, age-calibrated, spatial reasoning tests were given before and after training; one test assessed spatial-temporal reasoning and three tests assessed spatial recognition. Significant improvement on the spatial-temporal test was found for the keyboard group only. No group improved significantly on the spatial recognition tests. The magnitude of the spatial-temporal improvement from keyboard training was greater than one standard deviation of the standardized test and lasted at least one day, a duration traditionally classified as long term. This represents an increase in time by a factor of over 100 compared to a previous study in which listening to a Mozart piano sonata primed spatial-temporal reasoning in college students. This suggests that music training produces long-term modifications in underlying neural circuitry in regions not primarily concerned with music and might be investigated using EEG. We propose that an improvement of the magnitude reported may enhance the learning of standard curricula, such as mathematics and science, that draw heavily upon spatial-temporal reasoning.

  7. Long-Term Depressive Symptoms and Acculturative Stress Issues Among Immigrants From the Former Soviet Union.

    PubMed

    Baker, Cathy J

    2016-09-01

    Previous studies regarding depressive symptoms and acculturative stress among immigrants have been limited to the initial period after immigration. The relationships between depressive symptoms, acculturation, and acculturative stress among immigrants from the former Soviet Union were examined in this descriptive study. Eighty immigrants from the former Soviet Union who had immigrated within the past 20 years were recruited in various community locations. Participants (N = 80), including recent and longer residing immigrants, reported elevated depressive symptoms and acculturative stress. Acculturative stress predicted depressive symptoms, controlling for dominant culture (American) immersion. However, length of time in the United States was not associated with depressive symptoms, ethnic culture immersion, or acculturative stress. Our results suggest that elevated depressive symptoms are related to acculturative stress but are not confined to the initial adjustment period. Steps to decrease acculturative stress might help decrease depressive symptoms in immigrants regardless of the number of years lived in the United States. © The Author(s) 2016.

  8. Paradoxical enhancement of active cochlear mechanics in long-term administration of salicylate.

    PubMed

    Huang, Zhi-Wu; Luo, Yanyun; Wu, Zhanyuan; Tao, Zhezhang; Jones, Raleigh O; Zhao, Hong-Bo

    2005-04-01

    Aspirin (salicylate) is a common drug and frequently used long term in the clinic. It has been well documented that salicylate can cause reversible hearing loss and tinnitus and diminish outer hair cell (OHC) electromotility, which is capable of actively boosting the basilar membrane vibration and producing acoustic emission. However, aspirin's ototoxic mechanisms still remain largely unclear. In this experiment, the effects of long-term salicylate administration on cochlear hearing functions were investigated by measuring distortion product otoacoustic emissions (DPOAEs) in awake guinea pigs. A single injection of sodium salicylate (200 mg/kg) could reduce the amplitude of the cubic distortion product of 2f1-f2 within 2 h. The reduction was significant at 20-50 dB SPL stimulus levels and recovered after 8 h. However, following daily injections of sodium salicylate (200 mg/kg, b.i.d.), the distortion product of 2f1-f2 progressively increased. After injection for 14 days, the distortion product increased about 2-3.5 dB SPL. The increase rate was about 0.2 dB SPL/day. The DP-I/O function remained nonlinear. The increase was greater at 40-70 dB SPL primary sound intensities and reversible. After cessation of salicylate treatment for 4 wk, the increased distortion product returned to the initial normal levels. The rate of recovery was 0.1 dB SPL/day. In the control animals with saline injection, there was no change in DPOAEs. The data revealed that long-term administration of salicylate could paradoxically enhance active cochlear mechanics. The data also suggested that salicylate-induced tinnitus might be generated at the OHC level.

  9. 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

  10. Long term sertraline effects on neural structures in depressed and nondepressed adult female nonhuman primates.

    PubMed

    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

    2015-12-01

    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. 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 20 mg/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. 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×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. These observations suggest that SSRIs may differentially affect neural structures in depressed and nondepressed individuals. Copyright © 2015 Elsevier Ltd. All rights reserved.

  11. Involvement of cAMP-guanine nucleotide exchange factor II in hippocampal long-term depression and behavioral flexibility.

    PubMed

    Lee, Kyungmin; Kobayashi, Yuki; Seo, Hyunhyo; Kwak, Ji-Hye; Masuda, Akira; Lim, Chae-Seok; Lee, Hye-Ryeon; Kang, SukJae Joshua; Park, Pojeong; Sim, Su-Eon; Kogo, Naomi; Kawasaki, Hiroaki; Kaang, Bong-Kiun; Itohara, Shigeyoshi

    2015-06-24

    Guanine nucleotide exchange factors (GEFs) activate small GTPases that are involved in several cellular functions. cAMP-guanine nucleotide exchange factor II (cAMP-GEF II) acts as a target for cAMP independently of protein kinase A (PKA) and functions as a GEF for Rap1 and Rap2. Although cAMP-GEF II is expressed abundantly in several brain areas including the cortex, striatum, and hippocampus, its specific function and possible role in hippocampal synaptic plasticity and cognitive processes remain elusive. Here, we investigated how cAMP-GEF II affects synaptic function and animal behavior using cAMP-GEF II knockout mice. We found that deletion of cAMP-GEF II induced moderate decrease in long-term potentiation, although this decrease was not statistically significant. On the other hand, it produced a significant and clear impairment in NMDA receptor-dependent long-term depression at the Schaffer collateral-CA1 synapses of hippocampus, while microscopic morphology, basal synaptic transmission, and depotentiation were normal. Behavioral testing using the Morris water maze and automated IntelliCage system showed that cAMP-GEF II deficient mice had moderately reduced behavioral flexibility in spatial learning and memory. We concluded that cAMP-GEF II plays a key role in hippocampal functions including behavioral flexibility in reversal learning and in mechanisms underlying induction of long-term depression.

  12. 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

  13. 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.

  14. 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.

  15. 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

  16. Effects of long-term sertraline treatment and depression on coronary artery atherosclerosis in premenopausal female primates.

    PubMed

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

    2015-04-01

    Major depressive disorder and coronary heart disease often co-occur in the same individuals. Selective serotonin reuptake inhibitors (SSRIs) are widely prescribed for depression and other disorders, but their effects on coronary heart disease risk remain unclear. We determined the effects of an SSRI on coronary artery atherosclerosis (CAA) in an established nonhuman primate model used to clarify the association between depression and CAA. Forty-two adult female cynomolgus macaques consuming a Western diet were characterized during an 18-month pretreatment phase and assigned to SSRI (sertraline hydrochloride 20 mg/kg, per os, once a 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. Before and during treatment, depressed monkeys had lower BW, body mass index, and plasma high-density lipoprotein cholesterol, and higher heart rates during the pretreatment (p < .01) but not the treatment phase (p = .17). There were no pretreatment differences between the sertraline and placebo groups. Sertraline reduced anxious behavior but had no effect on BW, body mass index, 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 in nondepressed monkeys (p < .036), and in sertraline than in placebo-treated monkeys (p = .040). The observed CAA extent in depressed monkeys treated with sertraline was 4.9 times higher than that in untreated depressed monkeys, and 6.5 times higher than that in nondepressed monkeys, on average. Depressed animals developed more CAA, and long-term treatment with sertraline resulted in more extensive CAA.

  17. Low depressive symptom and mental distress scores in adult long-term survivors of childhood acute lymphoblastic leukemia.

    PubMed

    Harila, Marika J; Niinivirta, Tomi I T; Winqvist, Satu; Harila-Saari, Arja H

    2011-04-01

    Childhood cancer survivors are thought to be at risk of psychological difficulties. We examined the prevalence of depressive symptoms and mental well-being in adult long-term survivors of childhood acute lymphoblastic leukemia (ALL) at a mean age of 20 years after the cessation of therapy. Depressive symptoms were assessed with Beck Depression Inventory (BDI-21) and mental distress with General Health Questionnaire (GHQ-12) among 73 ALL survivors and 146 healthy controls. The ALL survivors obtained significantly lower BDI scores (P=0.046) compared with the controls, indicating less depressive symptoms among the ALL survivors. BDI scores indicated a significantly less frequent moderate or severe depression in the ALL survivors compared with the controls (P=0.039). BDI scores indicated no depression in 80.8% of the ALL survivors and 73.3% of the control group. The female ALL survivors obtained lower BDI scores than did the female controls (P=0.005). No difference was found in GHQ-12 scores between the survivors and the controls. Survivors of ALL reported fewer depressive symptoms and equal mental well-being compared with healthy controls. Our findings support the idea that childhood leukemia survivors' subjective experience of well-being is possibly affected by repressive adaptive style.

  18. 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.

  19. Transcranial direct current stimulation (tDCS) enhances reconsolidation of long-term memory.

    PubMed

    Javadi, Amir Homayoun; Cheng, Paul

    2013-07-01

    A new and weak memory trace undergoes consolidation to gain resistance against interfering stimuli. When an encoded memory is recalled, it becomes labile and another round of consolidation, or reconsolidation, is required to restore its stability. Transcranial direct current stimulation (tDCS) is a non-invasive method of altering cortical excitability. The aim of this study was to examine the effects of tDCS on the reconsolidation of long-term verbal memory. Participants (n = 15) memorized words in the encoding session, then reactivated the memory of the words 3 h later using an old-new recognition task under anodal, cathodal and sham stimulation to the left dorsolateral prefrontal cortex (DLPFC). Finally, after another 5 h, they performed another round of the old-new recognition task and rated their confidence. Anodal tDCS during the second session resulted in significantly more words recognized in the third session as compared to cathodal and sham stimulation. Cathodal tDCS did not affect the recognition performance compared to sham stimulation. These results cannot be attributed to differences in response times and confidence ratings, as they were comparable in all conditions. In order to study whether the activation of a memory was crucial for the enhancing effects of anodal tDCS, a group of controls (n = 15) did not perform the recognition task in the second session but still underwent stimulation. Contrary to the main group, anodal stimulation did not enhance the memory performance for the control group. This result suggests that anodal tDCS over the left DLPFC can enhance the reconsolidation of long-term memory only when the memory has been reactivated. Copyright © 2013 Elsevier Inc. All rights reserved.

  20. Early Depressed mood after stroke predicts long-term disability: the Northern Manhattan Stroke Study (NOMASS)

    PubMed Central

    Willey, Joshua Z.; Disla, Norbelina; Moon, Yeseon Park; Paik, Myunghee C.; Sacco, Ralph L.; Boden-Albala, Bernadette; Elkind, Mitchell SV; Wright, Clinton

    2010-01-01

    Introduction Depression is highly prevalent after stroke, and may influence recovery. We aimed to determine whether depressed mood acutely after stroke predicts subsequent disability and mortality. Methods As part of the Northern Manhattan Stroke Study, a population-based incident stroke case follow-up study performed in a multiethnic urban population, participants were asked about depressed mood within 7–10 days after stroke. Participants were followed every 6 months the first 2 years, and yearly thereafter for 5 years, for death and disability measured by the Barthel Index (BI). We fitted polytomous logistic regression models using canonical link to examine the association between depressed mood after stroke and disability, comparing moderate (BI 60–95) and severe (BI < 60) disability to no disability (BI ≥ 95). Cox-proportional hazards models were created to examine the association between depressed mood and mortality. Results A question about depressed mood within 7–10 days after stroke was asked in 340 of 655 ischemic stroke patients enrolled, and 139 reported that they felt depressed. In multivariate analyses controlling for socio-demographic factors, stroke severity, and medical conditions, depressed mood was associated with a greater odds of severe disability compared to no disability at one (OR 2.91, 95% CI 1.07–7.91) and two years (OR 3.72, 95% CI 1.29–10.71) after stroke. Depressed mood was not associated with all cause mortality or vascular death. Conclusion Depressed mood after stroke is associated with disability but not mortality after stroke. Early screening and intervention for mood disorders after stroke may improve outcomes and requires further research. PMID:20671256

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

    PubMed

    Schuette, Sven R M; Fernández-Fernández, Diego; Lamla, Thorsten; Rosenbrock, Holger; Hobson, Scott

    2016-04-13

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

  2. Changes in prefrontal-limbic function in major depression after 15 months of long-term psychotherapy.

    PubMed

    Buchheim, Anna; Viviani, Roberto; Kessler, Henrik; Kächele, Horst; Cierpka, Manfred; Roth, Gerhard; George, Carol; Kernberg, Otto F; Bruns, Georg; Taubner, Svenja

    2012-01-01

    Neuroimaging studies of depression have demonstrated treatment-specific changes involving the limbic system and regulatory regions in the prefrontal cortex. While these studies have examined the effect of short-term, interpersonal or cognitive-behavioural psychotherapy, the effect of long-term, psychodynamic intervention has never been assessed. Here, we investigated recurrently depressed (DSM-IV) unmedicated outpatients (N = 16) and control participants matched for sex, age, and education (N = 17) before and after 15 months of psychodynamic psychotherapy. Participants were scanned at two time points, during which presentations of attachment-related scenes with neutral descriptions alternated with descriptions containing personal core sentences previously extracted from an attachment interview. Outcome measure was the interaction of the signal difference between personal and neutral presentations with group and time, and its association with symptom improvement during therapy. Signal associated with processing personalized attachment material varied in patients from baseline to endpoint, but not in healthy controls. Patients showed a higher activation in the left anterior hippocampus/amygdala, subgenual cingulate, and medial prefrontal cortex before treatment and a reduction in these areas after 15 months. This reduction was associated with improvement in depressiveness specifically, and in the medial prefrontal cortex with symptom improvement more generally. This is the first study documenting neurobiological changes in circuits implicated in emotional reactivity and control after long-term psychodynamic psychotherapy.

  3. Changes in Prefrontal-Limbic Function in Major Depression after 15 Months of Long-Term Psychotherapy

    PubMed Central

    Buchheim, Anna; Viviani, Roberto; Kessler, Henrik; Kächele, Horst; Cierpka, Manfred; Roth, Gerhard; George, Carol; Kernberg, Otto F.; Bruns, Georg; Taubner, Svenja

    2012-01-01

    Neuroimaging studies of depression have demonstrated treatment-specific changes involving the limbic system and regulatory regions in the prefrontal cortex. While these studies have examined the effect of short-term, interpersonal or cognitive-behavioural psychotherapy, the effect of long-term, psychodynamic intervention has never been assessed. Here, we investigated recurrently depressed (DSM-IV) unmedicated outpatients (N = 16) and control participants matched for sex, age, and education (N = 17) before and after 15 months of psychodynamic psychotherapy. Participants were scanned at two time points, during which presentations of attachment-related scenes with neutral descriptions alternated with descriptions containing personal core sentences previously extracted from an attachment interview. Outcome measure was the interaction of the signal difference between personal and neutral presentations with group and time, and its association with symptom improvement during therapy. Signal associated with processing personalized attachment material varied in patients from baseline to endpoint, but not in healthy controls. Patients showed a higher activation in the left anterior hippocampus/amygdala, subgenual cingulate, and medial prefrontal cortex before treatment and a reduction in these areas after 15 months. This reduction was associated with improvement in depressiveness specifically, and in the medial prefrontal cortex with symptom improvement more generally. This is the first study documenting neurobiological changes in circuits implicated in emotional reactivity and control after long-term psychodynamic psychotherapy. PMID:22470470

  4. Endocannabinoid-dependent long-term depression in a nociceptive synapse requires coordinated presynaptic and postsynaptic transcription and translation.

    PubMed

    Yuan, Sharleen; Burrell, Brian D

    2013-03-06

    Endocannabinoids (eCBs) play an important role in long-term regulation of synaptic signaling in both vertebrates and invertebrates. In this study, the role of transcription- and translation-dependent processes in presynaptic versus postsynaptic neurons was examined during eCB-mediated synaptic plasticity in the CNS of the leech. Low-frequency stimulation (LFS) of non-nociceptive afferents elicits eCB-dependent long-term depression (eCB-LTD) heterosynaptically in nociceptive synapses that lasts at least 2 h. Bath application of emetine, a protein synthesis inhibitor, blocked eCB-LTD after afferent LFS or exogenous eCB application, indicating that this depression was translation dependent. Bath application of actinomycin D, an irreversible RNA synthesis inhibitor, or 5,6-dichlorobenzimidazole 1-β-d-ribofurandoside (DRB), a reversible RNA synthesis inhibitor, also prevented eCB-LTD. Selective injection of DRB or emetine into the presynaptic or postsynaptic neuron before LFS indicated that eCB-LTD required transcription and translation in the postsynaptic neuron but only translation in the presynaptic cell. Depression observed immediately after LFS was also blocked when these transcription- and translation-dependent processes were inhibited. It is proposed that induction of eCB-LTD in this nociceptive synapse requires the coordination of presynaptic protein synthesis and postsynaptic mRNA and protein synthesis. These findings provide significant insights into both eCB-based synaptic plasticity and understanding how activity in non-nociceptive afferents modulates nociceptive pathways.

  5. 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

  6. 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. Copyright © 2015 IBRO. Published by Elsevier Ltd. All rights reserved.

  7. 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.

  8. 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.

  9. The mediating effects of depressive symptoms on nutritional status of older adults in long-term care facilities.

    PubMed

    Li, I-C; Kuo, H-T; Lin, Y-C

    2013-07-01

    To test whether depressive symptoms mediate the effects of activities of daily living (ADLs) on nutritional status of older adults living in long-term care (LTC) facilities in Taiwan. A cross-sectional study. Seventy-three community-based LTC facilities in northern Taiwan. This study sampled 306 adults ranging in age from 65 to 97 years who were free of acute infection or disease and who were able to communicate. Nutritional status was assessed by the Mini-Nutritional Assessment (MNA) scale and depressive symptoms were assessed by the short form of the Geriatric Depressive Scale (GDS-SF). MNA scores revealed that 65% of the subjects were at risk for malnutrition (17 to 23.5 points). In addition, depressive symptoms partially mediated the relationship between ADLs and nutritional status, with 10.7% of the effect of depressive symptoms on nutritional status going through the mediator. Interventions to reduce depressive symptoms among institutionalized older adults should focus on improving nutritional status rather than promoting ADLs, which are believed to be difficult to change.

  10. 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.

  11. 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…

  12. 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…

  13. Effects of anxiety on the long-term course of depressive disorders†

    PubMed Central

    Coryell, William; Fiedorowicz, Jess G.; Solomon, David; Leon, Andrew C.; Rice, John P.; Keller, Martin B.

    2012-01-01

    Background It is well established that the presence of prominent anxiety within depressive episodes portends poorer outcomes. Important questions remain as to which anxiety features are important to outcome and how sustained their prognostic effects are over time. Aims To examine the relative prognostic importance of specific anxiety features and to determine whether their effects persist over decades and apply to both unipolar and bipolar conditions. Method Participants with unipolar (n = 476) or bipolar (n = 335) depressive disorders were intensively followed for a mean of 16.7 years (s.d. = 8.5). Results The number and severity of anxiety symptoms, but not the presence of pre-existing anxiety disorders, showed a robust and continuous relationship to the subsequent time spent in depressive episodes in both unipolar and bipolar depressive disorder. The strength of this relationship changed little over five successive 5-year periods. Conclusions The severity of current anxiety symptoms within depressive episodes correlates strongly with the persistence of subsequent depressive symptoms and this relationship is stable over decades. PMID:21984801

  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. 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.

