The role of NCAM in auditory fear conditioning and its modulation by stress: a focus on the amygdala

n/

Adult hippocampal neuroplasticity triggers susceptibility to recurrent depression

Depression is a highly prevalent and recurrent neuropsychiatric disorder associated with alterations in emotional and cognitive domains. Neuroplastic phenomena are increasingly considered central to the etiopathogenesis of and recovery from depression. Nevertheless, a high number of remitted patients experience recurrent episodes of depression, remaining unclear how previous episodes impact on behavior and neuroplasticity and/or whether modulation of neuroplasticity is important to prevent recurrent depression. Through re-exposure to an unpredictable chronic mild stress protocol in rats, we observed the re-appearance of emotional and cognitive deficits. Furthermore, treatment with the antidepressants fluoxetine and imipramine was effective to promote sustained reversion of a depressive-like phenotype; however, their differential impact on adult hippocampal neuroplasticity triggered a distinct response to stress re-exposure: while imipramine re-established hippocampal neurogenesis and neuronal dendritic arborization contributing to resilience to recurrent depressive-like behavior, stress re-exposure in fluoxetine-treated animals resulted in an overproduction of adult-born neurons along with neuronal atrophy of granule neurons, accounting for an increased susceptibility to recurrent behavioral changes typical of depression. Strikingly, cell proliferation arrest compromised the behavior resilience induced by imipramine and buffered the susceptibility to recurrent behavioral changes promoted by fluoxetine. This study shows that previous exposure to a depressive-like episode impacts on the behavioral and neuroanatomical changes triggered by subsequent re-exposure to similar experimental conditions and reveals that the proper control of adult hippocampal neuroplasticity triggered by antidepressants is essential to counteract recurrent depressive-like episodes.FCT (IF/01079/2014). This article has been developed under the scope of the project NORTE-01-0145-FEDER-000013, supported by the Northern Portugal Regional Operational Programme (NORTE 2020), under the Portugal 2020 Partnership Agreement, through the European Regional Development Fund (FEDER). This work has been funded by FEDER funds, through the Competitiveness Factors Operational Programme (COMPETE), and by National funds, through the FCT, under the scope of the project POCI-01-0145-FEDER-007038info:eu-repo/semantics/publishedVersio

Impact of chronic stress protocols in learning and memory in rodents: systematic review and meta-analysis

The idea that maladaptive stress impairs cognitive function has been a cornerstone of decades in basic and clinical research. However, disparate findings have reinforced the need to aggregate results from multiple sources in order to confirm the validity of such statement. In this work, a systematic review and meta-analyses were performed to aggregate results from rodent studies investigating the impact of chronic stress on learning and memory. Results obtained from the included studies revealed a significant effect of stress on global cognitive performance. In addition, stressed rodents presented worse consolidation of learned memories, although no significantly differences between groups at the acquisition phase were found. Despite the methodological heterogeneity across studies, these effects were independent of the type of stress, animals' strains or age. However, our findings suggest that stress yields a more detrimental effect on spatial navigation tests' performance. Surprisingly, the vast majority of the selected studies in this field did not report appropriate statistics and were excluded from the quantitative analysis. We have therefore purposed a set of guidelines termed PROBE (Preferred Reporting Orientations for Behavioral Experiments) to promote an adequate reporting of behavioral experiments.This work was funded by the European Commission (FP7) "SwitchBox" (Contract HEALTH-F2-2010-259772) project and co-financed by the Portuguese North Regional Operational Program (ON.2 - O Novo Norte) under the National Strategic Reference Framework (QREN), through the European Regional Development Fund (FEDER), and by Fundacao Calouste Gulbenkian (Portugal) (Contract grant number: P-139977; project "Better mental health during ageing based on temporal prediction of individual brain ageing trajectories (TEMPO)"). PSM is supported by an FCT fellowship grant, from the PhD-iHES program, with the reference PDE/BDE/113601/2015.info:eu-repo/semantics/publishedVersio

The bed nucleus of stria terminalis and the amygdala as targets of antenatal glucocorticoids: implications for fear and anxiety responses

Rationale: Several human and experimental studies have shown that early life adverse events can shape physical and mental health in adulthood. Stress or elevated levels of glucocorticoids (GCs) during critical periods of development seem to contribute for the appearance of neurospyschiatric conditions such as anxiety and depression, albeit the underlying mechanisms remain to be fully elucidated. Objectives: The aim of the present study was to determine the long-term effect of prenatal erxposure to dexamethasone- DEX (synthetic GC widely used in clinics) in fear and anxious behavior and identify the neurochemical, morphological and molecular correlates. Results: Prenatal exposure to DEX triggers a hyperanxious phenotype and altered fear behavior in adulthood. These behavioral traits were correlated with increased volume of the bed nucleus of the stria terminalis (BNST), particularly the anteromedial subivision which presented increased dendritic length; in parallel, we found an increased expression of synapsin and NCAM in the BNST of these animals. Remarkably, DEX effects were opposite in the amygdala, as this region presented reduced volume due to significant dendritic atrophy. Albeit no differences were found in dopamine and its metabolite levels in the BNST, this neurotransmitter was substantially reduced in the amygdala, which also presented an up-regulation of dopamine receptor 2. Conclusions: Altogether our results show that in utero DEX exposure can modulate anxiety and fear behavior in parallel with significant morphological, neurochemical and molecular changes; importantly, GCs seem to differentially affect distinct brain regions involved in this type of behaviors.This study was supported by a grant from the Institute for the Study of Affective Neuroscience (ISAN). AJR is supported by a Fundação para a Ciência e Tecnologia (FCT) grant

Facilitation of AMPA Receptor Synaptic Delivery as a Molecular Mechanism for Cognitive Enhancement

A small peptide from a neuronal cell adhesion molecule enhances synaptic plasticity in the hippocampus and results in improved cognitive performance in rats