Repeated exposure with short-term behavioral stress resolves pre-existing stress-induced depressive-like behavior in mice
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PROVIDER: PRJNA761420 | ENA |
REPOSITORIES: ENA
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Project description:Chronic stress induces adaptive changes in the brain via the cumulative action of glucocorticoids, which is associated with mood disorders. Here we show that repeated daily five-minute restraint resolves pre-existing stress-induced depressive-like behavior in mice. Repeated injection of glucocorticoids in low doses mimics the anti-depressive effects of short-term stress. Repeated exposure to short-term stress and injection of glucocorticoids activate neurons in largely overlapping regions of the brain, as shown by c-Fos staining, and reverse distinct stress-induced gene expression profiles. Chemogenetic inhibition of neurons in the prelimbic cortex projecting to the nucleus accumbens, basolateral amygdala, or bed nucleus of the stria terminalis results in anti-depressive effects similarly to short-term stress exposure, while only inhibition of neurons in the prelimbic cortex projecting to the bed nucleus of the stria terminalis rescues glucocorticoid release. In summary, we show that short-term stress can reverse adaptively altered stress gains and resolve stress-induced depressive-like behavior.
2021-09-09 | GSE183624 | GEO
Project description:Chronic stress induces adaptive changes in the brain via the cumulative action of glucocorticoids, which is associated with mood disorders. Here we show that repeated daily five-minute restraint resolves pre-existing stress-induced depressive-like behavior in mice. Repeated injection of glucocorticoids in low doses mimics the anti-depressive effects of short-term stress. Repeated exposure to short-term stress and injection of glucocorticoids activate neurons in largely overlapping regions of the brain, as shown by c-Fos staining, and reverse distinct stress-induced gene expression profiles. Chemogenetic inhibition of neurons in the prelimbic cortex projecting to the nucleus accumbens, basolateral amygdala, or bed nucleus of the stria terminalis results in anti-depressive effects similarly to short-term stress exposure, while only inhibition of neurons in the prelimbic cortex projecting to the bed nucleus of the stria terminalis rescues defective glucocorticoid release. In summary, we show that short-term stress can reverse adaptively altered stress gains and resolve stress-induced depressive-like behavior.
| S-EPMC8602389 | biostudies-literature
Project description:We demonstrated that the offspring of depressed fathers display reduced resilience to stress and enhanced susceptibility to depression. To explain the observed behavioural phenotypes of depression in offspring produced by depressed fathers, molecular profiling was performed in key brain regions.We examined the hippocampal sample from normal male mice, stress induced depressive male mice and male offspring born to stress-induced depressed male mice by RNA sequencing.
2020-06-28 | GSE133494 | GEO
Project description:Stressful life events increase risk for depression, yet the molecular mechanisms by which stress is encoded in the brain to induce maladaptive behaviors are not well understood. Emerging evidence has shown that stress dysregulates gene expression in the brain, yet the cellular origin of these gene expression alterations has yet to be determined. To address this question, we used a chronic unpredictable stress (CUS) paradigm that drives depressive- and anxiety-like behaviors in male and female mice and single-nucleus transcriptomics to identify cell type-specific gene expression changes in the cortex. We find that neocortical excitatory neurons are particularly vulnerable to chronic stress exposure, and that CUS reprograms these cells to decrease transcription of synaptic genes involved in glutamatergic neurotransmission. We identify the ubiquitously expressed factor, Yin Yang 1 (YY1), as a key driver of the transcriptional reprogramming observed in excitatory neurons isolated from CUS mice. Selective depletion of YY1 in excitatory neurons of the prefrontal cortex (PFC) increases the stress sensitivity of mice, inducing depressive- and anxiety-related behaviors following an abbreviated stress exposure and deregulating expression of key stress-related genes in the PFC. Importantly, we find that YY1 functions in both males and females to facilitate stress coping. This work establishes a novel mechanism underlying chronic stress-induced behavior, in which epigenetic responses to stress in PFC excitatory neurons are mediated by stress-dependent YY1 activity. Our findings demonstrate how post-mitotic neurons adapt to stress experience and identify a novel molecular target that is generalizable to males and females for therapeutic treatment of stress-related neuropsychiatric disorders.