  16. Acute and long-term treatment of late-life major depressive disorder: duloxetine versus placebo.

    PubMed

    Robinson, Michael; Oakes, Tina Myers; Raskin, Joel; Liu, Peng; Shoemaker, Scarlett; Nelson, J Craig

    2014-01-01

    To compare the efficacy of duloxetine with placebo on depression in elderly patients with major depressive disorder. Multicenter, 24-week (12-week short-term and 12-week continuation), randomized, placebo-controlled, double-blind trial. United States, France, Mexico, Puerto Rico. Age 65 years or more with major depressive disorder diagnosis (one or more previous episode); Mini-Mental State Examination score ≥20; Montgomery-Asberg Depression Rating Scale total score ≥20. Duloxetine 60 or 120 mg/day or placebo; placebo rescue possible. Primary-Maier subscale of the 17-item Hamilton Depression Rating Scale (HAMD-17) at week 12. Secondary-Geriatric Depression Scale, HAMD-17 total score, cognitive measures, Brief Pain Inventory (BPI), Numeric Rating Scales (NRS) for pain, Clinical Global Impression-Severity scale, Patient Global Impression of Improvement in acute phase and acute plus continuation phase of treatment. Compared with placebo, duloxetine did not show significantly greater improvement from baseline on Maier subscale at 12 weeks, but did show significantly greater improvement at weeks 4, 8, 16, and 20. Similar patterns for Geriatric Depression Scale and Clinical Global Impression-Severity scale emerged, with significance also seen at week 24. There was a significant treatment effect for all BPI items and 4 of 6 NRS pain measures in the acute phase, most BPI items and half of the NRS measures in the continuation phase. More duloxetine-treated patients completed the study (63% versus 55%). A significantly higher percentage of duloxetine-treated patients versus placebo discontinued due to adverse event (15.3% versus 5.8%). Although the antidepressant efficacy of duloxetine was not confirmed by the primary outcome, several secondary measures at multiple time points suggested efficacy. Duloxetine had significant and meaningful beneficial effects on pain. Copyright © 2014 American Association for Geriatric Psychiatry. Published by Elsevier Inc. All rights

  17. 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.

  18. 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.

  19. 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.

  20. 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…

  1. 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…

  2. 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.

  3. 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…

  4. 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…

  5. Depression, pain, exposure to stressful life events, and long-term outcomes in temporomandibular disorder patients.

    PubMed

    Auerbach, S M; Laskin, D M; Frantsve, L M; Orr, T

    2001-06-01

    This study investigated the role of psychological factors in temporomandibular disorders (TMD). Orofacial pain patients' pretreatment levels of depression, disability caused by pain, and exposure to stressful life events were measured, and differences on these variables between temporomandibular joint (TMJ) disease patients and patients whose pain was of muscular origin (MPD) were evaluated. The use of these variables and patient diagnostic status in predicting response to treatment in a subsample of these patients was also evaluated. Before undergoing treatment, 258 patients were administered the Beck Depression Inventory (BDI), the Pain Disability Index (PDI), and the Social Readjustment Rating Scale (SRRS). Follow-up data on pain disability, current level of pain, depression, and satisfaction with treatment were obtained on 48 of these patients who were contacted at varying intervals after completing treatment. BDI scores obtained at the outset of treatment were significantly elevated and were positively correlated with SRRS and PDI scores. MPD patients had higher SRRS, BDI depression, and PDI pain disability scores than TMJ patients, and differences between the 2 groups in pain disability were greatest in areas that are often sources of interpersonal stress. Among follow-up patients, PDI scores declined after treatment, with MPD patients showing greater decreases than TMJ patients. Independent of patients' diagnostic status, their pretreatment PDI scores were predictive of their pain level at follow-up and were inversely related to their degree of satisfaction with treatment at follow-up; their pretreatment BDI scores were predictive of their depression level at follow-up. The findings are consistent with previous research indicating a link between emotional dysfunction and TMD and are largely supportive of the conclusion that psychological factors play a more pronounced role when pain is of muscular origin. Promising behavioral interventions are available for

  6. 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.

  7. Fatty-Acid Binding Proteins Modulate Sleep and Enhance Long-Term Memory Consolidation in Drosophila

    PubMed Central

    Gerstner, Jason R.; Vanderheyden, William M.; Shaw, Paul J.; Landry, Charles F.; Yin, Jerry C. P.

    2011-01-01

    Sleep is thought to be important for memory consolidation, since sleep deprivation has been shown to interfere with memory processing. However, the effects of augmenting sleep on memory formation are not well known, and testing the role of sleep in memory enhancement has been limited to pharmacological and behavioral approaches. Here we test the effect of overexpressing the brain-type fatty acid binding protein (Fabp7) on sleep and long-term memory (LTM) formation in Drosophila melanogaster. Transgenic flies carrying the murine Fabp7 or the Drosophila homologue dFabp had reduced baseline sleep but normal LTM, while Fabp induction produced increases in both net sleep and LTM. We also define a post-training consolidation “window” that is sufficient for the observed Fabp-mediated memory enhancement. Since Fabp overexpression increases consolidated daytime sleep bouts, these data support a role for longer naps in improving memory and provide a novel role for lipid-binding proteins in regulating memory consolidation concurrently with changes in behavioral state. PMID:21298037

  8. 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

  9. 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.

  10. 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

  11. 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

  12. Posttraumatic stress, depression and anxiety among adult long-term survivors of cancer in adolescence.

    PubMed

    Seitz, Diana C M; Besier, Tanja; Debatin, Klaus-Michael; Grabow, Desiree; Dieluweit, Ute; Hinz, Andreas; Kaatsch, Peter; Goldbeck, Lutz

    2010-06-01

    To determine the prevalence of posttraumatic stress, depression and anxiety in adults who have survived cancer (5 years) diagnosed in adolescence, as compared to healthy controls. Survivors (n=820) of cancer during adolescence (age M=30.4+/-6.0 years; M=13.7+/-6.0 years since diagnosis) and 1027 matched controls without history of cancer (age M=31.5+/-6.9 years) completed standardised questionnaires measuring posttraumatic stress, depression and anxiety. Additionally, sub-groups of 202 survivors and 140 controls with elevated scores received structured interviews to ascertain DSM-IV-diagnoses. A total of 22.4% of the survivors reported clinically relevant symptoms of posttraumatic stress, anxiety and/or depression compared to 14.0% of the controls (odds ratios [ORs] 1.77; 95% confidence interval [CI] 1.39-2.26). The odds of posttraumatic stress symptoms in male (OR 3.92, 95% CI 1.80-8.51) and female (OR 3.83, 95% CI 2.54-5.76) survivors were more than three times those in the controls. However, only female survivors reported symptoms of depression and anxiety significantly more often (respectively: OR 2.12, 95% CI 1.16-3.85; and OR 1.86, 95% CI 1.33-2.59) than the controls. A relevant subgroup of 24.3% of the survivors met DSM-IV criteria for at least one mental disorder compared to 15.3% of the controls. Survivors of cancer during adolescence show an elevated risk of presenting symptoms of posttraumatic stress, anxiety and/or depression during adulthood which is also reflected in a greater number of DSM-IV diagnoses when compared to controls. Comprehensive follow-up assessments should include the examination of possible psychological late effects of a cancer diagnosis in adolescence in order to identify survivors needing psychosocial interventions even years after the completion of successful medical treatment. Copyright 2010 Elsevier Ltd. All rights reserved.

  13. 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.

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

    PubMed

    Park, Albert; Conway, Mike

    2017-03-20

    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.

  15. 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

  16. Postsynaptic protein synthesis is required for presynaptic enhancement in persistent forms of long-term potentiation

    PubMed Central

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

    2013-01-01

    Long-term potentiation (LTP) in the hippocampus is a fundamental process underlying learning and memory in the brain. At CA3-CA1 synapses, three discrete forms of LTP (LTP1, 2, and 3) have been differentiated on the basis of their persistence, maintenance mechanisms, Ca2+ signaling pathways, expression loci, and electrophysiological requirements. We previously showed that LTP2 and LTP3 involve a presynaptic expression component that is established in a translation-dependent manner. Here we investigate the locus of translation required for presynaptic expression. Neurotransmitter release rate was estimated via FM 1-43 destaining from CA3 terminals in hippocampal slices from male Wistar rats (6–8 weeks). Destaining was measured at sites making putative contact with CA1 dendritic processes in stratum radiatum that had been filled with a membrane impermeable translation inhibitor and a fluorescent indicator. Our results suggest that inhibition of postsynaptic translation eliminates the enhanced release ordinarily observed at 160 min post-LTP induction, and that this effect is limited to sites closely apposed to the filled postsynaptic cell. We conclude that postsynaptic translation is required for the presynaptic component of LTP2 and LTP3 expression. These data considerably strengthen the mechanistic separation of LTP1, 2, and 3 and provide evidence for an expanded repertoire of communication between synaptic elements. PMID:23450328

  17. 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'.

  18. Activation of Synaptic Group II Metabotropic Glutamate Receptors Induces Long-Term Depression at GABAergic Synapses in CNS Neurons

    PubMed Central

    Tang, Zheng-Quan; Liu, Yu-Wei; Shi, Wei; Dinh, Emilie Hoang; Hamlet, William R.; Curry, Rebecca J.

    2013-01-01

    Metabotropic glutamate receptor (mGluR)-dependent homosynaptic long-term depression (LTD) has been studied extensively at glutamatergic synapses in the CNS. However, much less is known about heterosynaptic long-term plasticity induced by mGluRs at inhibitory synapses. Here we report that pharmacological or synaptic activation of group II mGluRs (mGluR II) induces LTD at GABAergic synapses without affecting the excitatory glutamatergic transmission in neurons of the chicken cochlear nucleus. Coefficient of variation and failure rate analysis suggested that the LTD was expressed presynaptically. The LTD requires presynaptic spike activity, but does not require the activation of NMDA receptors. The classic cAMP-dependent protein kinase A signaling is involved in the transduction pathway. Remarkably, blocking mGluR II increased spontaneous GABA release, indicating the presence of tonic activation of mGluR II by ambient glutamate. Furthermore, synaptically released glutamate induced by electrical stimulations that concurrently activated both the glutamatergic and GABAergic pathways resulted in significant and constant suppression of GABA release at various stimulus frequencies (3.3, 100, and 300 Hz). Strikingly, low-frequency stimulation (1 Hz, 15 min) of the glutamatergic synapses induced heterosynaptic LTD of GABAergic transmission, and the LTD was blocked by mGluR II antagonist, indicating that synaptic activation of mGluR II induced the LTD. This novel form of long-term plasticity in the avian auditory brainstem may play a role in the development as well as in temporal processing in the sound localization circuit. PMID:24089501

  19. 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

  20. Long-term enhancement of maze learning in mice via a generalized Mozart effect.

    PubMed

    Aoun, Peter; Jones, Timothy; Shaw, Gordon L; Bodner, Mark

    2005-12-01

    An animal model of the 'generalized Mozart effect' (GME) - enhanced/normalized higher brain function in response to music exposure - has been established. We extend those results in two studies using another species (mice). Study 1: (1) maze testing after music exposure was extended to a minimum of 6 hours; (2) no exposure to music in utero. Study 2: (1) music exposure time further reduced; (2) maze testing extended to 24 hours. Study 1: two mouse groups were exposed to music continuously for 10 hours per day for 10 weeks (Group I: Mozart's Sonata K.448, Group II: Beethoven's Fur Elise). After 10 weeks, the ability to negotiate a T-maze was assessed (recording working time in maze, number of errors). Maze ability was tested 6 hours following the last music exposure. Study 2: two mouse groups were exposed periodically to music (58% silence) 10 hours per day for 10 weeks. Experiments after 10 weeks examined the groups' abilities to run the maze (recording working time/errors). Experiments were conducted 24 hours following the last music exposure. The Mozart group exhibited significant enhancements compared with the control mice in both studies, i.e. significantly lower working time (p<0.05) and committed fewer errors. Observation of GME in another species supports its generality for the mammalian cortex. The absence of a GME in fMRI studies for the control music also indicates a neurophysiological basis. With extended exposure, GME is a long-term effect, indicating potential clinical importance. It has been demonstrated that GME reduces neuropathological spiking significantly in epileptics. We discuss the relevance of this study for epilepsy treatment.

  1. 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.

  2. 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

  3. 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.

  4. 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.

  5. Intrinsic and synaptic long-term depression of NTS relay of nociceptin- and capsaicin-sensitive cardiopulmonary afferents hyperactivity.

    PubMed

    Bantikyan, Armenak; Song, Gang; Feinberg-Zadek, Paula; Poon, Chi-Sang

    2009-03-01

    The nucleus tractus solitarius (NTS) in the caudal medulla is a gateway for a variety of cardiopulmonary afferents important for homeostatic regulation and defense against airway and cardiovascular insults and is a key central target potentially mediating the response habituation to these inputs. Here, whole-cell and field population action potential recordings and infrared imaging in rat brainstem slices in vitro revealed a compartmental pain-pathway-like organization of capsaicin-facilitated vs. nocistatin-facilitated/nociceptin-suppressed neuronal clusters in an NTS region, which receives cardiopulmonary A- and C-fiber afferents with differing capsaicin sensitivities. All capsaicin-sensitive neurons and a fraction of nociceptin-sensitive neurons expressed N-methyl-D: -aspartate (NMDA) receptor-dependent synaptic long-term depression (LTD) following afferent stimulation. All neurons also expressed activity-dependent decrease of excitability (intrinsic LTD), which converted to NMDA receptor-dependent intrinsic long-term potentiation after GABA(A) receptor blockade. Thus, distinct intrinsic and synaptic LTD mechanisms in the NTS specific to the relay of A- or C-fiber afferents may underlie the response habituation to persistent afferents hyperactivity that are associated with varying physiologic challenges and cardiopulmonary derangements-including hypertension, chronic cough, asthmatic bronchoconstriction, sustained elevated lung volume in chronic obstructive pulmonary disease or in continuous positive-airway-pressure therapy for sleep apnea, metabolic acidosis, and prolonged exposure to hypoxia at high altitude.

  6. Properties of the corticostriatal long term depression induced by medial prefrontal cortex high frequency stimulation in vivo.

    PubMed

    Braz, Barbara Y; Belforte, Juan E; Murer, M Gustavo; Galiñanes, Gregorio L

    2017-07-15

    Repetitive stimulation of cognitive forebrain circuits at frequencies capable of inducing corticostriatal long term plasticity is increasingly being used with therapeutic purposes in patients with neuropsychiatric disorders. However, corticostriatal plasticity is rarely studied in the intact brain. Our aim was to study the mechanisms of corticostriatal long term depression (LTD) induced by high frequency stimulation (HFS) of the medial prefrontal cortex in vivo. Our main finding is that the LTD induced in the dorsomedial striatum by medial prefrontal cortex HFS in vivo (prefrontostriatal LTD) is not affected by manipulations that block or reduce the LTD induced in the dorsolateral striatum by motor cortex HFS in brain slices, including pharmacological dopamine receptor and CB1 receptor blockade, chronic nigrostriatal dopamine depletion, CB1 receptor genetic deletion and selective striatal cholinergic interneuron (SCIN) ablation. Conversely, like in the hippocampus and other brain areas, prefrontostriatal LTD is NMDA receptor dependent. Thus, we describe a novel form of corticostriatal LTD that operates in brain circuits involved in reward and cognition and could be relevant for understanding the therapeutic effects of deep brain stimulation. Copyright © 2017 Elsevier Ltd. All rights reserved.

  7. 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.

  8. 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

  9. 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.

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

    PubMed Central

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

    2014-01-01

    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. PMID:25122682

  11. 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

  12. Long-term outcomes from the PEARLS randomized trial for the treatment of depression in patients with epilepsy.

    PubMed

    Chaytor, Naomi; Ciechanowski, Paul; Miller, John W; Fraser, Robert; Russo, Joan; Unutzer, Jurgen; Gilliam, Frank

    2011-03-01

    Depression is associated with higher rates of suicide and lower quality of life in individuals with epilepsy. We previously published the 12-month outcome from our randomized clinical trial of PEARLS (Ciechanowski P, Chaytor N, Miller J, et al. Epilepsy Behav. Epub 5 July 2010). The purpose of this study was to determine the long-term effectiveness of PEARLS, a home-based collaborative care intervention consisting of problem-solving treatment, behavioral activation, and psychiatric consultation, in individuals with epilepsy. Patients were randomly assigned to PEARLS (N=40) or usual care (N=40), and assessed at baseline and 6, 12, and 18 months. Patients assigned to PEARLS achieved lower depression severity (P<0.05) (Hopkins Symptoms Checklist-20), lower suicidal ideation (P<0.02), and better emotional well being (QOLIE-31) (P<0.02) over 18 months, compared with patients given the usual care. The PEARLS program significantly reduces depressive symptoms in adults with epilepsy, and this effect is maintained for 18 months after baseline and for more than 1 year after completion of home visits. Copyright © 2011 Elsevier Inc. All rights reserved.

  13. Diagnostic interview study of the prevalence of depression among public employees engaged in long-term relief work in Fukushima.

    PubMed

    Maeda, Masaharu; Ueda, Yukiko; Nagai, Masato; Fujii, Senta; Oe, Misari

    2016-09-01

    The Great East Japan Earthquake and in particular, the Fukushima Daiichi Nuclear Power Plant accident, have had a serious psychological impact on not only residents, but also relief workers in Fukushima. Although public employees work in highly stressful situations and play a very important role in long-term relief, their psychiatric features have yet to be clarified. The two aims of this study were to identify the current prevalence rate of depression and post-traumatic stress disorder among public employees working in the disaster area using diagnostic interviews, and to speculate on the psychosocial factors affecting their mental condition. We conducted diagnostic interviews and self-administered questionnaires with 168 public employees working in two coastal towns in Fukushima. Results showed that the current prevalence of depression among public employees is as high as 17.9%, in contrast to the relatively low prevalence of post-traumatic stress disorder (4.8%). Based on the results of self-administered questionnaires and interview contents, frequent exposure to strong complaints or anger from residents and role conflicts were considered the cause of the high prevalence of depression. The present study reveals the serious mental status of public employees working in Fukushima and sheds light on the urgent need to establish an efficient care network to provide adequate psychiatric intervention. © 2016 The Authors. Psychiatry and Clinical Neurosciences © 2016 Japanese Society of Psychiatry and Neurology.

  14. Decreased frequency but not amplitude of quantal synaptic responses associated with expression of corticostriatal long-term depression.

    PubMed

    Choi, S; Lovinger, D M

    1997-11-01

    We have investigated the site of expression of striatal long-term synaptic depression (LTD) using analysis of Sr2+-induced asynchronous release of quanta from stimulated synapses. The cumulative amplitude distribution of Sr2+-induced asynchronous synaptic responses overlaps with that of miniature EPSCs (mEPSCs), suggesting that Sr2+-induced asynchronous responses are quantal. Quantal amplitude at stimulated synapses is not significantly altered after LTD induction, whereas quantal frequency decreases after LTD induction. The decrease in quantal frequency is prevented when LTD expression is blocked by dialyzing 10 mM EGTA into the postsynaptic neuron. Our findings are most consistent with the idea that expression of striatal LTD involves decreased neurotransmitter release with no change in quantal amplitude, despite the fact that induction of striatal LTD involves postsynaptic mechanisms.

  15. 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.

  16. Deficient cerebellar long-term depression and impaired motor learning in mGluR1 mutant mice.

    PubMed

    Aiba, A; Kano, M; Chen, C; Stanton, M E; Fox, G D; Herrup, K; Zwingman, T A; Tonegawa, S

    1994-10-21

    mGluR1 mutant mice are viable but show characteristic cerebellar symptoms such as ataxic gait and intention tremor. The anatomy of the cerebellum is not overtly disturbed. Excitatory synaptic transmission from parallel fibers (PFs) to Purkinje cells and that from climbing fibers (CFs) to Purkinje cells appear to be functional, and voltage-gated Ca2+ channels of Purkinje cells are normal. Both PF and CF synapses display normal short-term synaptic plasticity to paired stimuli. By marked contrast, long-term depression (LTD) is clearly deficient and conditioned eyeblink response is impaired. We conclude that mGluR1 is required for the induction of LTD and that the ataxic behavior and impaired eyeblink conditioning of the mGluR1 mutant mice are primarily due to deficient LTD.

  17. 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.

  18. 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.'

  19. 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.

  20. Mirtazapine versus amitriptyline in the long-term treatment of depression: a double-blind placebo-controlled study.

    PubMed

    Montgomery, S A; Reimitz, P E; Zivkov, M

    1998-03-01

    Of 580 patients randomly assigned to short-term, double-blind treatment with either mirtazapine, amitriptyline or placebo, a total of 217 patients clinically judged to be responders subsequently continued on the same medication for up to 2 years in the long-term treatment study (mirtazapine, n = 74; amitriptyline, n = 86 and placebo, n = 57). The efficacy of mirtazapine in relapse prevention was seen in an analysis of the first 20 weeks data. Significantly fewer patients relapsed during treatment with mirtazapine compared with placebo (p < 0.05), and a significantly longer time to relapse was shown on the survival analysis. There was a significant advantage for amitriptyline compared with placebo in the first 20 weeks, with fewer patients relapsing. There was a significant advantage for mirtazapine compared with amitriptyline at 20 weeks seen on the survival analysis (p < 0.05). The significant advantage for mirtazapine compared with placebo was also seen in the prophylactic phase of treatment after 20 weeks. At the endpoint there were significantly more patients in the placebo group with a return of symptoms and significantly fewer showing sustained response. Amitriptyline was better than placebo with fewer patients suffering a recurrence of symptoms, but there was no difference from placebo in the proportion of patients with sustained response. Mirtazapine was well tolerated with a side-effect profile similar to that of placebo. The only adverse event reported significantly more frequently on mirtazapine than on placebo was weight gain. Objectively measured weight gain was more frequent with amitriptyline (22% of patients) compared with mirtazapine (13% of patients). Amitriptyline was associated with significantly more adverse events than either mirtazapine or placebo, in particular sedative and anticholinergic side effects. The efficacy of mirtazapine in reducing the risk of relapse and the recurrence of depression, which on some measures showed an advantage

  1. Canonical JAK-STAT signaling is pivotal for long-term depression at adult hippocampal temporoammonic-CA1 synapses.

    PubMed

    McGregor, Gemma; Irving, Andrew J; Harvey, Jenni

    2017-08-01

    The Janus kinase (JAK)-signal transducer and activator of transcription (STAT) signaling pathway is involved in numerous cellular processes and it is implicated in neurodegenerative disorders, like Alzheimer disease. Recent studies identified a crucial role for this pathway in activity-dependent long-term depression (LTD) at hippocampal Schaffer collateral (SC)-CA1 synapses. However, it is unclear whether JAK-STAT signaling also regulates excitatory synaptic function at the anatomically distinct temporoammonic (TA) input to CA1 neurons. Here we demonstrate that LTD at adult TA-CA1 synapses involves JAK-STAT signaling, but unlike SC-CA1 synapses, requires rapid gene transcription. TA-CA1 LTD requires NMDA receptor activation and is independent of PI3K or ERK signaling. JAK-STAT signaling was critical for TA-CA1 LTD as inhibition of JAK or STAT blocked LTD induction and prevented NMDA-induced AMPA (α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid) receptor internalization in hippocampal neurons. Moreover, an increase in phosphorylated JAK2 and STAT3 accompanied chemical induction of LTD and AMPA receptor internalization. STAT3-driven gene transcription was required for LTD as inhibition of STAT3-DNA binding, nuclear export, and gene transcription all prevented LTD induction. These data indicate an essential role for canonical JAK-STAT signaling in activity-dependent LTD at TA-CA1 synapses and provide valuable insight into the role of the TA input in hippocampal synaptic plasticity.-McGregor, G., Irving, A. J., Harvey, J. Canonical JAK-STAT signaling is pivotal for long-term depression at adult hippocampal temporoammonic-CA1 synapses. © FASEB.

  2. Prostaglandin E2 enhances long-term repopulation but does not permanently alter inherent stem cell competitiveness.

    PubMed

    Hoggatt, Jonathan; Mohammad, Khalid S; Singh, Pratibha; Pelus, Louis M

    2013-10-24

    Hematopoietic stem cell (HSC) transplantation is a lifesaving therapy for malignant and nonmalignant hematologic diseases and metabolic disorders. Although successful, hematopoietic transplantation can be hindered by inadequate stem cell number or poor engrafting efficiency. To overcome these deficits, we and others have previously reported the HSC-enhancing ability of a short-term exposure of prostaglandin E2 (PGE2); this strategy has now progressed to phase 1 clinical trials in double cord blood transplantation. To further analyze the short- and long-term effects of HSC exposure to PGE2, we followed the repopulation kinetics of PGE2-treated hematopoietic grafts through 5 serial transplantations and compared inherent long-term competitiveness in a HSC head-to-head secondary transplantation model. Treatment with PGE2 did not result in a long-term increase in HSC competitiveness, lineage bias, or enhanced proliferative potential, demonstrating that pulse exposure to PGE2 results in transient increases in HSC homing and engraftment potential.

  3. A novel bisindolylmaleimide derivative enhances functional recovery of heart after long-term hypothermic heart preservation.

    PubMed

    Katare, Rajesh Gopalrao; Zhitian, Zou; Sodeoka, Mikiko; Sasaguri, Shiro

    2007-06-27

    Functional recovery following heart transplantation mainly depends on the ability of preservative solution in providing the physical and biochemical environment so as to maintain the viability of the tissue during preservation and in reperfusion. Here we demonstrate the protective effects of a novel bisindolylmaleimide derivative, MS1, on enhancing the functional recovery of the heart following long-term hypothermic preservation when added to the preservative solution. After anesthesia and artificial ventilation, the hearts were rapidly isolated and perfused with Kreb's Henseleit buffer at 37 degrees C in working mode. After 30 minutes of perfusion, the hearts were arrested with cardioplegic solution and preserved in University of Wisconsin solution with (UW-MS1 group) or without MS1 (UW-Vehicle group) for 12 h at 4 degrees C. After 12 hours, the hearts were reperfused for 60 minutes. MS1 treated hearts showed: a) significant recovery of cardiac functions (P<0.001), b) well-preserved myocardial ATP levels (P<0.001), c) less myocardial water content (P<0.01), d) reduced oxidative stress (P<0.001), e) less intracellular swelling and well-preserved mitochondria, and g) activation of cell survival cascades compared to the control hearts preserved in UW solution without MS1. In contrast, these protective effects of MS1 were abolished on opening the permeability transition pore before MS1 treatment. These results altogether indicate the efficacy of this compound in protecting the myocardium against reperfusion injury and thus making this drug a clinically useful tool in patients undergoing reperfusion after cardiac surgeries.

  4. Studying frequency processing of the brain to enhance long-term memory and develop a human brain protocol.

    PubMed

    Friedrich, Wernher; Du, Shengzhi; Balt, Karlien

    2015-01-01

    The temporal lobe in conjunction with the hippocampus is responsible for memory processing. The gamma wave is involved with this process. To develop a human brain protocol, a better understanding of the relationship between gamma and long-term memory is vital. A more comprehensive understanding of the human brain and specific analogue waves it uses will support the development of a human brain protocol. Fifty-eight participants aged between 6 and 60 years participated in long-term memory experiments. It is envisaged that the brain could be stimulated through binaural beats (sound frequency) at 40 Hz (gamma) to enhance long-term memory capacity. EEG recordings have been transformed to sound and then to an information standard, namely ASCII. Statistical analysis showed a proportional relationship between long-term memory and gamma activity. Results from EEG recordings indicate a pattern. The pattern was obtained through the de-codification of an EEG recording to sound and then to ASCII. Stimulation of gamma should enhance long term memory capacity. More research is required to unlock the human brains' protocol key. This key will enable the processing of information directly to and from human memory via gamma, the hippocampus and the temporal lobe.

  5. Long term effects of childhood trauma on cortisol stress reactivity in adulthood and relationship to the occurrence of depression.

    PubMed

    Suzuki, Akiko; Poon, Lucia; Papadopoulos, Andrew S; Kumari, Veena; Cleare, Anthony J

    2014-12-01

    depression. On the other hand, patients who experience depression without a history of childhood trauma show enhanced cortisol stress reactivity, which could help explain the aetiology of their depressive illnesses. Differences between the current findings and those using other pharmacological and stress challenge paradigms may relate to the type of stimuli used and to dysfunction at different levels of the hypothalamic-pituitary-adrenal (HPA) axis. Copyright © 2014 Elsevier Ltd. All rights reserved.

  6. Combining pharmacotherapy and psychotherapy or monotherapy for major depression? A meta-analysis on the long-term effects.

    PubMed

    Karyotaki, E; Smit, Y; Holdt Henningsen, K; Huibers, M J H; Robays, J; de Beurs, D; Cuijpers, P

    2016-04-01

    The present meta-analysis aimed to examine to what extent combined pharmacotherapy with psychotherapy results in a different response to treatment compared to psychotherapy or pharmacotherapy alone in adults with major depression at six months or longer postrandomization. A systematic literature search resulted in 23 randomized controlled trials with 2184 participants. Combined treatment was compared to either psychotherapy or anti-depressant medication alone in both the acute phase and the maintenance phase. Odds ratios of a positive outcome were calculated for all comparisons. In acute phase treatment, combined psychotherapy with antidepressants outperformed antidepressants alone at six months or longer postrandomization in patients with major depressive disorder (OR=2.93, 95%CI 2.15-3.99, p<0.001). Heterogeneity was zero (95%CI 0-57%, p>0.05). However, combined therapy resulted in equal response to treatment compared to psychotherapy alone at six months or longer postrandomization. As for the maintenance treatment, combined maintenance psychotherapy with antidepressants resulted in better-sustained treatment response compared to antidepressants at six months or longer postrandomization (OR=1.61, 95%CI 1.14-2.27, p<0.05). Heterogeneity was zero (95%CI 0-68%, p>0.05). Combined therapy results in a superior enduring effect compared to antidepressants alone in patients with major depression. Psychotherapy is an adequate alternative for combined treatment in the acute phase as it is as effective as combined treatment in the long-term. Copyright © 2016 Elsevier B.V. All rights reserved.

  7. 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

  8. Dimorphic changes of some features of loving relationships during long-term use of antidepressants in depressed outpatients.

    PubMed

    Marazziti, Donatella; Akiskal, Hagop S; Udo, Mieko; Picchetti, Michela; Baroni, Stefano; Massimetti, Gabriele; Albanese, Francesco; Dell'Osso, Liliana

    2014-09-01

    The present study aimed at investigating the possible changes of some features of loving relationships during long-term treatment of depression with both selective serotonin reuptake inhibitors (SSRIs) and tricyclics (TCAs), by means of a specifically designed test, the so-called "Sex, Attachment, Love" (SALT) questionnaire. The sample was composed by 192 outpatients (123 women and 69 men, mean age±SD: 41.2±10.2 years), suffering from mild or moderate depression, according to DSM-IV-TR criteria, that were selected if they were treated with one antidepressant only for at least six months and were involved in a loving relationship. The results showed that SSRIs had a significant impact on the feelings of love and attachment towards the partner especially in men, while women taking TCAs complained of more sexual side effects than men. These data were supported also by the detection of a significant interaction between drug and sex on the "Love" and "Sex" domains. The present findings, while demonstrating a dimorphic effect of antidepressants on some component of loving relationships, need to be deepened in future studies. Copyright © 2014 Elsevier B.V. All rights reserved.

  9. Social Pavlovian conditioning: Short- and long-term effects and the role of anxiety and depressive symptoms

    PubMed Central

    Wilhelm, Frank H.; Boger, Sabrina; Georgii, Claudio; Klimesch, Wolfgang; Blechert, Jens

    2017-01-01

    Abstract Today’s stressors largely arise from social interactions rather than from physical threat. However, the dominant laboratory model of emotional learning relies on physical stimuli (e.g. electric shock) whereas adequate models of social conditioning are missing, possibly due to more subtle and multilayered biobehavioral responses to such stimuli. To fill this gap, we acquired a broad set of measures during conditioning to negative social unconditioned stimuli, also taking into account long-term maintenance of conditioning and inter-individual differences. Fifty-nine healthy participants underwent a classical conditioning task with videos of actors expressing disapproving (US-neg) or neutral (US-neu) statements. Static images of the corresponding actors with a neutral facial expression served as CS+ and CS−, predicting US-neg and US-neu, respectively. Autonomic and facial-muscular measures confirmed differential unconditioned responding whereas experiential CS ratings, event-related potentials, and evoked theta oscillations confirmed differential conditioned responding. Conditioning was maintained at 1 month and 1 year follow-ups on experiential ratings, especially in individuals with elevated anxiety and depressive symptoms, documenting the efficiency of social conditioning and its clinical relevance. This novel, ecologically improved conditioning paradigm uncovered a remarkably efficient multi-layered social learning mechanism that may represent a risk factor for anxiety and depression. PMID:27614767

  10. 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.

  11. 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…

  12. Behavioral Specifications of Reward-Associated Long-Term Memory Enhancement in Humans

    ERIC Educational Resources Information Center

    Wittmann, Bianca C.; Dolan, Raymond J.; Duzel, Emrah

    2011-01-01

    Recent functional imaging studies link reward-related activation of the midbrain substantia nigra-ventral tegmental area (SN/VTA), the site of origin of ascending dopaminergic projections, with improved long-term episodic memory. Here, we investigated in two behavioral experiments how (1) the contingency between item properties and reward, (2) the…

  13. 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…

  14. 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.

  15. 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.

  16. Long-Term Effects of a Screening Intervention for Depression on Suicide Rates among Japanese Community-Dwelling Older Adults.

    PubMed

    Oyama, Hirofumi; Sakashita, Tomoe

    2016-04-01

    To explore the long-term impact of a universal screening intervention for depression on suicide rates among older community-dwelling adults, with gender as an effect modifier. Controlled cohort study reporting long-term follow-up of previous research. Two sets of three municipalities in Japan were assigned as intervention and control regions and compared with the surrounding zone and prefecture. Intervention area residents aged 60 years and older (14,291) were invited to participate in a 2-year intervention (2005-2006). Four population-based dynamic cohorts of residents aged 65 years and older (1999-2010) were included as subjects, 6 years before and after the intervention started. At-risk residents within the intervention region (4,918) were invited for a two-step screening program; 2,552 participated in the program linked with care/support services for 2 years. An education program open to the public was held. Changes in suicide from a 6-year baseline to the 2-year intervention and a 4-year follow-up in the intervention region (11,700 adults ≥65 years) were compared with a matched control and two comparison areas using mixed-effects negative binomial regression models. Suicide rates among older adults exposed to screening were compared with those of the control region. Suicide rates in the intervention region decreased by 48%, which was significantly greater than in the three comparison areas. The program's benefits lasted longer for women than men. Screening exposure may be associated with decreased suicide risk over the 4-year follow-up. Universal screening may decrease suicide rates among older adults, with potential gender differences in treatment response. Copyright © 2016 American Association for Geriatric Psychiatry. Published by Elsevier Inc. All rights reserved.

  17. 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

  18. 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

  19. 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. Copyright © 2016 Elsevier Inc. All rights reserved.

  20. 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.

  1. 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.

  2. Long-term effects of adolescent smoking on depression and socioeconomic status in adulthood in an urban African American cohort.

    PubMed

    Strong, Carol; Juon, Hee-Soon; Ensminger, Margaret E

    2014-06-01

    Despite known adverse causal effects of cigarette smoking on mental health, findings for the effects of adolescent cigarette smoking on later depression and socioeconomic status remain inconclusive. Previous studies have had shorter follow-up periods and did not have a representative portion of the African American population. Using an analytical method that matches adolescent smokers with nonsmokers on childhood and background variables, this study aims to provide evidence on the effects of adolescent regular smoking on adult depression and socioeconomic status. Our longitudinal study is from the Woodlawn Study that followed 1,242 African Americans in Chicago from 1966-1967 (at age 6-7) through 2002-2003 (at age 42-43). We used a propensity score matching method to find a regular and a non-regular adolescent smoking group with similar childhood socioeconomic and family background and first grade academic and behavioral performance. We compared the matched samples to assess the longitudinal effects of adolescent smoking on adult outcomes. Comparing the matched 199 adolescent regular smokers and 199 non-regular smokers, we found statistical support for the effects of adolescent cigarette smoking on later educational attainment (OR, 2.13; 95 % CI, 1.34, 3.39) and long-term unemployment (OR, 1.74; 95 % CI, 1.11, 2.75), but did not find support for the effects on adulthood major depressive disorders. With a community population of urban African Americans followed for 40 years, our study contributes to the understanding of the relationships between adolescent smoking and later educational attainment and employment.

  3. 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

  4. To what extent do single symptoms from a depression rating scale predict risk of long-term sickness absence among employees who are free of clinical depression?

    PubMed

    Rugulies, Reiner; Hjarsbech, Pernille U; Aust, Birgit; Christensen, Karl Bang; Andersen, Rikke Voss; Borg, Vilhelm

    2013-10-01

    Depression rating scales have predicted long-term sickness absence (LTSA) in previous studies. With this study, we investigated to what extent single symptoms from a depression rating scale predicted LTSA among employees who were free of clinical depression. We studied 6,670 female employees in the Danish eldercare sector. Frequency of 12 depressive symptoms over the last 2 weeks was assessed with the Major Depression Inventory. A symptom was considered as elevated if it was present at least "slightly more than half of the time." Data were linked to a national register on LTSA (≥3 weeks). We calculated hazard ratios (HR) from Cox's proportional hazard models to analyze whether a symptom predicted time to onset of LTSA during a 1-year follow-up. Analyses were adjusted for age, family status, health behaviors, occupational group, and previous LTSA. Of the 12 symptoms, three predicted LTSA after adjustment for covariates: "felt low in spirits and sad" (HR = 1.41, 95 % CI = 1.05-1.89), "felt lacking in energy and strength" (HR = 1.33, 95 % CI = 1.08-1.64), and "had trouble sleeping at night" (HR = 1.38, 95 % CI = 1.09-1.74). Among female eldercare workers free of clinical depression, feelings of low spirits and sadness, feelings of lack of energy and strength, and sleep disturbances predict risk of LTSA. Interventions that decrease the prevalence of these symptoms might contribute to a reduction in LTSA in this population.

  5. Varenicline enhances dopamine release facilitation more than nicotine after long-term nicotine treatment and withdrawal.

    PubMed

    Perez, Xiomara A; Khroyan, Taline V; McIntosh, J Michael; Quik, Maryka

    2015-02-01

    An important factor contributing to the high relapse rates among smokers is nicotine withdrawal symptoms. Multiple studies suggest that decreased dopamine release in nucleus accumbens plays a key role in withdrawal. However, recent reports showed that long-term nicotine exposure itself also decreases accumbal dopamine release, suggesting that additional mechanisms are involved in withdrawal. Here, we used real-time cyclic voltammetry in brain slices containing the nucleus accumbens to further elucidate the changes in dopamine release linked to nicotine withdrawal. Rats received vehicle or nicotine via the drinking water for 2-3 months. Studies assessing the expression of somatic signs in vehicle-treated, nicotine-treated, and 24-h nicotine withdrawn rats showed that nicotine withdrawal led to a significant increase in somatic signs. Subsequent voltammetry studies showed that long-term nicotine decreased single-pulse-stimulated dopamine release via an interaction at α6β2* receptors. Nicotine withdrawal led to a partial recovery in α6β2* receptor-mediated release. In addition, long-term nicotine treatment alone increased dopamine release paired-pulse ratios and this was partially reversed with nicotine removal. We then evaluated the effect of bath-applied nicotine and varenicline on dopamine release. Nicotine and varenicline both decreased single-pulse-stimulated release in vehicle-treated, nicotine-treated, and nicotine withdrawn rats. However, bath-applied varenicline increased paired-pulse ratios to a greater extent than nicotine during long-term nicotine treatment and after its withdrawal. Altogether these data suggest that nicotine withdrawal is associated with a partial restoration of dopamine release measures to control levels and that varenicline's differential modulation of dopamine release may contribute to its mechanism of action.

  6. 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.

  7. 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

  8. 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

  9. 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.