2021-11-19 | GSE145970 | GEO
Project description:Genome-wide MeDIP-Sequencing was carried out on a total of 50 monozygotic twin pairs from the UK and Australia that are discordant for depression. We show that major depressive disorder is associated with significant hypermethylation within the coding region of ZBTB20, and is replicated in an independent cohort of 356 unrelated case-control individuals. The twins with major depressive disorder also show increased global variation in methylation in comparison with their unaffected co-twins. ZBTB20 plays an essential role in the specification of the Cornu Ammonis-1 field identity in the developing hippocampus, a region previously implicated in the development of major depressive disorder. Epigenetic study of MZ twins discordant for Major Depressive Disorder
2014-01-21 | E-GEOD-54222 | biostudies-arrayexpress
Project description:Human major depressive disorder (MDD), along with related mood disorders, is among the world’s greatest public health concerns, however, its pathophysiology remains poorly understood. Persistent changes in gene expression are known to promote physiological aberrations implicated in MDD. More recently, histone mechanisms affecting cell-type and regional specific chromatin structures have also been shown to contribute to transcriptional programs related to depressive behaviors, as well as responses to antidepressants (ADs). Although much emphasis has been placed in recent years on roles for histone posttranslational modifications (PTMs) and chromatin remodeling events in the etiology of MDD, it has become increasingly clear that replication-independent histone variants (e.g., H3.3), which differ in primary amino acid sequence from their canonical counterparts, similarly play critical roles in the regulation of activity-dependent neuronal transcription, synaptic connectivity and behavioral plasticity. Here, we demonstrate a novel role for increased H3.3 dynamics in nucleus accumbens (NAc)––a key limbic brain reward region––in the regulation of aberrant social stress-mediated gene expression, abnormal dendritic morphology and the precipitation of depressive-like behaviors in mice. We find that molecular blockade of these dynamics promotes resilience to chronic social stress and results in a partial re-normalization of stress-associated transcriptional patterns in NAc. In sum, our findings establish H3.3 dynamics as a critical, and previously undocumented, regulator of mood, and suggest that future therapies aimed at modulating striatal histone dynamics may potentiate beneficial behavioral adaptations to negative emotional stimuli.
2017-02-08 | GSE85900 | GEO
Project description:Genome-wide MeDIP-Sequencing of 23 monozygotic twin pairs (n=46) from Australia discordant for major depressive disorder (MDD). MeDIP-seq of 23 monozygotic twin pairs discordant for major depressive disorder. MZ twin pairs were compared to identify significantly differently methylated sites associated with MDD.
2014-01-25 | E-GEOD-54370 | biostudies-arrayexpress
Project description:Despite depression being one of the most prevalent and debilitating disorders worldwide, it has been difficult to understand its pathophysiology and to develop more effective treatments. Maladaptive transcriptional regulation within limbic neural circuits, including reward processing regions such as the nucleus accumbens (NAc), in response to chronic stress is thought to be a major contributor to the development of the syndrome. Epigenetic events?in particular, histone writers and erasers?that alter chromatin structure to regulate programs of gene expression have increasingly been associated with depression-related behavioral abnormalities in animal models and in depressed humans examined postmortem. However, very little is known about the ATP-dependent chromatin remodelers that control nucleosome positioning and the packing state of chromatin. Here we show that the ACF complex, part of the ISWI family of chromatin remodelers, is persistently and selectively upregulated in the NAc of mice that are susceptible to chronic social stress, as well as in the NAc of depressed human. We further establish that ACF induction is both necessary and sufficient for susceptibility to stress-induced depressive-like behaviors. Using ChIP-seq, we demonstrate that altered ACF binding after chronic stress is strongly correlated with altered nucleosome positioning, in particular, around the transcriptional start sites of affected genes. These alterations in ACF binding and nucleosome repositioning are associated with repressed expression of a subset of genes in animals that are susceptible to chronic stress. Together, these findings establish that active ATP-dependent chromatin remodeling by the ACF complex is a key regulator in the repression of genes that mediate susceptibility to social stress, and provide novel candidate targets for improved therapeutics of depression and other stress-related disorders. c57bl/6 mice underwent chronic social defeat stress (CSDS), and social interaction test was used to separate animals into control, susceptible and resilient groups. Nucleus accumbens (NAc) tissue was collected 48 hours after the last defeat session, and then Acf1, SNF2H ChIP-seq or H3 MNase-seq were performed based on the control, susceptible, and resilient groups. Three sequencing replicates were performed on each group.
2015-09-21 | E-GEOD-54263 | biostudies-arrayexpress
Project description:Identify blood proteins relevant to paroxetine response in patients with major depressive disorder (MDD)
2022-05-20 | PXD028947 | Pride
Project description:Cytidine deaminase resolves replicative stress and protects pancreatic cancer from DNA-targeting drugs
| PRJNA1061149 | ENA