  10. 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

  11. 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

  12. The association of perseverative negative thinking with depression, anxiety and emotional distress in people with long term conditions: A systematic review.

    PubMed

    Trick, Leanne; Watkins, Edward; Windeatt, Stacey; Dickens, Chris

    2016-12-01

    Depression is common in people with long term conditions, and is associated with worse medical outcomes. Previous research shows perseverative negative thinking (e.g. worry, rumination) predicts subsequent depression and worse medical outcomes, suggesting interventions targeting perseverative negative thinking could improve depression and medical outcomes. Previous studies recruited healthy individuals, however. This review aimed to determine the temporal relationship and strength of prospective association of perseverative negative thinking with depression, anxiety and emotional distress in people with long term conditions. Four electronic databases were searched for studies including standardised measures of perseverative negative thinking and depression, anxiety or emotional distress, and which presented prospective associations. Findings were narratively synthesized. Thirty studies were identified in a range of long term conditions. Perseverative negative thinking and subsequent depression, anxiety or emotional distress were significantly correlated in the majority of studies (bivariate r=0.23 to r=0.73). 25 studies controlled for confounders, and in 15 perseverative negative thinking predicted subsequent depression, anxiety or emotional distress. Results varied according to condition and study quality. Six of 7 studies found bivariate associations between depression, anxiety or emotional distress and subsequent perseverative negative thinking, though 2 studies controlling for key covariates found no association. Few studies assessed the impact of perseverative negative thinking on medical outcomes. Strongest evidence supported perseverative negative thinking predicting subsequent depression, anxiety and emotional distress in people with long term conditions. Further prospective research is warranted to clarify the association of perseverative negative thinking with subsequent poor medical outcomes. Copyright © 2016 Elsevier Inc. All rights reserved.

  13. rhEPO Enhances Cellular Anti-oxidant Capacity to Protect Long-Term Cultured Aging Primary Nerve Cells.

    PubMed

    Wang, Huqing; Fan, Jiaxin; Chen, Mengyi; Yao, Qingling; Gao, Zhen; Zhang, Guilian; Wu, Haiqin; Yu, Xiaorui

    2017-08-01

    Erythropoietin (EPO) may protect the nervous system of animals against aging damage, making it a potential anti-aging drug for the nervous system. However, experimental evidence from natural aging nerve cell models is lacking, and the efficacy of EPO and underlying mechanism of this effect warrant further study. Thus, the present study used long-term cultured primary nerve cells to successfully mimic the natural aging process of nerve cells. Starting on the 11th day of culture, cells were treated with different concentrations of recombinant human erythropoietin (rhEPO). Using double immunofluorescence labeling, we found that rhEPO significantly improved the morphology of long-term cultured primary nerve cells and increased the total number of long-term cultured primary cells. However, rhEPO did not improve the ratio of nerve cells. A 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay was used to measure nerve cell activity and showed that rhEPO significantly improved the activity of long-term cultured primary nerve cells. Moreover, Annexin V-fluorescein isothiocyanate (FITC)/propidium iodide (PI) double immunofluorescence labeling flow cytometry revealed that rhEPO reduced the apoptotic rate of long-term cultured primary nerve cells. Senescence-associated β-galactosidase (SA-β-gal) immunohistochemistry staining showed that rhEPO significantly reduced the aging rate of long-term cultured primary nerve cells. Immunochemistry revealed that rhEPO enhanced intracellular superoxide dismutase (SOD) activity and glutathione (GSH) abundance and reduced the intracellular malondialdehyde (MDA) level. In addition, this effect depended on the dose, was maximized at a dose of 100 U/ml and was more pronounced than that of vitamin E. In summary, this study finds that rhEPO protects long-term cultured primary nerve cells from aging in a dose-dependent manner. The mechanism of this effect may be associated with the enhancement of the intracellular anti

  14. 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.

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

    PubMed

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

    2015-08-01

    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.

  16. 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

  17. Naringin Enhances CaMKII Activity and Improves Long-Term Memory in a Mouse Model of Alzheimer's Disease.

    PubMed

    Wang, Dong-Mei; Yang, Ya-Jun; Zhang, Li; Zhang, Xu; Guan, Fei-Fei; Zhang, Lian-Feng

    2013-03-11

    The Amyloid-β (Aβ)-induced impairment of hippocampal synaptic plasticity is an underlying mechanism of memory loss in the early stages of Alzheimer's disease (AD) in human and mouse models. The inhibition of the calcium/calmodulin-dependent protein kinase II (CaMKII) autophosphorylation plays an important role in long-term memory. In this study, we isolated naringin from Pomelo peel (a Citrus species) and studied its effect on long-term memory in the APPswe/PS1dE9 transgenic mouse model of AD. Three-month-old APPswe/PS1dE9 transgenic mice were randomly assigned to a vehicle group, two naringin (either 50 or 100 mg/kg body weight/day) groups, or an Aricept (2 mg/kg body weight/day) group. After 16 weeks of treatment, we observed that treatment with naringin (100 mg/kg body weight/day) enhanced the autophosphorylation of CaMKII, increased the phosphorylation of the α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic (AMPA) receptor at a CaMKII-dependent site and improved long-term learning and memory ability. These findings suggest that the increase in CaMKII activity may be one of the mechanisms by which naringin improves long-term cognitive function in the APPswe/PS1dE9 transgenic mouse model of AD.

  18. Rapid and Delayed Effects of Pulsed Radiofrequency on Neuropathic Pain: Electrophysiological, Molecular, and Behavioral Evidence Supporting Long-Term Depression.

    PubMed

    Huang, Ren-Yu; Liao, Chia-Chi; Tsai, Shih-Ying; Yen, Chen-Tung; Lin, Chii-Wann; Chen, Tsung-Chi; Lin, Wei-Tso; Chang, Chi-Heng; Wen, Yeong-Ray

    2017-02-01

    Pulsed radiofrequency (PRF) has been widely employed for ameliorating clinical neuropathic pain. How PRF alters electrophysiological transmission and modulates biomolecular functions in neural tissues has yet to be clarified. We previously demonstrated that an early application of low-voltage bipolar PRF adjacent to the dorsal root ganglion (DRG) reduced acute neuropathic pain in animals. By contrast, the present study investigated how PRF alters postsynaptic sensitization to produce early and delayed effects on neuropathic pain. Our objective was to test the hypothesis that a 5-minute session of PRF could rapidly produce selective long-term depression (LTD) on C-fiber-mediated spinal sensitization and sustain the effect through the long-lasting inhibition of injury-induced ERK-MAPK activation. This may explain the prolonged analgesic effect of PRF on chronic neuropathic pain. Experiments were conducted on both normal rats and neuropathic pain rats that received spinal nerve ligation (SNL) 8 days prior. An animal laboratory in a medical center of a university in Taiwan. We first compared changes in field potentials in the L5 superficial spinal dorsal horn (SDH) that were evoked by conditioning electrical stimuli in the sciatic nerve in male adult rats before (as the baseline) and after PRF stimulation for at least 2 hours. Bipolar PRF was applied adjacent to the L5 DRG at an intensity of 5 V for 5 minutes, whereas the control rats were treated with sham applications. The electrophysiological findings were tested for any correlation with induction of spinal phospho-ERK (p-ERK) in normal and neuropathic pain rats. We then investigated the delayed effect of PRF on SNL-maintained pain behaviors for 2 weeks as well as p-ERK in SDH among the control, SNL, and PRF groups. Finally, potential injury in the DRGs after PRF stimulation was evaluated through behavioral observations and ATF-3, a neuronal stress marker. In the evoked field-potential study, the recordings mediated

  19. Enhancing long-term memory with stimulation tunes visual attention in one trial.

    PubMed

    Reinhart, Robert M G; Woodman, Geoffrey F

    2015-01-13

    Scientists have long proposed that memory representations control the mechanisms of attention that focus processing on the task-relevant objects in our visual field. Modern theories specifically propose that we rely on working memory to store the object representations that provide top-down control over attentional selection. Here, we show that the tuning of perceptual attention can be sharply accelerated after 20 min of noninvasive brain stimulation over medial-frontal cortex. Contrary to prevailing theories of attention, these improvements did not appear to be caused by changes in the nature of the working memory representations of the search targets. Instead, improvements in attentional tuning were accompanied by changes in an electrophysiological signal hypothesized to index long-term memory. We found that this pattern of effects was reliably observed when we stimulated medial-frontal cortex, but when we stimulated posterior parietal cortex, we found that stimulation directly affected the perceptual processing of the search array elements, not the memory representations providing top-down control. Our findings appear to challenge dominant theories of attention by demonstrating that changes in the storage of target representations in long-term memory may underlie rapid changes in the efficiency with which humans can find targets in arrays of objects.

  20. Enhanced, simplified glucose sensors: long-term clinical application of wearable artificial endocrine pancreas.

    PubMed

    Shichiri, M; Sakakida, M; Nishida, K; Shimoda, S

    1998-01-01

    At present, 2 major problems should be solved before long-term application of the wearable artificial endocrine pancreas, the development of a reliable and stable glucose monitoring system and the development of a subcutaneous insulin infusion algorithm. With either a miniaturized extracorporeal glucose monitoring system based on microdialysis sampling method or a ferrocene-mediated needle-type glucose sensor covered with highly biocompatible membrane, poly(2-methacryloyloxyethyl phosphorylcholine-co-n-butyl methacrylate) (poly[MPC-co-BMA]) membrane, subcutaneous glucose concentrations could be monitored for 7 days without any in vivo calibrations, followed by 14 days with one point calibration. Considering the management and safety of the insulin delivery route, subcutaneous insulin infusion is obligatory. With the subcutaneous insulin infusion algorithm using a short acting insulin analogue (Insulin Lispro), near physiological glycemic control could be established in diabetic patients without showing any delayed hyperinsulinemia or hypoglycemia. The wearable artificial endocrine pancreas is now recognized as an excellent therapeutic tool for regulating blood glucose excursions physiologically in ambulatory diabetic patients on a long-term basis.

  1. 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

  2. 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…

  3. 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…

  4. 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…

  5. 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.

  6. 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

  7. Genetic activation of ERK5 MAP kinase enhances adult neurogenesis and extends hippocampus-dependent long-term memory.

    PubMed

    Wang, Wenbin; Pan, Yung-Wei; Zou, Junhui; Li, Tan; Abel, Glen M; Palmiter, Richard D; Storm, Daniel R; Xia, Zhengui

    2014-02-05

    Recent studies have shown that inhibition of adult neurogenesis impairs the formation of hippocampus-dependent memory. However, it is not known whether increasing adult neurogenesis affects the persistence of hippocampus-dependent long-term memory. Furthermore, signaling mechanisms that regulate adult neurogenesis are not fully defined. We recently reported that the conditional and targeted knock-out of ERK5 MAP kinase in adult neurogenic regions of the mouse brain attenuates adult neurogenesis in the hippocampus and disrupts several forms of hippocampus-dependent memory. Here, we developed a gain-of-function knock-in mouse model to specifically activate endogenous ERK5 in the neurogenic regions of the adult brain. We report that the selective and targeted activation of ERK5 increases adult neurogenesis in the dentate gyrus by enhancing cell survival, neuronal differentiation, and dendritic complexity. Conditional ERK5 activation also improves the performance of challenging forms of spatial learning and memory and extends hippocampus-dependent long-term memory. We conclude that enhancing signal transduction of a single signaling pathway within adult neural stem/progenitor cells is sufficient to increase adult neurogenesis and improve the persistence of hippocampus-dependent memory. Furthermore, activation of ERK5 may provide a novel therapeutic target to improve long-term memory.

  8. Long-term treatment with a health product (Squina Diacylglyceryl Ether) enhances innate and adaptive immunity in mice.

    PubMed

    Leung, Hoi Yan; Ko, Kam Ming

    2012-11-26

    This study aimed to investigate the effects of a health product Squina (Diacylglyceryl Ether) (DAGE) on innate and adaptive immunity in mice. Both ex vivo/ in vivo mouse models and an in vitro system using cultured mouse splenocytes were recruited for the assessment of innate and adaptive immunity. For the innate immune response, DAGE extract treatment enhanced the LPS-induced IL1-β secretion by activated macrophages in vitro and long-term DAGE treatment (0.18 and 1.8 g/kg × 20 doses) elevated the phagocytic activity of macrophages, as well as natural killer cell activity in mice. The DAGE-induced increase in macrophage phagocytic and natural killer cell activities were accompanied by the suppression of tumor growth in Sarcoma-180 cell-inoculated mice. For the adaptive immune response, long-term DAGE treatment enhanced the splenocyte index and concanavalin A- stimulated proliferation ex vivo in mice. Consistently, the incubation with DAGE extract potentiated the concanavalin A-stimulated proliferation in mouse splenocytes in vitro. In conclusion, the results show that long-term DAGE treatment produces stimulatory effects on both innate and adaptive immunity in mice.

  9. 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

  10. 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.

  11. Roles of p75NTR, long-term depression and cholinergic transmission in anxiety and acute stress coping

    PubMed Central

    Martinowich, Keri; Schloesser, Robert J.; Lu, Yuan; Jimenez, Dennisse V.; Paredes, Daniel; Greene, Joshua S.; Greig, Nigel H.; Manji, Husseini K.; Lu, Bai

    2011-01-01

    Background Stress is causally associated with anxiety. While the underlying cellular mechanisms are not well understood, the basal forebrain cholinergic neurons (BFCNs) have been implicated in stress response. p75NTR is a pan-neurotrophin receptor expressed almost exclusively in BFCNs in adult brain. The present study investigates whether and how p75NTR, via regulation of the cholinergic system and hippocampal synaptic plasticity, influences stress-related behaviors. Methods We used a combination of slice electrophysiology, behavioral analyses, pharmacology, in vivo microdialysis and neuronal activity mapping to assess the role of p75NTR in mood and stress-related behaviors and its underlying cellular and molecular mechanisms. Results We show that acute stress enables hippocampal long-term depression (LTD) in adult wild-type mice, but not in mice lacking p75NTR. The p75NTR mutant mice also exhibit two distinct behavioral impairments: baseline anxiety-like behavior and a deficit in coping with and recovering from stressful situations. Blockade of stress-enabled LTD with a GluA2-derived peptide impaired stress recovery without affecting baseline anxiety. Pharmacological manipulations of cholinergic transmission mimicked the p75NTR perturbation in both baseline anxiety and responses to acute stress. Finally, we show evidence of misregulated cholinergic signaling in animals with p75NTR deletion. Conclusions Our results suggest that loss of p75NTR leads to changes in hippocampal cholinergic signaling, which may be involved in regulation of stress-enabled hippocampal LTD and in modulating behaviors related to stress and anxiety. PMID:21978521

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

    PubMed

    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.

  13. 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

  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. 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.

  16. 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

  17. 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

  18. 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.

  19. Vortioxetine (Lu AA21004) in the long-term open-label treatment of major depressive disorder.

    PubMed

    Baldwin, David S; Hansen, Thomas; Florea, Ioana

    2012-10-01

    The primary objective of this study was to evaluate the safety and tolerability of the investigational drug vortioxetine (Lu AA21004) in the long-term treatment of patients with major depressive disorder. Patients entered this 52-week, open-label extension study after completing an 8-week lead-in study. Safety and tolerability were evaluated at regular intervals on the basis of spontaneously reported adverse events (AEs), clinical safety laboratory tests, vital signs, ECG and physical examination. Effectiveness of treatment was assessed using the Montgomery-Åsberg Depression Rating Scale (MADRS) total score. A total of 535 patients were treated and 61.3% (n = 328) completed the study, resulting in 393 patient years of exposure to vortioxetine. AEs reported by ≥10% of patients were nausea, headache, and nasopharyngitis. Taken together, six patients had eight AEs related to sexual dysfunction. There were no clinically significant safety findings with respect to mean changes of vital signs, weight, ECG parameters, or clinical laboratory values. Patients entered the extension study with a mean MADRS total score of 13.5 ± 8.7. The mean MADRS total score decreased (improved) by approximately 8 points to 5.5 ± 6.0 at Week 52 (OC). By the end of the study, the proportion of responders had increased from 63% to 94% (OC), as had the proportion in remission (MADRS ≤10), increasing from 42% to 83% (OC). Patients in remission (n = 226) at the start of this study had a relapse rate (MADRS ≥22) of 9.7%. As with all open-label studies, the conclusions that can be drawn are limited by the lack of a placebo control, making it difficult to assess causality of any changes in outcome measures. However, on the basis of these findings, vortioxetine (2.5, 5, 10 mg/day) demonstrated a favourable safety and tolerability profile and maintained effectiveness over 12 months of treatment. This study has the ClinicalTrials.gov identifier: NCT00694304.

  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. 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.

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

    PubMed

    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.

  3. Light Enhances Survival of Dinoroseobacter shibae during Long-Term Starvation

    PubMed Central

    Soora, Maya; Cypionka, Heribert

    2013-01-01

    Aerobic anoxygenic phototrophs (AAPs) as being photoheterotrophs require organic substrates for growth and use light as a supplementary energy source under oxic conditions. We hypothesized that AAPs benefit from light particularly under carbon and electron donor limitation. The effect of light was determined in long-term starvation experiments with Dinoroseobacter shibae DFL 12T in both complex marine broth and defined minimal medium with succinate as the sole carbon source. The cells were starved over six months under three conditions: continuous darkness (DD), continuous light (LL), and light/dark cycle (LD, 12 h/12 h, 12 µmol photons m−2 s−1). LD starvation at low light intensity resulted in 10-fold higher total cell and viable counts, and higher bacteriochlorophyll a and polyhydroxyalkanoate contents. This coincided with better physiological fitness as determined by respiration rates, proton translocation and ATP concentrations. In contrast, LD starvation at high light intensity (>22 µmol photons m−2 s−1, LD conditions) resulted in decreasing cell survival rates but increasing carotenoid concentrations, indicating a photo-protective response. Cells grown in complex medium survived longer starvation (more than 20 weeks) than those grown in minimal medium. Our experiments show that D. shibae benefits from the light and dark cycle, particularly during starvation. PMID:24386315

  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. 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

  6. Super chilling enhances preservation of the freshness of salted egg yolk during long-term storage.

    PubMed

    Yanagisawa, T; Watanuki, C; Ariizumi, M; Shigematsu, Y; Kobayashi, H; Hasegawa, M; Watanabe, K

    2009-03-01

    Pasteurized egg yolk with 10% (w/w) salt was stored at 5, -5, -15, -20, and -30 degrees C for 1 to 6 mo, respectively. Changes in generation of volatiles of the stored samples (5 and -5 degrees C for 6 mo) were analyzed by SPME-GC-MS. Emulsifying properties of egg yolk stored at -5, -15, -20, and -30 degrees C for 1 mo, respectively, were also evaluated by measurement of emulsion particle diameters in model emulsions prepared with the yolk samples. In addition, structural changes in low-density lipoprotein (LDL) in the egg yolks dependent on storage conditions for 6 mo were evaluated by (31)P-NMR. Volatile compounds such as hexanal, 2-methylbutanal, and 3-methylbutanal increased in egg yolk during storage at 5 degrees C; however, volatile compounds hardly increased in any samples stored at -5 degrees C (super chilling). The mean emulsion particle diameter in super chilled egg yolk was significantly smaller than that in egg yolk stored at the other lower temperatures. In addition, the results of (31)P-NMR evaluation suggested that prevention of structural changes of LDL resulted in maintenance of emulsifying properties of egg yolk. Thus, these results indicate that super chilling is an effective means of preserving salted egg yolk during long-term storage.

  7. 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.

  8. Differences in symptoms, functioning, and quality of life between women on long-term sick-leave with musculoskeletal pain with and without concomitant depression.

    PubMed

    Jansen, Gunilla Brodda; Linder, Jürgen; Ekholm, Kristina Schüldt; Ekholm, Jan

    2011-01-01

    The aim was to describe the differences in symptoms, functioning and quality of life between women on long-term sick-leave due to protracted musculoskeletal pain with and without concomitant depression. Descriptive and comparisons with/without comorbid depression. 332 female patients were examined by three specialist physicians in psychiatry, orthopedic surgery, and rehabilitation medicine and assigned to four groups according to the ICD-10 diagnoses: low back/joint disorders (LBJ, n = 150), myalgia (M, n = 43), fibromyalgia (FM, n = 87), or depression without somatic pain diagnosis (DE, n = 52). Patients with somatic pain conditions LBJ, M, or FM showed more activity-related difficulties if concomitant depression was present during the activities 'focusing attention', 'making decisions', and 'undertaking a single task'; and in the domains 'energy level', 'memory functions', 'emotional functions', and 'optimism/pessimism'. Patients with FM and concomitant depression perceived higher pain intensity than patients in group DE. No statistically significant differences in physically related activities were noted between each of the somatic pain conditions with and without coexisting depression. FM patients with coexisting depression reported fewer painful sites on their pain drawings compared with FM-patients without depression. Patients with LBJ or FM and concomitant depression reported lower quality of life in the dimensions vitality, social functioning, emotional role, and mental health. Comorbid depression affected disability and restricted working capacity by reducing mental activity and functioning but not by affecting physical activity problems. Women on long-term sick-leave, who have concomitant depression with LBJ or FM, also have more difficulties in focusing attention, making decisions, and carrying out tasks, and with memory functions and optimism/pessimism, as well as reduced quality of life in the dimensions of vitality, social functioning, emotional role

  9. 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.

  10. 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.

  11. 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. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  12. 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.

  13. 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

  14. 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.

  15. 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

  16. 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

  17. Superior Long-Term Synaptic Memory Induced by Combining Dual Pharmacological Activation of PKA and ERK with an Enhanced Training Protocol

    ERIC Educational Resources Information Center

    Liu, Rong-Yu; Neveu, Curtis; Smolen, Paul; Cleary, Leonard J.; Byrne, John H.

    2017-01-01

    Developing treatment strategies to enhance memory is an important goal of neuroscience research. Activation of multiple biochemical signaling cascades, such as the protein kinase A (PKA) and extracellular signal-regulated kinase (ERK) pathways, is necessary to induce long-term synaptic facilitation (LTF), a correlate of long-term memory (LTM).…

  18. Phosphorylation of threonine-19 of PSD-95 by GSK-3β is required for PSD-95 mobilization and long-term depression.

    PubMed

    Nelson, Christopher D; Kim, Myung Jong; Hsin, Honor; Chen, Yelin; Sheng, Morgan

    2013-07-17

    Activity of glycogen synthase kinase-3β (GSK-3β) is required for long-term depression (LTD) via molecular mechanisms that are incompletely understood. Here, we report that PSD-95, a major scaffold protein of the postsynaptic density (PSD) that promotes synaptic strength, is phosphorylated on threonine-19 (T19) by GSK-3β. In cultured rat hippocampal neurons, phosphorylation of T19 increases rapidly with chemical LTD and is attenuated by pharmacologic or genetic suppression of GSK-3β. In organotypic rat hippocampal slices, we find that a nonphosphorylatable PSD-95 mutant (T19A) tagged with photoactivatable green fluorescent protein (PAGFP) shows enhanced stability in dendritic spines versus wild-type PSD-95, whereas the phosphomimetic mutant (PSD-95-T19D) is more readily dispersed. Further, overexpression of PSD-95-T19A, but not WT-PSD-95, impairs AMPA receptor internalization and the induction of LTD. These data indicate that phosphorylation on T19 by GSK-3β destabilizes PSD-95 within the PSD and is a critical step for AMPA receptor mobilization and LTD.

  19. Phosphorylation of Threonine-19 of PSD-95 by GSK-3β is Required for PSD-95 Mobilization and Long-Term Depression

    PubMed Central

    Nelson, Christopher D.; Kim, Myung Jong; Hsin, Honor; Chen, Yelin

    2013-01-01

    Activity of glycogen synthase kinase-3β (GSK-3β) is required for long-term depression (LTD) via molecular mechanisms that are incompletely understood. Here, we report that PSD-95, a major scaffold protein of the postsynaptic density (PSD) that promotes synaptic strength, is phosphorylated on threonine-19 (T19) by GSK-3β. In cultured rat hippocampal neurons, phosphorylation of T19 increases rapidly with chemical LTD and is attenuated by pharmacologic or genetic suppression of GSK-3β. In organotypic rat hippocampal slices, we find that a nonphosphorylatable PSD-95 mutant (T19A) tagged with photoactivatable green fluorescent protein (PAGFP) shows enhanced stability in dendritic spines versus wild-type PSD-95, whereas the phosphomimetic mutant (PSD-95-T19D) is more readily dispersed. Further, overexpression of PSD-95-T19A, but not WT-PSD-95, impairs AMPA receptor internalization and the induction of LTD. These data indicate that phosphorylation on T19 by GSK-3β destabilizes PSD-95 within the PSD and is a critical step for AMPA receptor mobilization and LTD. PMID:23864697

  20. CA1 Pyramidal Cell Theta-Burst Firing Triggers Endocannabinoid-Mediated Long-Term Depression at Both Somatic and Dendritic Inhibitory Synapses

    PubMed Central

    Younts, Thomas J.; Chevaleyre, Vivien

    2013-01-01

    Endocannabinoids (eCBs) are retrograde lipid messengers that, by targeting presynaptic type 1 cannabinoid receptors (CB1Rs), mediate short- and long-term synaptic depression of neurotransmitter release throughout the brain. Short-term depression is typically triggered by postsynaptic, depolarization-induced calcium rises, whereas long-term depression is induced by synaptic activation of Gq/11 protein-coupled receptors. Here we report that a physiologically relevant pattern of postsynaptic activity, in the form of theta-burst firing (TBF) of hippocampal CA1 pyramidal neurons, can trigger long-term depression of inhibitory transmission (iLTD) in rat hippocampal slices. Paired recordings between CA1 interneurons and pyramidal cells, followed by post hoc morphological reconstructions of the interneurons' axon, revealed that somatic and dendritic inhibitory synaptic inputs equally expressed TBF-induced iLTD. Simultaneous recordings from neighboring pyramidal cells demonstrated that eCB signaling triggered by TBF was highly restricted to only a single, active cell. Furthermore, pairing submaximal endogenous activation of metabotropic glutamate or muscarinic acetylcholine receptors with submaximal TBF unmasked associative iLTD. Although CB1Rs are also expressed at Schaffer-collateral excitatory terminals, long-term plasticity under various recording conditions was spared at these synapses. Consistent with this observation, TBF also shifted the balance of excitation and inhibition in favor of excitatory throughput, thereby altering information flow through the CA1 circuit. Given the near ubiquity of burst-firing activity patterns and CB1R expression in the brain, the properties described here may be a general means by which neurons fine tune the strength of their inputs in a cell-wide and cell-specific manner. PMID:23966696

  1. 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.

  2. 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.

  3. 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.

  4. 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.

  5. 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

  6. 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.

  7. 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

  8. 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

  9. The effects of test-enhanced learning on long-term retention in AAN annual meeting courses.

    PubMed

    Larsen, Douglas P; Butler, Andrew C; Aung, Wint Y; Corboy, John R; Friedman, Deborah I; Sperling, Michael R

    2015-02-17

    We measured the long-term retention of knowledge gained through selected American Academy of Neurology annual meeting courses and compared the effects of repeated quizzing (known as test-enhanced learning) and repeated studying on that retention. Participants were recruited from 4 annual meeting courses. All participants took a pretest. This randomized, controlled trial utilized a within-subjects design in which each participant experienced 3 different postcourse activities with each activity performed on different material. Each key information point from the course was randomized in a counterbalanced fashion among participants to one of the 3 activities: repeated short-answer quizzing, repeated studying, and no further exposure to the materials. A final test covering all information points from the course was taken 5.5 months after the course. Thirty-five participants across the 4 courses completed the study. Average score on the pretest was 36%. Performance on the final test showed that repeated quizzing led to significantly greater long-term retention relative to both repeated studying (55% vs 46%; t[34] = 3.28, SEM = 0.03, p = 0.01, d = 0.49) and no further exposure (55% vs 44%; t[34] = 3.16, SEM = 0.03, p = 0.01, d = 0.58). Relative to the pretest baseline, repeated quizzing helped participants to retain almost twice as much of the knowledge acquired from the course compared to repeated studying or no further exposure. Whereas annual meeting continuing medical education (CME) courses lead to long-term gains in knowledge, when repeated quizzing is added, retention is significantly increased. CME planners may consider adding repeated quizzing to increase the impact of their courses. © 2015 American Academy of Neurology.

  10. Downregulation of renal sodium transporters and tonicity-responsive enhancer binding protein by long-term treatment with cyclosporin A.

    PubMed

    Lim, Sun Woo; Ahn, Kyung Ohk; Sheen, Mee Rie; Jeon, Un Sil; Kim, Jin; Yang, Chul Woo; Kwon, H Moo

    2007-02-01

    Tonicity-responsive enhancer binding protein (TonEBP) is a transcriptional activator that is regulated by ambient tonicity. TonEBP protects the renal medulla from the deleterious effects of hyperosmolality and regulates the urinary concentration by stimulating aquaporin-2 and urea transporters. The therapeutic use of cyclosporin A (CsA) is limited by nephrotoxicity that is manifested by reduced GFR, fibrosis, and tubular defects, including reduced urinary concentration. It was reported recently that long-term CsA treatment was associated with decreased renal expression of TonEBP target genes, including aquaporin-2, urea transporter, and aldose reductase. This study tested the hypothesis that long-term CsA treatment reduces the salinity/tonicity of the renal medullary interstitium as a result of inhibition of active sodium transporters, leading to downregulation of TonEBP. CsA treatment for 7 d did not affect TonEBP or renal function. Whereas expression of sodium transporters was altered, the medullary tonicity seemed unchanged. Conversely, 28 d of CsA treatment led to downregulation of TonEBP and overt nephrotoxicity. The downregulation of TonEBP involved reduced expression, cytoplasmic shift, and reduced transcription of its target genes. This was associated with reduced expression of active sodium transporters-sodium/potassium/chloride transporter type 2 (NKCC2), sodium/chloride transporter, and Na(+),K(+)-ATPase-along with increased sodium excretion and reduced urinary concentration. Infusion of vasopressin restored the expression of NKCC2 in the outer medulla as well as the expression and the activity of TonEBP. It is concluded that the downregulation of TonEBP in the setting of long-term CsA administration is secondary to the reduced tonicity of the renal medullary interstitium.

  11. The effects of test-enhanced learning on long-term retention in AAN annual meeting courses

    PubMed Central

    Butler, Andrew C.; Aung, Wint Y.; Corboy, John R.; Friedman, Deborah I.; Sperling, Michael R.

    2015-01-01

    Objective: We measured the long-term retention of knowledge gained through selected American Academy of Neurology annual meeting courses and compared the effects of repeated quizzing (known as test-enhanced learning) and repeated studying on that retention. Methods: Participants were recruited from 4 annual meeting courses. All participants took a pretest. This randomized, controlled trial utilized a within-subjects design in which each participant experienced 3 different postcourse activities with each activity performed on different material. Each key information point from the course was randomized in a counterbalanced fashion among participants to one of the 3 activities: repeated short-answer quizzing, repeated studying, and no further exposure to the materials. A final test covering all information points from the course was taken 5.5 months after the course. Results: Thirty-five participants across the 4 courses completed the study. Average score on the pretest was 36%. Performance on the final test showed that repeated quizzing led to significantly greater long-term retention relative to both repeated studying (55% vs 46%; t[34] = 3.28, SEM = 0.03, p = 0.01, d = 0.49) and no further exposure (55% vs 44%; t[34] = 3.16, SEM = 0.03, p = 0.01, d = 0.58). Relative to the pretest baseline, repeated quizzing helped participants to retain almost twice as much of the knowledge acquired from the course compared to repeated studying or no further exposure. Conclusions: Whereas annual meeting continuing medical education (CME) courses lead to long-term gains in knowledge, when repeated quizzing is added, retention is significantly increased. CME planners may consider adding repeated quizzing to increase the impact of their courses. PMID:25609761

  12. 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.

  13. 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.

  14. 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.

  15. Physical activity enhances long-term quality of life in older adults: efficacy, esteem, and affective influences.

    PubMed

    Elavsky, Steriani; McAuley, Edward; Motl, Robert W; Konopack, James F; Marquez, David X; Hu, Liang; Jerome, Gerald J; Diener, Ed

    2005-10-01

    Physical activity has been effective in enhancing quality of life (QOL) of older adults over relatively short periods of time. However, little is known about the long-term effects of physical activity and even less about the possible mediators of this relationship. We examined the mediating effects of psychological variables on the relationship between physical activity and global QOL (satisfaction with life) in older adults over a 4-year period. Participants (N = 174, M age = 66.7 years) completed a battery of psychosocial measures at 1 and 5 years following enrollment in a 6-month randomized controlled exercise trial. Panel analysis conducted within a covariance modeling framework indicated that physical activity was related to self-efficacy, physical self-esteem, and positive affect at 1 year, and in turn, greater levels of self-efficacy and positive affect were associated with higher levels of QOL. Analyses indicated that changes in physical activity over the 4-year period were related to increases in physical self-esteem and positive affect, but only positive affect directly influenced improvements in QOL. The findings lend support to the position that physical activity effects on QOL are in part mediated by intermediate psychological outcomes and that physical activity can have long-term effects on well-being.

  16. 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.

  17. 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.

  18. 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.

  19. Sustained photosynthetic performance of Coffea spp. under long-term enhanced [CO2].

    PubMed

    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

  20. 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

  1. 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

  2. Perceived Impeding Factors for Return-to-Work after Long-Term Sickness Absence Due to Major Depressive Disorder: A Concept Mapping Approach

    PubMed Central

    de Vries, Gabe; Hees, Hiske L.; Koeter, Maarten W. J.; Lagerveld, Suzanne E.; Schene, Aart H.

    2014-01-01

    Objective The purpose of the present study was to explore various stakeholder perspectives regarding factors that impede return-to-work (RTW) after long-term sickness absence related to major depressive disorder (MDD). Methods Concept mapping was used to explore employees', supervisors' and occupational physicians' perspectives on these impeding factors. Results Nine perceived themes, grouped in three meta-clusters were found that might impede RTW: Person, (personality / coping problems, symptoms of depression and comorbid (health) problems, employee feels misunderstood, and resuming work too soon), Work (troublesome work situation, too little support at work, and too little guidance at work) and Healthcare (insufficient mental healthcare and insufficient care from occupational physician). All stakeholders regarded personality/coping problems and symptoms of depression as the most important impeding theme. In addition, supervisors emphasized the importance of mental healthcare underestimating the importance of the work environment, while occupational physicians stressed the importance of the lack of safety and support in the work environment. Conclusions In addition to the reduction of symptoms, more attention is needed on coping with depressive symptoms and personality problems in the work environment support in the work environment and for RTW in mental healthcare, to prevent long term sickness absence. PMID:24454786

  3. A pilot trial of acceptance and commitment therapy for symptoms of depression and anxiety in older adults residing in long-term care facilities.

    PubMed

    Davison, Tanya E; Eppingstall, Barbara; Runci, Susannah; O'Connor, Daniel W

    2017-07-01

    The aim of this study was to evaluate the efficacy and acceptability of a psychological intervention based on acceptance and commitment therapy (ACT) to improve symptoms of depression and anxiety among older adults living in long-term care. Forty one residents aged between 63 and 97 years (M = 85.3 years) participated in this study. Residents were allocated to receive either a 12 session ACT intervention implemented by trainee psychology therapists or a wait-list control group. Measures of depression and anxiety were collected at baseline and 8 week post-intervention, and residents who received the intervention were tracked for three months. A treatment satisfaction questionnaire was administered to residents who received the intervention and a sample of 10 facility staff members. Using an intention to treat approach and controlling for baseline scores, scores on depression measures were significantly lower after the ACT intervention than after the wait-list control. These outcomes were maintained at three-month follow-up. Treatment satisfaction was rated highly by both residents and their care staff. This preliminary trial suggests that ACT shows promise as a therapeutic approach to address symptoms of depression in long-term care.

  4. 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.

  5. 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

  6. 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. Copyright © 2014 Elsevier Inc. All rights reserved.

  7. The influence of patients' attributions of the immediate effects of treatment of depression on long-term effectiveness of behavioural activation and antidepressant medication.

    PubMed

    Moradveisi, Latif; Huibers, Marcus J H; Arntz, Arnoud

    2015-06-01

    Patients' attributions of effects of treatment are important, as these can affect long-term outcome. Most studies so far focused on the influence of attributions to medication for anxiety and depression disorders. We investigated the effects of patients' attributions made after acute treatment on the long-term outcome of antidepressant medication (ADM) and psychological treatment (behavioural activation, BA). Data are based on a randomized trial testing the effectiveness of BA vs. ADM for major depression (MDD) in Iran. Patients with MDD (N = 100) were randomized to BA (N = 50) or ADM (N = 50). Patients' attributions were assessed at post-test (after completion of the treatments). Scores on an attribution questionnaire were factor analysed, and factor scores were retained as predictors of depressive symptoms at 1-year follow-up. Regression analysis was used to test whether attributions predicted depressive symptoms at 1-yr follow-up, controlling for symptom level, condition, and their interaction at post-test. Belief in coping efficacy was the only attribution factor significantly predicting 1-year HRSD scores, controlling for condition, post-test HRSD and their interaction. It also mediated the condition differences at follow-up. Credit to self was the single attribution factor that predicted BDI follow-up scores, controlling for condition, posttest BDI, and their interaction. It partially mediated the condition differences on the BDI at follow-up. Attribution to increased coping capacities and giving credit to self appear essential. In the long-term (at 1 year follow-up), the difference in outcome between BA and ADM (with BA being superior to ADM) is at least partially mediated by attributions. Copyright © 2015 Elsevier Ltd. All rights reserved.

  8. Effects of short term and long term Extremely Low Frequency Magnetic Field on depressive disorder in mice: Involvement of nitric oxide pathway.

    PubMed

    Madjid Ansari, Alireza; Farzampour, Shahrokh; Sadr, Ali; Shekarchi, Babak; Majidzadeh-A, Keivan

    2016-02-01

    Previous reports on the possible effects of Extremely Low Frequency Magnetic Fields (ELF MF) on mood have been paradoxical in different settings while no study has yet been conducted on animal behavior. In addition, it was shown that ELF MF exposure makes an increase in brain nitric oxide level. Therefore, in the current study, we aimed to assess the possible effect(s) of ELF MF exposure on mice Forced Swimming Test (FST) and evaluate the probable role of the increased level of nitric oxide in the observed behavior. Male adult mice NMRI were recruited to investigate the short term and long term ELF MF exposure (0.5 mT and 50 Hz, single 2h and 2 weeks 2h a day). Locomotor behavior was assessed by using open-field test (OFT) followed by FST to evaluate the immobility time. Accordingly, NΩ-nitro-l-arginine methyl ester 30 mg/kg was used to exert anti-depressant like effect. According to the results, short term exposure did not alter the immobility time, whereas long term exposure significantly reduces immobility time (p<0.01). However, it was revealed that the locomotion did not differ among all experimental groups. Short term exposure reversed the anti-depressant like effect resulting from 30 mg/kg of NΩ-nitro-l-arginine methyl ester (p<0.01). It has been concluded that long term exposure could alter the depressive disorder in mice, whereas short term exposure has no significant effect. Also, reversing the anti-depressant activity of L-NAME indicates a probable increase in the brain nitric oxide. Copyright © 2016 Elsevier Inc. All rights reserved.

  9. 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.

  10. 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.

  11. Association of long-term patterns of depressive symptoms and attention/executive function among older men with and without human immunodeficiency virus.

    PubMed

    Armstrong, Nicole M; Surkan, Pamela J; Treisman, Glenn J; Sacktor, Ned C; Irwin, Michael R; Teplin, Linda A; Stall, Ron; Martin, Eileen M; Becker, James T; Munro, Cynthia; Levine, Andrew J; Jacobson, Lisa P; Abraham, Alison G

    2017-08-01

    Older HIV-infected men are at higher risk for both depression and cognitive impairments, compared to HIV-uninfected men. We evaluated the association between longitudinal patterns of depressive symptoms and attention/executive function in HIV-infected and HIV-uninfected men aged 50+ years to understand whether HIV infection influenced the long-term effect of depression on attention/executive function. Responses to the Center for Epidemiologic Studies-Depression scale and attention/executive function tests (Trail Making Test Part B and Symbol Digit Modalities Test) were collected semiannually from May 1986 to April 2015 in 1611 men. Group-based trajectory models, stratified by HIV status, were used to identify latent patterns of depressive symptoms and attention/executive function across 12 years of follow-up. We identified three depression patterns for HIV-infected and HIV-uninfected men (rare/never 50.0 vs. 60.6%, periodically depressed 29.6 vs. 24.5%, chronic high 20.5 vs.15.0%, respectively) and three patterns of attention/executive function for HIV-infected and HIV-uninfected men (worst-performing 47.4 vs. 45.1%; average 41.9 vs. 47.0%; best-performing 10.7 vs. 8.0%, respectively). Multivariable logistic regression models were used to assess associations between depression patterns and worst-performing attention/executive function. Among HIV-uninfected men, those in the periodically depressed and chronic high depressed groups had higher odds of membership in the worst-performing attention/executive function group (adjusted odds ratio [AOR] = 1.45, 95% CI 1.04, 2.03; AOR = 2.25, 95% CI 1.49, 3.39, respectively). Among HIV-infected men, patterns of depression symptoms were not associated with patterns of attention/executive function. Results suggest that HIV-uninfected, but not HIV-infected, men with chronic high depression are more likely to experience a long-term pattern of attention/executive dysfunction.

  12. Effects of maternal postpartum depression in a well-resourced sample: Early concurrent and long-term effects on infant cognitive, language, and motor development.

    PubMed

    Smith-Nielsen, Johanne; Tharner, Anne; Krogh, Marianne Thode; Vaever, Mette Skovgaard

    2016-12-01

    This study examined early and long-term effects of maternal postpartum depression on cognitive, language, and motor development in infants of clinically depressed mothers. Participants were 83 mothers and their full-term born children from the urban region of Copenhagen, Denmark. Of this group, 28 mothers were diagnosed with postnatal depression three to four months postpartum in a diagnostic interview. Cognitive, language, and motor development was assessed with the Bayley Scales of Infant and Toddler Development third edition, when the infants were 4 and 13 months of age. We found that maternal postpartum depression was associated with poorer cognitive development at infant age four months, the effect size being large (Cohen's d = 0.8) and with similar effects for boys and girls. At 13 months of age infants of clinical mothers did not differ from infants of non-clinical mothers. At this time most (79%) of the clinical mothers were no longer, or not again, depressed. These results may indicate that maternal depression can have an acute, concurrent effect on infant cognitive development as early as at four months postpartum. At the same time, in the absence of other risk factors, this effect may not be enduring. The main weaknesses of the study include the relatively small sample size and that depression scores were only available for 35 of the non-clinical mothers at 13 months. © 2016 Scandinavian Psychological Associations and John Wiley & Sons Ltd.

  13. 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.

  14. Long-term effects of psychotherapy on moderate depression: a comparative study of narrative therapy and cognitive-behavioral therapy.

    PubMed

    Lopes, Rodrigo T; Gonçalves, Miguel M; Fassnacht, Daniel B; Machado, Paulo P P; Sousa, Inês

    2014-01-01

    In a previous clinical controlled trial (Lopes et al., 2014), narrative therapy (NT) showed promising results in ameliorating depressive symptoms with comparable outcomes to cognitive-behavioral therapy (CBT) when patients completed treatment. This paper aims to assess depressive symptoms and interpersonal problems in this clinical sample at follow-up. Using the Beck Depression Inventory-II and Outcome Questionnaire-45.2 Interpersonal Relations Scale, naturalistic prospective follow-up assessment was conducted at 21 and 31 months after the last treatment session. At follow-up, patients kept improving in terms of depressive symptoms and interpersonal problems. The odds that a patient maintained recovery from depressive symptoms at follow-up were five times higher than the odds that a patient maintained recovery from interpersonal problems. In the same way, the odds of a patient never recovering from interpersonal problems were five times higher than the odds of never recovering from depressive symptoms. The study did not control for the natural course of depression or treatment continuation. For depressed patients with greater interpersonal disabilities, longer treatment plans and alternative continuation treatments should be considered. Copyright © 2014 Elsevier B.V. All rights reserved.

  15. 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.

  16. 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.

  17. Long-term follow-up of a randomized controlled trial comparing acceptance and commitment therapy and standard cognitive behavior therapy for anxiety and depression.

    PubMed

    Forman, Evan M; Shaw, Jena A; Goetter, Elizabeth M; Herbert, James D; Park, Jennie A; Yuen, Erica K

    2012-12-01

    The present study represents one of the first comparisons of the long-term effectiveness of traditional cognitive behavior therapy (i.e., Beckian cognitive therapy; CT) and acceptance and commitment therapy (ACT). One hundred thirty-two anxious or depressed outpatients were randomly assigned to receive either CT or ACT, and were assessed at posttreatment (n=90) and at 1.5-year (n=91) follow-up. As previously reported, the two treatments were equivalently effective at posttreatment according to measures of depression, anxiety, overall (social/occupational/symptom-related) functioning, and quality of life. However, current results suggest that treatment gains were better maintained at follow-up in the CT condition. Clinical significance analyses revealed that, at follow-up, one-third more CT patients were in the clinically normative range in terms of depressive symptoms and more than twice as many CT patients were in the normative range in terms of functioning levels. The possible long-term advantage of CT relative to ACT in this population is discussed. Copyright © 2012. Published by Elsevier Ltd.

  18. 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

  19. 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

  20. Enhanced decomposition of stable soil organic carbon and microbial catabolic potentials by long-term field warming.

    PubMed

    Feng, Wenting; Liang, Junyi; Hale, Lauren E; Jung, Chang Gyo; Chen, Ji; Zhou, Jizhong; Xu, Minggang; Yuan, Mengting; Wu, Liyou; Bracho, Rosvel; Pegoraro, Elaine; Schuur, Edward A G; Luo, Yiqi

    2017-06-09

    Quantifying soil organic carbon (SOC) decomposition under warming is critical to predict carbon-climate feedbacks. According to the substrate regulating principle, SOC decomposition would decrease as labile SOC declines under field warming, but observations of SOC decomposition under warming do not always support this prediction. This discrepancy could result from varying changes in SOC components and soil microbial communities under warming. This study aimed to determine the decomposition of SOC components with different turnover times after subjected to long-term field warming and/or root exclusion to limit C input, and to test whether SOC decomposition is driven by substrate lability under warming. Taking advantage of a 12-year field warming experiment in a prairie, we assessed the decomposition of SOC components by incubating soils from control and warmed plots, with and without root exclusion for 3 years. We assayed SOC decomposition from these incubations by combining inverse modeling and microbial functional genes during decomposition with a metagenomic technique (GeoChip). The decomposition of SOC components with turnover times of years and decades, which contributed to 95% of total cumulative CO2 respiration, was greater in soils from warmed plots. But the decomposition of labile SOC was similar in warmed plots compared to the control. The diversity of C-degradation microbial genes generally declined with time during the incubation in all treatments, suggesting shifts of microbial functional groups as substrate composition was changing. Compared to the control, soils from warmed plots showed significant increase in the signal intensities of microbial genes involved in degrading complex organic compounds, implying enhanced potential abilities of microbial catabolism. These are likely responsible for accelerated decomposition of SOC components with slow turnover rates. Overall, the shifted microbial community induced by long-term warming accelerates the

  1. Long-term consequences of pubertal timing for youth depression: Identifying personal and contextual pathways of risk

    PubMed Central

    RUDOLPH, KAREN D.; TROOP-GORDON, WENDY; LAMBERT, SHARON F.; NATSUAKI, MISAKI N.

    2015-01-01

    This research explored sex differences in the pathways linking pubertal timing to depression across 4 years. A sample of 167 youth (M age = 12.41 years, SD = 1.19) and their caregivers completed measures of puberty and semistructured interviews of interpersonal stress and youth depression. Youth reported on psychological (negative self-focus, anxious arousal) and social–behavioral (coping) characteristics; parents reported on youths’ social–behavioral characteristics (withdrawal/social problems) and deviant peer affiliations. Early maturation predicted stable high trajectories of depression in girls; although early maturing boys showed low initial levels of depression, they did not differ from girls by the final wave of the study. Latent growth curve analyses identified several psychological, social–behavioral, and interpersonal pathways accounting for the contribution of pubertal timing to initial and enduring risk for depression in girls as well as emerging risk for depression in boys. These findings provide novel insight into multilevel processes accounting for sex differences in depression across the adolescent transition. PMID:25422971

  2. Prenatal ethanol exposure enhances NMDAR-dependent long-term potentiation in the adolescent female dentate gyrus.

    PubMed

    Titterness, Andrea K; Christie, Brian R

    2012-01-01

    The dentate gyrus (DG) is a region of the hippocampus intimately involved with learning and memory. Prenatal exposure to either stress or ethanol can reduce long-term potentiation (LTP) in the male hippocampus but there is little information on how these prenatal events affect LTP in the adolescent female hippocampus. Previous studies suggest that deleterious effects of PNEE can, in part, be mediated by corticosterone, suggesting that prenatal stress might further enhance any alterations to LTP induced PNEE. When animals were exposed to a combination of prenatal stress and PNEE distinct sex differences emerged. Exposure to ethanol throughout gestation significantly reduced DG LTP in adolescent males but enhanced LTP in adolescent females. Combined exposure to stress and ethanol in utero reduced the ethanol-induced enhancement of LTP in females. On the other hand, exposure to stress and ethanol in utero did not alter the ethanol-induced reduction of LTP in males. These results indicate that prenatal ethanol and prenatal stress produce sex-specific alterations in synaptic plasticity in the adolescent hippocampus. Copyright © 2010 Wiley Periodicals, Inc., Inc.

  3. Analysis of long-term cognitive-enhancing effects of bryostatin-1 on the rabbit (Oryctolagus cuniculus) nictitating membrane response.

    PubMed

    Wang, Desheng; Darwish, Deya S; Schreurs, Bernard G; Alkon, Daniel L

    2008-05-01

    Previous work demonstrated that protein kinase C (PKC) is implicated in learning and memory. This study investigated whether: (i) PKC activated by bryostatin-1 (Bryo) just before or just after sessions of classical conditioning was capable of enhancing classical conditioning of the rabbit nictitating membrane response; (ii) improved behavioral performance matched the time course of PKC activation induced by Bryo; and (iii) vitamin E (Vit E) enhanced the efficacy of Bryo. Paired rabbits received daily trace conditioning with a tone conditioned stimulus and a corneal air puff unconditioned stimulus. Unpaired rabbits received the same stimuli but in an explicitly unpaired manner. After trace conditioning, all rabbits received daily delay conditioning, and then tone intensity testing. Rabbits pretreated with 10 microg/kg Bryo every other day before a relatively simple trace conditioning task showed more conditioned responses (CRs) during the first 10 trials of each trace conditioning session and a higher likelihood of a CR on the first trial of each trace conditioning session than rabbits pretreated with the vehicle control. Rabbits either posttreated daily with 10 microg/kg Bryo or pretreated with Vit E and subjected to a difficult trace conditioning task showed increased CRs relative to the vehicle control. Neither Bryo nor Vit E or their combination altered nonassociative responding or altered sensitivity to the conditioned stimulus or unconditioned stimulus. These findings demonstrate Bryo has long-term enhancing effects on classical conditioning of the rabbit nictitating membrane response.

  4. 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. Crown Copyright 2009. Published by Elsevier B.V. All rights reserved.

  5. Socioeconomic position and depression in South African adults with long-term health conditions: a longitudinal study of causal pathways.

    PubMed

    Elwell-Sutton, T; Folb, N; Clark, A; Fairall, L R; Lund, C; Bachmann, M O

    2017-08-14

    There is convincing evidence that lower socioeconomic position is associated with increased risk of mental disorders. However, the mechanisms involved are not well understood. This study aims to elucidate the causal pathways between socioeconomic position and depression symptoms in South African adults. Two possible causal theories are examined: social causation, which suggests that poor socioeconomic conditions cause mental ill health; and social drift, which suggests that those with poor mental health are more likely to drift into poor socioeconomic circumstances. The study used longitudinal and cross-sectional observational data on 3904 adults, from a randomised trial carried out in 38 primary health care clinics between 2011 and 2012. Structural equation models and counterfactual mediation analyses were used to examine causal pathways in two directions. First, we examined social causation pathways, with language (a proxy for racial or ethnic category) being treated as an exposure, while education, unemployment, income and depression were treated as sequential mediators and outcomes. Second, social drift was explored with depression treated as a potential influence on health-related quality of life, job loss and, finally, income. The results suggest that the effects of language on depression at baseline, and on changes in depression during follow-up, were mediated through education and income but not through unemployment. Adverse effects of unemployment and job loss on depression appeared to be mostly mediated through income. The effect of depression on decreasing income appeared to be mediated by job loss. These results suggest that both social causation and social selection processes operate concurrently. This raises the possibility that people could get trapped in a vicious cycle in which poor socioeconomic conditions lead to depression, which, in turn, can cause further damage to their economic prospects. This study also suggests that modifiable factors such

  6. Long-term effects of cognitive therapy on biological rhythms and depressive symptoms: A randomized clinical trial.

    PubMed

    Mondin, Thaíse Campos; Cardoso, Taiane de Azevedo; Jansen, Karen; Silva, Giovanna Del Grande da; Souza, Luciano Dias de Mattos; Silva, Ricardo Azevedo da

    2015-11-15

    To evaluate the effect of cognitive therapy on biological rhythm and depressive and anxious symptoms in a twelve-month follow-up period. In addition, correlations between the reduction of depression and anxiety symptoms and the regulation of biological rhythm were observed. This was a randomized clinical trial with young adults from 18 to 29 years of age who were diagnosed with depression. Two models of psychotherapy were used: Cognitive Behavioral Therapy (CBT) and Narrative Cognitive Therapy (NCT). Biological rhythm was assessed with the Biological Rhythm Interview of Assessment in Neuropsychiatry (BRIAN). Severity of depressive and anxious symptoms was assessed by the Hamilton Depression Rating Scale (HDRS) and the Hamilton Anxiety Rating Scale (HARS), respectively. The sample included 97 patients who were divided within the protocols of psychotherapy. There was a significant reduction in depressive and anxious symptoms (p<0.001) and an increase on regulation of biological rhythm (p<0.05) at the twelve-month follow-up. Moreover, we showed a positive correlation between the reduction of depressive symptoms and regulation of biological rhythm (r=0.638; p<0.001) and between the reduction of anxious symptoms and regulation of biological rhythm (r=0.438; p<0.001). Both models showed that cognitive therapy was effective on the reduction of depressive and anxious symptoms and on the regulation of biological rhythm at a twelve-month follow-up evaluation. This study highlights the association between biological rhythm and symptoms of depression and anxiety. We did not assess genetic, hormonal or neurochemical factors and we did not include patients under pharmaceutical treatment or those with severe symptomatology. Copyright © 2015 Elsevier B.V. All rights reserved.

  7. Safety and efficacy of olanzapine in the long-term treatment of Japanese patients with bipolar I disorder, depression: an integrated analysis.

    PubMed

    Katagiri, Hideaki; Tohen, Mauricio; McDonnell, David P; Fujikoshi, Shinji; Case, Michael; Kanba, Shigenobu; Takahashi, Michihiro; Gomez, Juan-Carlos

    2014-07-01

    Safety and efficacy of long-term olanzapine treatment in Japanese patients with bipolar depression were assessed. An integrated analysis of data from two studies was performed in olanzapine-treated patients (n = 165) with bipolar depression. Study 1 was a 6-week, double-blind, global study. Patients were randomly assigned to olanzapine or placebo followed by 18 weeks of open-label treatment. Study 2 was an open-label extension of Study 1 involving only Japanese patients. Patients assigned to Pre-olanzapine and Pre-placebo in Study 1 were treated for 24 weeks (total olanzapine exposure 42 or 48 weeks) and newly recruited patients (New-olanzapine) were treated for 48 weeks. Safety outcomes included treatment-emergent adverse events and changes in metabolic parameters. Efficacy outcome was assessed with Montgomery-Åsberg Depression Rating Scale score. Forty-three percent of patients completed the 42- or 48-week olanzapine treatment period. The most common treatment-emergent adverse event was weight increased (47.9%). Significant increases were seen in weight (3.5 kg), and in fasting glucose (3.5 mg/dL), fasting total cholesterol (8.1 mg/dL), and fasting triglycerides (35.1 mg/dL). Remission rates (Montgomery-Åsberg Depression Rating Scale total score ≤12 at any time) were 79.8% for the Pre-olanzapine group, 90.2% for the Pre-placebo group, and 85.0% for the New-olanzapine group. No patents developed mania during treatment. Long-term use of olanzapine in a Japanese population with bipolar depression is associated with increases in weight and fasting metabolic measures, and also with improved depressive symptoms with avoidance of mania. Clinicians must carefully consider the benefits and risks of long-term therapy with olanzapine. © 2014 The Authors. Psychiatry and Clinical Neurosciences © 2014 Japanese Society of Psychiatry and Neurology.

  8. Three-Year long-term outcome of 458 naturalistically treated inpatients with major depressive episode: severe relapse rates and risk factors.

    PubMed

    Seemüller, Florian; Meier, Sebastian; Obermeier, Michael; Musil, Richard; Bauer, Michael; Adli, Mazda; Kronmüller, Klaus; Holsboer, Florian; Brieger, Peter; Laux, Gerd; Bender, Wolfram; Heuser, Isabella; Zeiler, Joachim; Gaebel, Wolfgang; Riedel, Michael; Falkai, Peter; Möller, Hans-Jürgen

    2014-10-01

    In randomized controlled trials, maintenance treatment for relapse prevention has been proven to be efficacious in patients responding in acute treatment, its efficacy in long-term outcome in "real-world patients" has yet to be proven. Three-year long-term data from a large naturalistic multisite follow-up were presented. Severe relapse was defined as suicide, severe suicide attempt, or rehospitalization. Next to relapse rates, possible risk factors including antidepressant medication were identified using univariate generalized log-rank tests and multivariate Cox proportional hazards model for time to severe relapse. Overall data of 458 patients were available for analysis. Of all patients, 155 (33.6%) experienced at least one severe relapse during the 3-year follow-up. The following variables were associated with a shorter time to a severe relapse in univariate and multivariate analyses: multiple hospitalizations, presence of avoidant personality disorder, continuing antipsychotic medication, and no further antidepressant treatment. In comparison with other studies, the observed rate of severe relapse during 3-year period is rather low. This is one of the first reports demonstrating a beneficial effect of long-term antidepressant medication on severe relapse rates in naturalistic patients. Concomitant antipsychotic medication may be a proxy marker for treatment resistant and psychotic depression.

  9. 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. Copyright © 2015 Elsevier Ltd. All rights reserved.

  10. 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.

  11. Enhancement of root respiration and photosynthesis in Quercus serrata Thunb. seedlings by long-term aluminum treatment.

    PubMed

    Tomioka, Rie; Takenaka, Chisato

    2007-01-01

    In this article, we discuss the effects of long-term (17 months) aluminum (Al) treatment on the growth, root respiration rate, nutrient uptake rate, and photosynthetic activity of two-year-old Quercus serrata Thunb. seedlings. The seedlings were cultivated by supplying a nutrient solution with or without Al twice a week for 17 months in siliceous sand. After 5- and 17-month treatments, growth, root respiration rate, photosynthetic activity, and the concentration of minerals in the roots and leaves were measured. Al treatment for 5 and 17 months markedly enhanced the growth and photosynthetic activity, and Al treatment for 17 months stimulated the root respiration rate. Although Al treatment for 17 months significantly decreased the Ca, Mg, and P concentrations in leaves, this decrease did not cause deficiency symptoms because of significant increases in shoot biomass and photosynthetic activity. The results of this study reveal that an increase in photosynthetic activity supports growth enhancement induced by Al treatment in Q. serrata seedlings, and suggest that Al may act as a trigger in activating some metabolic functions that can induce growth.

  12. 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

  13. Long-term safety and efficacy of armodafinil in bipolar depression: A 6-month open-label extension study.

    PubMed

    Ketter, Terence A; Amchin, Jess; Frye, Mark A; Gross, Nicholas

    2016-06-01

    Safe/well-tolerated treatments for bipolar I depression remain limited. We assessed safety/tolerability of adjunctive open-label armodafinil, a wakefulness-promoting agent evaluated in 3 acute, controlled efficacy studies with variable efficacy results. Completers of three 8-week, double-blind, placebo-controlled adjunctive armodafinil studies (150-200 mg/day added to ongoing stable maintenance doses of 1 or 2 protocol-defined mood stabilizers) in bipolar I depression could enter this 6-month, open-label extension study. Objectives included evaluation of safety/tolerability (primary) and efficacy (secondary). 867 patients enrolled; 863 received ≥1 dose of armodafinil and 506 (58%) completed the 6-month study. Headache, insomnia, and anxiety were the most common adverse events (AEs) reported, whereas akathisia, nausea, sedation/somnolence, and weight increase were uncommon. Mean measures assessing emergence of mania, anxiety, insomnia, or suicidality showed no worsening. Discontinuations due to AEs occurred in 57 (7%) patients. Serious AEs occurred in 27 (3%) patients and were considered treatment-related in 8 (1%) patients. Depressive symptoms improved over the 6 months, as did patient functioning. Lack of placebo control. Adjunctive armodafinil was generally safe and well tolerated over 6 months of open-label treatment at 150-200 mg/day when taken with protocol-defined mood stabilizers for bipolar I depression. This 6-month open-label study suggested that armodafinil augmentation of bipolar maintenance therapies may have a favorable risk profile and may improve depressive symptoms in some patients with bipolar I depression. Copyright © 2016 Elsevier B.V. All rights reserved.

  14. 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 ...

  15. Development of the psychometric property of a Minimum Data-Set-Based Depression Rating Scale for use in long-term care facilities in Taiwan.

    PubMed

    Hsiao, C Y; Lan, C F; Chang, P L; Li, I C

    2015-01-01

    Our aim is to develop the psychometric property of the Minimum Data-Set-Based Depression Rating Scale (MDS-DRS) to ensure its use to assess service needs and guide care plans for institutionalized residents. 378 residents were recruited from the Haoran Senior Citizen Home in northern Taiwan. The MDS-DRS and GDS-SF were used to identify observable features of depression symptoms in the elderly residents. A total of 378 residents participated in this study. The receiver operating characteristic (ROC) curve indicated that the MDS-DRS has a 43.3% sensitivity and a 90.6% specificity when screening for depression symptoms. The total variance, explained by the two factors 'sadness' and 'distress,' was 58.1% based on the factor analysis. Reliable assessment tools for nurses are important because they allow the early detection of depression symptoms. The MDS-DRS items perform as well as the GDS-SF items in detecting depression symptoms. Furthermore, the MDS-DRS has the advantage of providing information to staff about care process implementation, which can facilitate the identification of areas that need improvement. Further research is needed to validate the use of the MDS-DRS in long-term care facilities.

  16. 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

    Matcham, Faith; Norton, Sam; Scott, David L; Steer, Sophia; Hotopf, Matthew

    2016-02-01

    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. Secondary analysis of clinical trial data was performed. Data were collected at baseline and at 6-monthly intervals for 2 years. The EuroQoL (EQ-5D(TM)) 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. 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. 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. © The Author 2015. Published by Oxford University Press on behalf of the British Society for Rheumatology.

  17. 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

  18. Long-term effects of early adolescent methamphetamine exposure on depression-like behavior and the hypothalamic vasopressin system in mice.

    PubMed

    Joca, Lauren; Zuloaga, Damian G; Raber, Jacob; Siegel, Jessica A

    2014-01-01

    Methamphetamine (MA) has neurotoxic effects on the adult human brain that can lead to deficits in behavior and cognition. However, relatively little research has examined the behavioral or neurotoxic effects of MA in adolescents. The rising rates of adolescent MA use make it imperative that we understand the long-term effects of MA exposure on the adolescent brain and how these effects may differ from those seen in adults. In this study, the long-term effects of MA exposure during early adolescence on behavior and the vasopressin system in the paraventricular nucleus of the hypothalamus in late adolescent and adult male and female C57BL/6J mice were examined. MA exposure increased depression-like behavior in the Porsolt forced swim test in both late adolescent and adult male and female mice. Late adolescent male mice exposed to MA also showed a decrease in the number of vasopressin-immunoreactive neurons in the paraventricular nucleus compared to sex-matched saline-treated controls. Thus, similar to humans exposed to MA during adolescence, mice exposed to MA during adolescence show increased depression-like behavior later in life. These changes in behavior may be related to MA-induced alterations in vasopressin and the hypothalamic-pituitary-adrenal axis, especially in males. 2014 S. Karger AG, Basel

  19. 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

  20. 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.

  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. Long-Term Outcome of a School-Based, Universal Approach to Prevention of Depression in Adolescents

    ERIC Educational Resources Information Center

    Spence, Susan H.; Sheffield, Jeanie K.; Donovan, Caroline L.

    2005-01-01

    In this study, the authors examined the 2-, 3-, and 4-year outcomes of a school-based, universal approach to the prevention of adolescent depression. Despite initial short-term positive effects, these benefits were not maintained over time. Adolescents who completed the teacher-administered cognitive-behavioral intervention did not differ…

  3. 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

  4. Utilizing quality improvement methods to prevent falls and injury from falls: enhancing resident safety in long-term care.

    PubMed

    MacLaurin, Anne; McConnell, Heather

    2011-12-01

    Internationally, the growing evidence related to preventable adverse events within healthcare settings has resulted in the creation of numerous patient safety and quality improvement initiatives. In Canada, Safer Healthcare Now!, a national patient safety initiative of the Canadian Patient Safety Institute, and the Registered Nurses' Association of Ontario, the professional association representing registered nurses in Ontario, have partnered to combine quality improvement expertise with evidence-based practice expertise to accelerate improvement in the area of falls prevention and injury reduction. The synergistic relationship between Safer Healthcare Now! and the Registered Nurses' Association of Ontario has resulted in the evolution of the Safer Healthcare Now! national Falls Prevention intervention. The ultimate goal of the Falls Prevention intervention is to improve care by translating "what we know" into "what we do," by supporting quality improvement teams to make changes at the local level to enhance the patient experience. This article provides an overview of Safer Healthcare Now! as a national patient safety initiative, and highlights the results of a National Collaborative on Falls Prevention as a knowledge translation strategy utilized within the long-term care setting. A description of expanding supports for knowledge translation will also be provided. Copyright © 2011 National Safety Council and Elsevier Ltd. All rights reserved.

  5. 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. Copyright © 2013 Elsevier Ltd. All rights reserved.

  6. 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.

  7. 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.

  8. Long-Term Treatment with Egg Oral Immunotherapy Enhances Sustained Unresponsiveness That Persists After Cessation of Therapy

    PubMed Central

    Jones, Stacie M.; Burks, A. Wesley; Keet, Corinne; Vickery, Brian P.; Scurlock, Amy M.; Wood, Robert A.; Liu, Andrew H.; Sicherer, Scott H.; Henning, Alice K.; Lindblad, Robert W.; Dawson, Peter; Berin, Cecilia; Fleischer, David M.; Leung, Donald Y. M.; Plaut, Marshall; Sampson, Hugh A.

    2016-01-01

    Background We previously reported results of a randomized, placebo-controlled study of egg oral immunotherapy (eOIT), in which 27.5% of subjects achieved sustained unresponsiveness (SU) after 2 years. Here we report results of treatment through 4 years and long-term follow-up. Objective To evaluate the efficacy and safety of eOIT in participants treated up to 4 years. Methods Egg-allergic children (5–18 y/o) received eOIT (n=40) for up to 4 years or placebo (n=15) ≤1 year. The key outcome was the percentage of subjects achieving SU by Year 4. Safety and immunologic assessments were performed, and long-term follow-up questionnaires were administered after study conclusion (LFQ-1) and 1 year later (LFQ-2). Results Of 40 eOIT-treated subjects, 20/40 (50.0%) demonstrated SU by Year 4. For those subjects still dosing during Years 3–4, mild symptoms were present in 12/22 (54.5%) subjects. At the time of LFQ, more eOIT subjects [LFQ-1 23/34 (68%); LFQ-2 21/33 (64%)] were consuming unbaked and baked egg vs. placebos [LFQ-1 2/11(18%), p=0.006; LFQ-2 3/12 (25%), p=0.04]. Of subjects achieving SU, 18/20 (90%) completed the LFQ with 18/18 (100%) reporting consumption of all forms of egg. When compared to subjects not achieving SU, subjects achieving SU had higher IgG4 values (p=0.001) and lower egg skin prick test scores (p=0.0002) over time and a lower median baseline ratio of egg-specific IgE to total IgE (1.1% vs. 2.7%, p=0.04). Conclusions SU following egg OIT is enhanced with longer duration of therapy, and increases the likelihood of tolerating unbaked egg in the diet. PMID:26924470

  9. Using Quality Improvement Principles to Enhance Long-Term Completion of Patient-Reported Outcomes after Ventral Hernia Repair.

    PubMed

    Ganesh Kumar, Nishant; Faqih, Adil A; Feng, Michael P; Miller, Richard S; Pierce, Richard A; Sharp, Kenneth W; Holzman, Michael D; Poulose, Benjamin K

    2017-02-01

    Ventral hernia repair (VHR) is a commonly performed surgical procedure. Unfortunately, long-term prospective information about quality of life and outcomes after VHR has been challenging to obtain. Decoupling follow-up from clinical visits via patient-reported outcomes (PROs) has been proposed as a means of achieving better long-term assessments after VHR. The Americas Hernia Society Quality Collaborative (AHSQC) is a national quality improvement (QI) effort in hernia repair that uses PROs to obtain long-term follow-up. However, the modality of PRO engagement to maximize participation has not been well established. A formal QI initiative was undertaken to determine if long-term PRO follow-up could be increased at a single AHSQC site by adding telephone communication to email communication for long-term postoperative VHR assessment. Between September 2015 and July 2016, the long-term (greater than 1 year) AHSQC PRO completion rates after VHR at our institution were analyzed using plan-do-study-act cycles. Two interventions were implemented: contacting patients by telephone and changing timing of telephone calls. Two hundred thirty-two patients were identified, of whom 99 (42.7%) met eligibility criteria. Before this initiative, the long-term PRO completion rate was 16.3% in postoperative VHR patients. The completion rate after introducing telephone calls (intervention 1) was 35.7% and after changing the timing of telephone calls (intervention 2), was 55.1%. The mean participation rate was 45.4% (± 9.7%). A telephone-based approach markedly improved long-term PRO participation rates in postoperative VHR patients. Ultimately, a combination of email and telephone communication may be necessary to achieve higher levels of PRO follow-up in the VHR population. Copyright © 2016 American College of Surgeons. All rights reserved.

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

    PubMed Central

    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

    2010-01-01

    Objective We examine remission rate probabilities, recovery rates, and residual symptoms across 36 weeks in the Treatment for Adolescents with Depression Study (TADS). Method TADS, a multisite clinical trial, randomized 439 adolescents with major depressive disorder (MDD) to 12 weeks of treatment to fluoxetine (FLX), cognitive behavioral therapy (CBT), their combination (COMB), or pill placebo (PBO). The PBO group, treated openly after week 12, was not included in the subsequent analyses. Treatment differences in remission rates and probabilities of remission over time are compared. Recovery rates in remitters at week 12 (acute phase remitters) and week 18 (continuation phase remitters) are summarized. We also examined whether residual symptoms at the end of 12 weeks of acute treatment predicted later remission. Results At Week 36, the estimated remission rates for intention-to-treat cases were: COMB: 60%, FLX: 55%; CBT: 64%; overall: 60%. Paired comparisons reveal that at week 24 all active treatments converge on remission outcomes. The recovery rate at Week 36 was 65% for acute phase remitters and 71% for continuation phase remitters, with no significant between-treatment differences in recovery rates. Residual symptoms at the end of acute treatment predicted failure to achieve remission at weeks 18 and 36. Conclusions The majority of depressed adolescents in all three treatment modalities achieved remission at the end of nine months of treatment. PMID:19127172

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

    PubMed

    Boutry, Claire; El-Kadi, Samer W; Suryawan, Agus; Steinhoff-Wagner, Julia; Stoll, Barbara; Orellana, Renán A; Nguyen, Hanh V; Kimball, Scot R; Fiorotto, Marta L; Davis, Teresa A

    2016-04-15

    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 shown previously that pulsatile administration of leucine during continuous feeding over 24 h via orogastric tube enhanced protein synthesis in skeletal muscle compared with continuous feeding alone. To determine the long-term effects of leucine pulses, neonatal piglets (n = 11-12/group) were continuously fed formula via orogastric tube for 21 days, with an additional parenteral infusion of either leucine (CON + LEU; 800 μmol·kg(-1)·h(-1)) or alanine (CON + ALA) for 1 h every 4 h. The results show that body and muscle weights and lean gain were ∼25% greater, and fat gain was 48% lower in CON + LEU than CON + ALA; weights of other tissues were unaffected by treatment. Fractional protein synthesis rates in longissimus dorsi, gastrocnemius, and soleus muscles were ∼30% higher in CON + LEU compared with CON + ALA and were associated with decreased Deptor abundance and increased mTORC1, mTORC2, 4E-BP1, and S6K1 phosphorylation, SNAT2 abundance, and association of eIF4E with eIF4G and RagC with mTOR. There were no treatment effects on PKB, eIF2α, eEF2, or PRAS40 phosphorylation, Rheb, SLC38A9, v-ATPase, LAMTOR1, LAMTOR2, RagA, RagC, and LAT1 abundance, the proportion of polysomes to nonpolysomes, or the proportion of mRNAs encoding rpS4 or rpS8 associated with polysomes. Our results demonstrate that pulsatile delivery of a leucine supplement during 21 days of continuous enteral feeding enhances lean growth by stimulating the mTORC1-dependent translation initiation pathway, leading to protein synthesis in skeletal muscle of neonates.

  12. 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.

  13. 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).

  14. 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

  15. 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

  16. A multi-wave study of organizational justice at work and long-term sickness absence among employees with depressive symptoms.

    PubMed

    Hjarsbech, Pernille U; Christensen, Karl Bang; Bjorner, Jakob B; Madsen, Ida E H; Thorsen, Sannie V; Carneiro, Isabella G; Christensen, Ulla; Rugulies, Reiner

    2014-03-01

    Mental health problems are strong predictors of long-term sickness absence (LTSA). In this study, we investigated whether organizational justice at work - fairness in resolving conflicts and distributing work - prevents risk of LTSA among employees with depressive symptoms. In a longitudinal study with five waves of data collection, we examined a cohort of 1034 employees with depressive symptoms. Depressive symptoms and organizational justice were assessed by self-administered questionnaires and information on LTSA was derived from a national register. Using Poisson regression analyses, we calculated rate ratios (RR) for the prospective association of organizational justice and change in organizational justice with time to onset of LTSA. All analyses were sex stratified. Among men, intermediate levels of organizational justice were statistically significantly associated with a decreased risk of subsequent LTSA after adjustment for covariates [RR 0.49, 95% confidence interval (95% CI) 0.26-0.91]. There was also a decreased risk for men with high levels of organizational justice although these estimates did not reach statistical significance after adjustment (RR 0.47, 95% CI 0.20-1.10). We found no such results for women. In both sexes, neither favorable nor adverse changes in organizational justice were statistically significantly associated with the risk of LTSA. This study shows that organizational justice may have a protective effect on the risk of LTSA among men with depressive symptoms. A protective effect of favorable changes in organizational justice was not found.

  17. Metabotropic glutamate receptor, mGlu5, mediates enhancements of hippocampal long-term potentiation after environmental enrichment in young and old mice.

    PubMed

    Buschler, Arne; Manahan-Vaughan, Denise

    2017-03-15

    The metabotropic glutamate (mGlu) receptor, mGlu5, is of particular relevance for hippocampal function. It is critically required for the expression of long-term potentiation (LTP) and long-term depression (LTD), regulates neuronal oscillations, maintains the stability of place fields and is required for hippocampus-dependent memory. MGlu5-dysfunctions are associated with profound cognitive deficits in humans, and mGlu5 has been targeted as a putative cognitive enhancer. Cognitive enhancement, by means of environmental enrichment (EE) in rodents, results in improved hippocampal synaptic plasticity and memory. Here, we explored whether mGlu5 contributes to these enhancements. MGlu5-antagonism dose-dependently impaired the early phase of LTP (>4 h) in the CA1 region of young(3-4 month old) mice. Late-LTP (>24 h) was also impaired. LTP (>24 h) elicited in old (10-14 month old) mice displayed reduced sensitivity to mGlu5 antagonism. Short-term potentiation (STP, < 2 h) that was elicited by weaker afferent stimulation was unaffected by mGlu5-antagonism in both age-groups. EE significantly amplified STP (<2 h) in old and young animals, but did not increase the duration of synaptic potentiation, or promote induction of LTP. The improvement in STP was prevented by mGlu5-antagonism, in both young and old animals. These results indicate that modifications of the synapse that underlie improvements of LTP by EE require the contribution of mGlu5. Strikingly, although LTP in old mice does not critically depend on mGlu5, improvements in synaptic potentiation resulting from EE are mGlu5-dependent in old mice. Regarded in light of the known role for mGlu5 in hippocampal function and pathophysiology, these data suggest that mGlu5 regulation of synaptic information storage is pivotal to optimal hippocampal function. This article is part of the Special Issue entitled 'Metabotropic Glutamate Receptors, 5 years on'. Copyright © 2017 Elsevier Ltd. All rights reserved.

  18. Major Depression as a Predictor of Poor Long-Term Survival in a Brazilian Stroke Cohort (Study of Stroke Mortality and Morbidity in Adults) EMMA study.

    PubMed

    de Mello, Roberta Ferreira; Santos, Itamar de Souza; Alencar, Airlane Pereira; Benseñor, Isabela Martins; Lotufo, Paulo Andrade; Goulart, Alessandra Carvalho

    2016-03-01

    The influence of poststroke depression on long-term survival is poorly investigated. Thus, we aimed to evaluate the influence of major depression disorder (MDD) on long-term survival in the participants from The Study of Stroke Mortality and Morbidity in Adults (EMMA Study) in São Paulo, Brazil. We prospectively evaluated ischemic and hemorrhagic stroke (HS) cases from the EMMA Study. Baseline and stroke characteristics and cardiovascular risk factors were evaluated according to MDD assessed by the Patient Health Questionnaire, which was applied 30 days after index event and periodically during 1-year follow-up. We performed Kaplan-Meier survival analysis, as well as crude and multiple Cox proportional hazards models. In this subset of the EMMA Study, we evaluated 164 (85.9%) patients with ischemic stroke and 27 (14.1%) with HS. Among these, overall incidence of MDD was 25.1% during 1 year of follow-up, regardless stroke subtype. The peak rate of major depression postacute event was beyond 1 month. We observed a lower survival rate among individuals who developed poststroke MDD than among those who did not develop this condition after 1 year of follow-up (85.4% versus 96.5%, log rank P = .006). After multiple analysis, we kept a higher risk of all-cause mortality among those who developed MDD compared to participants without MDD (hazard ratio = 4.60, 95% confidence interval = 1.36-15.55, P = .01). Our findings suggest that incident MDD is a potential marker of poor prognosis 1 year after stroke. Copyright © 2016 National Stroke Association. Published by Elsevier Inc. All rights reserved.

  19. Efficacy of Desvenlafaxine 50 mg/d Versus Placebo in the Long-Term Treatment of Major Depressive Disorder: A Randomized, Double-Blind Trial

    PubMed Central

    Vialet, Cécile; Hwang, Eunhee; Tourian, Karen A.

    2015-01-01

    Objective: To examine long-term (11-month) antidepressant efficacy of desvenlafaxine 50 mg/d across a broad range of clinical and functional outcomes in patients with major depressive disorder. Method: Adult outpatients (≥ 18 years) with major depressive disorder (DSM-IV criteria) and a 17-item Hamilton Depression Rating Scale (HDRS-17) total score ≥ 20 at screening and baseline who responded to 8 weeks of open-label desvenlafaxine 50 mg/d and had a continuing stable response through week 20 were randomly assigned to receive placebo or desvenlafaxine 50 mg/d in a 6-month, double-blind, randomized withdrawal period. Depressive symptoms were evaluated using the HDRS-17, 6-item HDRS, and Clinical Global Impressions–Severity of Ilness and –Improvement (CGI-S, CGI-I). Health outcomes included the Work Productivity and Activity Impairment (WPAI) questionnaire and the World Health Organization 5-Item Well-Being Index (WHO-5). The trial was conducted from June 2009 to March 2011 at 87 study sites in 14 countries worldwide. Results: Of 874 patients enrolled in open-label treatment, 548 patients were randomly assigned to receive double-blind placebo (n = 276) or desvenlafaxine 50 mg/d (n = 272). At the end of the 6-month double-blind treatment, improvements in depressive symptoms were better maintained among the desvenlafaxine- than placebo-treated patients on all efficacy endpoints (all P ≤ .001); in the desvenlafaxine group, 21.8% (vs 42.9% in the placebo group) had CGI-I ratings of 5, 6, and 7 (minimally worse/much worse/very much worse), and 74.4% met criteria for remission (placebo: 54.2%). WPAI and WHO-5 scores indicated significantly better productivity and well-being with continued desvenlafaxine (vs placebo, P ≤ .001). Conclusions: Long-term treatment with desvenlafaxine 50 mg/d maintained improvements in major depressive disorder among adult outpatients who exhibited a stable therapeutic response. Trial Registration: ClinicalTrials.gov identifier: NCT

  20. Chronic social defeat induces long-term behavioral depression of aggressive motivation in an invertebrate model system.

    PubMed

    Rose, Jacqueline; Rillich, Jan; Stevenson, Paul A

    2017-01-01

    Losing a fight against a conspecific male (social defeat) induces a period of suppressed aggressiveness and general behaviour, often with symptoms common to human psychiatric disorders. Agonistic experience is also discussed as a potential cause of consistent, behavioral differences between individuals (animal "personality"). In non-mammals, however, the impact of single agonistic encounters typically last only hours, but then again studies of repeated intermittent defeat (chronic social defeat) are seldom. We report the effect of chronic social defeat in adult male crickets (Gryllus bimaculatus), for which all known behavioral effects of defeat last only 3 h. Firstly, after 48 h social isolation, crickets that experienced 5 defeats at 24 h intervals against the same, weight-matched opponent exhibited suppressed aggressiveness lasting >24 h, which was still evident when the animals were matched against an unfamiliar opponent at the last trial. Secondly, this longer-term depression of aggression also occurred in 48 h isolated crickets that lost 6 fights at 1 h intervals against unfamiliar opponents at each trial. Thirdly, crickets isolated as larvae until adult maturity (>16 days) were significantly more aggressive, and less variable in their aggressiveness at their very first fight than 48 h isolates, and also significantly more resilient to the effects of chronic social defeat. We conclude that losing an aggressive encounter in crickets has a residual effect, lasting at least 24 h, that accumulates when repeated defeats are experienced, and leads to a prolonged depression of aggressive motivation in subordinates. Furthermore, our data indicate that social interactions between young adults and possibly larvae can have even longer, possibly lifelong influences on subsequent behavior. Social subjugation is thus likely to be a prime determinant of inter-individual behavioral differences in crickets. Our work also opens new avenues for investigating proximate

  1. 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.

  2. 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. Copyright © 2014 The Authors. Published by Elsevier B.V. All rights reserved.

  3. 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

  4. Long-term functioning and sleep quality in patients with major depressive disorder treated with extended-release quetiapine fumarate.

    PubMed

    Sheehan, David V; Locklear, Julie; Svedsäter, Henrik; Datto, Catherine

    2012-09-01

    The aim of this study was to assess patients' functioning and sleep quality during extended-release quetiapine fumarate (quetiapine XR) maintenance treatment. A double-blind, randomized-withdrawal maintenance study of quetiapine XR monotherapy was carried out in patients with major depressive disorder. Following 4-8 weeks of open-label quetiapine XR and 12-18 weeks of open-label quetiapine XR stabilization (50, 150, or 300 mg/day), eligible patients were randomized to quetiapine XR (50, 150, or 300 mg/day) or placebo. Secondary variables of the Sheehan Disability Scale (SDS) and the Pittsburgh Sleep Quality Index (PSQI) were used to assess functioning and sleep quality and are reported here. Quetiapine XR significantly maintained functioning versus placebo. Changes in the least squares means (LSM) from randomization in the SDS total scores were as follows: -0.45, quetiapine XR (P<0.05), versus 0.44, placebo. Quetiapine XR significantly maintained SDS domains 'social life/leisure' (-0.19; P<0.05) and 'family life/home responsibilities' (-0.22; P<0.05) versus placebo (0.13 and 0.10, respectively). Quetiapine XR significantly maintained sleep quality (LSM change in PSQI total scores: 0.06, quetiapine XR vs. 1.35, placebo; P<0.001), with five of seven PSQI components being significant for quetiapine XR versus placebo. In conclusion, quetiapine XR (50-300 mg/day) monotherapy better maintains overall functioning and sleep quality than placebo in patients with major depressive disorder.

  5. 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

  6. 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

  7. 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

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

    PubMed

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

    2015-10-01

    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. Copyright © 2015 Elsevier Inc. All rights reserved.

  9. Long-term Effectiveness of Modified Electroconvulsive Therapy Compared With Repetitive Transcranial Magnetic Stimulation for the Treatment of Recurrent Major Depressive Disorder.

    PubMed

    Jin, Xi-Long; Xu, Wei-Qin; Le, Ya-Juan; Dai, Xiong-Kai

    2016-06-01

    This retrospective study recruited 150 patients with recurrent major depressive disorder (MDD) who received modified electroconvulsive therapy (MECT) and 150 cases treated with repetitive transcranial magnetic stimulation (rTMS), which aimed to compare the short- and long-term effectiveness, as well as economic outcomes, of MECT and rTMS with a large sample size in patients with recurrent MDD. The results showed that the response rate of patients in the rTMS group was lower than that in the MECT group (46.0% vs 58.7%, p < 0.05). Patients in the rTMS group had elevated rate of dizziness, but reduced rates of poor memory and headache, as well as lower costs compared with the MECT group (p < 0.05). Importantly, we found that the relapse-free survival of patients was similar between the rTMS and MECT groups in the long term. In conclusion, rTMS is an alternative method for MECT in the treatment of patients with recurrent MDD.

  10. 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.

  11. 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

  12. Don't Let Disability Derail Long-Term Financial Security: Enhancing Retirement Security in a DC World.

    PubMed

    Rappaport, Anna M

    2016-01-01

    Long-term disability (LTD) protection, such as a defined contribution (DC) disability supplement, is critical for good long-term security in a DC environment. For those with a strong LTD program already in place, this challenge can be addressed by providing a DC disability benefit that replaces DC contributions during periods of LTD. If there is no LTD program, that is needed first. Appropriate disability coverage is vital if the DC system truly is to deliver long-term retirement security. This article discusses issues in achieving such coverage and provides ideas to help in developing programs. Few such programs exist today, but it is hoped that this article will encourage more employers to adopt them.

  13. MHC class I immune proteins are critical for hippocampus-dependent memory and gate NMDAR-dependent hippocampal long-term depression.

    PubMed

    Nelson, P Austin; Sage, Jennifer R; Wood, Suzanne C; Davenport, Christopher M; Anagnostaras, Stephan G; Boulanger, Lisa M

    2013-09-01

    Memory impairment is a common feature of conditions that involve changes in inflammatory signaling in the brain, including traumatic brain injury, infection, neurodegenerative disorders, and normal aging. However, the causal importance of inflammatory mediators in cognitive impairments in these conditions remains unclear. Here we show that specific immune proteins, members of the major histocompatibility complex class I (MHC class I), are essential for normal hippocampus-dependent memory, and are specifically required for NMDAR-dependent forms of long-term depression (LTD) in the healthy adult hippocampus. In β2m(-/-)TAP(-/-)mice, which lack stable cell-surface expression of most MHC class I proteins, NMDAR-dependent LTD in area CA1 of adult hippocampus is abolished, while NMDAR-independent forms of potentiation, facilitation, and depression are unaffected. Altered NMDAR-dependent synaptic plasticity in the hippocampus of β2m(-/-)TAP(-/-)mice is accompanied by pervasive deficits in hippocampus-dependent memory, including contextual fear memory, object recognition memory, and social recognition memory. Thus normal MHC class I expression is essential for NMDAR-dependent hippocampal synaptic depression and hippocampus-dependent memory. These results suggest that changes in MHC class I expression could be an unexpected cause of disrupted synaptic plasticity and cognitive deficits in the aging, damaged, and diseased brain.

  14. Reduction mammaplasty improves levels of anxiety, depression and body image satisfaction in patients with symptomatic macromastia in the short and long term.

    PubMed

    Pérez-Panzano, Esther; Gascón-Catalán, Ana; Sousa-Domínguez, Ramón; Carrera-Lasfuentes, Patricia; García-Campayo, Javier; Güemes-Sánchez, Antonio

    2017-01-11

    To evaluate the psychological consequences (anxiety, depression and body image dissatisfaction) of symptomatic macromastia and the effectiveness of breast reduction surgery in re-establishing the mental health of the patient in the short and long term. 119 patients over 18 years old who had been diagnosed with symptomatic macromastia were assessed, before surgery, one month after the operation and one year later. Patients completed the Hospital Anxiety and Depression Scale (HADS) and the Body Image Dissatisfaction subscale of the Eating Disorders Inventory (EDI-2). Participants were also asked about their physical appearance, social relationships and their satisfaction with regards to clothing and dress. The average age of the patients was 40.7 (SD = 12.02), 80.2% had a body mass index ≥25 kg/m(2). Before surgery, we found psychological distress with values indicating clinical anxiety and body image dissatisfaction. Younger women (< 36 years old) were more psychologically affected. At one month after surgery, there were significant improvements: there were lower scores for anxiety (p < 0.001), depression (p < 0.001) and body image dissatisfaction (p < 0.001). When compared with the pre-surgery scores, all these results showed improvement one year after the intervention (p < 0.001). There were also improvements in social relationships (p < 0.001) and satisfaction with clothing and dress. Reduction mammaplasty can alleviate the psychological impact of symptomatic macromastia.

  15. The Effects of Lifestyle Interventions on (Long-Term) Weight Management, Cardiometabolic Risk and Depressive Symptoms in People with Psychotic Disorders: A Meta-Analysis

    PubMed Central

    Bruins, Jojanneke; Jörg, Frederike; Bruggeman, Richard; Slooff, Cees; Corpeleijn, Eva; Pijnenborg, Marieke

    2014-01-01

    Aims The aim of this study was to estimate the effects of lifestyle interventions on bodyweight and other cardiometabolic risk factors in people with psychotic disorders. Additionally, the long-term effects on body weight and the effects on depressive symptoms were examined. Material and Methods We searched four databases for randomized controlled trials (RCTs) that compared lifestyle interventions to control conditions in patients with psychotic disorders. Lifestyle interventions were aimed at weight loss or weight gain prevention, and the study outcomes included bodyweight or metabolic parameters. Results The search resulted in 25 RCTs -only 4 were considered high quality- showing an overall effect of lifestyle interventions on bodyweight (effect size (ES) = −0.63, p<0.0001). Lifestyle interventions were effective in both weight loss (ES = −0.52, p<0.0001) and weight-gain-prevention (ES = −0.84, p = 0.0002). There were significant long-term effects, two to six months post-intervention, for both weight-gain-prevention interventions (ES = −0.85, p = 0.0002) and weight loss studies (ES = −0.46, p = 0.02). Up to ten studies reported on cardiometabolic risk factors and showed that lifestyle interventions led to significant improvements in waist circumference, triglycerides, fasting glucose and insulin. No significant effects were found for blood pressure and cholesterol levels. Four studies reported on depressive symptoms and showed a significant effect (ES = −0.95, p = 0.05). Conclusion Lifestyle interventions are effective in treating and preventing obesity, and in reducing cardiometabolic risk factors. However, the quality of the studies leaves much to be desired. PMID:25474313

  16. Zinc enhances long-term potentiation through P2X receptor modulation in the hippocampal CA1 region

    PubMed Central

    Loyola, Sebastian; Moreira-Ramos, Sandra; Zeise, Marc L.; Kirkwood, Alfredo; Huidobro-Toro, J. Pablo; Morales, Bernardo

    2013-01-01

    Zn2+ is an essential ion that is stored in and co-released from glutamatergic synapses and it modulates neurotransmitter receptors involved in long-term potentiation (LTP). However, the mechanism(s) underlying Zn2+-induced modulation of LTP remain(s) unclear. As the purinergic P2X receptors are relevant targets for Zn2+ action, we have studied their role in LTP modulation by Zn2+ in the CA1 region of rat hippocampal slices. Induction of LTP in the presence of Zn2+ revealed a biphasic effect – 5–50 μm enhanced LTP induction, whereas 100–300 μm Zn2+ inhibited LTP. The involvement of a purinergic mechanism is supported by the fact that application of the P2X receptor antagonists 2′,3′-O-(2,4,6-trinitrophenyl) ATP (TNP-ATP) and periodate-oxidized ATP fully abolished the facilitatory effect of Zn2+. Notably, application of the P2X7 receptor-specific antagonist Brilliant Blue G did not modify the Zn2+-dependent facilitation of LTP. Exogenous ATP also produced a biphasic effect – 0.1–1 μm ATP facilitated LTP, whereas 5–10 μm inhibited LTP. The facilitatory effect of ATP was abolished by the application of TNP-ATP and was modified in the presence of 5 μm Zn2+, suggesting that P2X receptors are involved in LTP induction and that Zn2+ leads to an increase in the affinity of P2X receptors for ATP. The latter confirms our previous results from heterologous expression systems. Collectively, our results indicate that Zn2+ at low concentrations enhances LTP by modulating P2X receptors. Although it is not yet clear which purinergic receptor subtype(s) is responsible for these effects on LTP, the data presented here suggest that P2X4 but not P2X7 is involved. PMID:21324005

  17. 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

  18. Zinc enhances long-term potentiation through P2X receptor modulation in the hippocampal CA1 region.

    PubMed

    Lorca, Ramón A; Rozas, Carlos; Loyola, Sebastian; Moreira-Ramos, Sandra; Zeise, Marc L; Kirkwood, Alfredo; Huidobro-Toro, J Pablo; Morales, Bernardo

    2011-04-01

    Zn²(+) is an essential ion that is stored in and co-released from glutamatergic synapses and it modulates neurotransmitter receptors involved in long-term potentiation (LTP). However, the mechanism(s) underlying Zn²(+) -induced modulation of LTP remain(s) unclear. As the purinergic P2X receptors are relevant targets for Zn²(+) action, we have studied their role in LTP modulation by Zn²(+) in the CA1 region of rat hippocampal slices. Induction of LTP in the presence of Zn²(+) revealed a biphasic effect - 5-50 μm enhanced LTP induction, whereas 100-300 μm Zn²(+) inhibited LTP. The involvement of a purinergic mechanism is supported by the fact that application of the P2X receptor antagonists 2',3'-O-(2,4,6-trinitrophenyl) ATP (TNP-ATP) and periodate-oxidized ATP fully abolished the facilitatory effect of Zn²(+) . Notably, application of the P2X₇ receptor-specific antagonist Brilliant Blue G did not modify the Zn²(+) -dependent facilitation of LTP. Exogenous ATP also produced a biphasic effect - 0.1-1 μm ATP facilitated LTP, whereas 5-10 μm inhibited LTP. The facilitatory effect of ATP was abolished by the application of TNP-ATP and was modified in the presence of 5 μm Zn²(+) , suggesting that P2X receptors are involved in LTP induction and that Zn²(+) leads to an increase in the affinity of P2X receptors for ATP. The latter confirms our previous results from heterologous expression systems. Collectively, our results indicate that Zn²(+) at low concentrations enhances LTP by modulating P2X receptors. Although it is not yet clear which purinergic receptor subtype(s) is responsible for these effects on LTP, the data presented here suggest that P2X₄ but not P2X₇ is involved. © 2011 The Authors. European Journal of Neuroscience © 2011 Federation of European Neuroscience Societies and Blackwell Publishing Ltd.

  19. 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…

  20. 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…

  1. 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...

  2. 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...

  3. 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

  4. The impact of chronic mild stress on long-term depressive behavior in rats which have survived sepsis.

    PubMed

    Steckert, Amanda V; Dominguini, Diogo; Michels, Monique; Abelaira, Helena M; Tomaz, Débora B; Sonai, Beatriz; de Moura, Airam B; Matos, Danyela; da Silva, Júlia B I; Réus, Gislaine Z; Barichello, Tatiana; Quevedo, João; Dal-Pizzol, Felipe

    2017-11-01

    The present study was created to investigate the effects of chronic mild stress (CMS) on the depressive behavior and neurochemical parameters of rats that were subjected to sepsis. Wistar rats were subjected to a CMS protocol, and sepsis was induced by cecal ligation and perforation (CLP). The animals were then divided into 4 separate groups; Control + Sham (n = 20), Control + CLP (n = 30), CMS + Sham (n = 20) and CMS + CLP (n = 30). Body weight, food and water intake and mortality were measured on a daily basis for a period of 10 days after the induction of sepsis. Locomotor activity, splash and forced swimming tests were performed ten days after CLP. At the end of the test period, the animals were euthanized, and the prefrontal cortex and hippocampus were removed to determine the levels of cytokines and oxidative damage. Our results show that there was no significant interaction between CMS and CLP in relation to locomotor activity and the forced swimming test. However, we did observe a significant decrease in total grooming time in the Control + CLP and CMS + Sham groups, with the CMS + CLP group showing behavior similar to that of the control animals. This was found to be related to a decrease in the levels of brain cytokines, and not to oxidative damage parameters. Collectively, our results suggest that a previous stress caused by CMS can protect the brain against the systemic acute and severe stress elicited by sepsis. Copyright © 2017 Elsevier Ltd. All rights reserved.

  5. 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.…

  6. 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,…

  7. Expanding Retrieval Practice Promotes Short-Term Retention, but Equally Spaced Retrieval Enhances Long-Term Retention

    ERIC Educational Resources Information Center

    Karpicke, Jeffrey D.; Roediger, Henry L., III

    2007-01-01

    Expanding retrieval practice (T. K. Landauer & R. A. Bjork, 1978) is regarded as a superior technique for promoting long-term retention relative to equally spaced retrieval practice. In Experiments 1 and 2, the authors found that expanding retrieval practice of vocabulary word pairs produced short-term benefits 10 min after learning,…

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

    ERIC Ed