Early life stress leads to gene expression down-regulation in prefrontal cortex [RNA-seq]
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ABSTRACT:
ORGANISM(S): Rattus norvegicus
PROVIDER: GSE153043 | GEO | 2021/12/31
REPOSITORIES: GEO
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Project description:Early life stress (ELS) is associated with adverse mental health outcomes including anxiety, depression and addiction-like behaviours. While ELS is known to affect the developing brain by leading to increased stress responsiveness and increased glucocorticoid levels, the molecular mechanisms underlying the detrimental effects of ELS remain incompletely characterised. Rodent models have been instrumental in beginning to uncover the molecular and cellular underpinnings of ELS. Limited nesting (LN), an ELS behavioural paradigm with significant improvements over maternal separation, mimics human maternal neglect. We have previously shown that LN leads to anxiety like-behaviours in rats. Here we assessed gene expression changes induced by ELS in rat prefrontal cortex by RNA-sequencing. We show that LN leads primarily to transcriptional repression and identify a molecular signature of LN in rat PFC that is robust to the behavioural paradigm and replicable across rodent species (mouse and rat).
2021-12-31 | GSE153042 | GEO
Project description:prenatal stress response, genetic modification Background: Prenatal stress (PS) exposure has been shown to increase the risk for emotional disorders in later life. Furthermore, the serotonin transporter (5-HTT) genotype is suggested to exert a modulating effect on the association between early life stress and the risk for depression. In the present study, we use a 5-HTT x PS paradigm to investigate whether the effects of PS are dependent upon the 5-HTT genotype. Methods: The effects of PS on cognition, anxiety- and depression-related behaviour were examined using a maternal restraint stress paradigm of PS in C57BL6 wild-type (WT) and heterozygous (+/-) 5-HTT knockout mice. Additionally, in the female offspring, a genome-wide hippocampal gene expression screening was performed. Results: 5-HTT +/- offspring showed enhanced memory performance and signs of reduced anxiety as compared to WT offspring. Conversely, exposure of 5-HTT +/- mice to PS was associated with altered stress-responsivity and increased depressive-like behaviour, particularly in female offspring. Further, 5-HTT genotype, PS and their interaction differentially affected the expression of numerous genes and related pathways within the female hippocampus. Specifically, MAPK and neurotrophin signalling were regulated by both the 5-HTT +/- genotype and PS exposure, whereas cytokine and Wnt signalling were affected in a 5-HTT genotype x PS manner, indicating a gene x environment interaction at the molecular level. Conclusions: The long-term behavioural effects of PS in C57BL6 mice are partly dependent on the 5-HTT genotype. Further, hippocampal gene expression profiles suggest that distinct molecular mechanisms mediate the behavioural effects of the 5-HTT genotype, PS exposure, and their interaction. total samples analysed are 12
2011-12-12 | E-GEOD-26025 | biostudies-arrayexpress
Project description:We used a mouse maternal separation model, a well-known paradigm of early adversity, to test the hypothesis that transcriptional changes in peripheral blood mononuclear cells (PBMCs) are paralleled by specific gene expression changes in three brain regions that are involved in the stress response. Furthermore, we evaluated whether gene expression profiles of PBMCs could be used to predict stress-related animal behaviours.
2009-07-31 | E-MEXP-2101 | biostudies-arrayexpress
Project description:prenatal stress response, genetic modification Background: Prenatal stress (PS) exposure has been shown to increase the risk for emotional disorders in later life. Furthermore, the serotonin transporter (5-HTT) genotype is suggested to exert a modulating effect on the association between early life stress and the risk for depression. In the present study, we use a 5-HTT x PS paradigm to investigate whether the effects of PS are dependent upon the 5-HTT genotype. Methods: The effects of PS on cognition, anxiety- and depression-related behaviour were examined using a maternal restraint stress paradigm of PS in C57BL6 wild-type (WT) and heterozygous (+/-) 5-HTT knockout mice. Additionally, in the female offspring, a genome-wide hippocampal gene expression screening was performed. Results: 5-HTT +/- offspring showed enhanced memory performance and signs of reduced anxiety as compared to WT offspring. Conversely, exposure of 5-HTT +/- mice to PS was associated with altered stress-responsivity and increased depressive-like behaviour, particularly in female offspring. Further, 5-HTT genotype, PS and their interaction differentially affected the expression of numerous genes and related pathways within the female hippocampus. Specifically, MAPK and neurotrophin signalling were regulated by both the 5-HTT +/- genotype and PS exposure, whereas cytokine and Wnt signalling were affected in a 5-HTT genotype x PS manner, indicating a gene x environment interaction at the molecular level. Conclusions: The long-term behavioural effects of PS in C57BL6 mice are partly dependent on the 5-HTT genotype. Further, hippocampal gene expression profiles suggest that distinct molecular mechanisms mediate the behavioural effects of the 5-HTT genotype, PS exposure, and their interaction.
2011-12-12 | GSE26025 | GEO
Project description:Early life stress (ELS), such as neglect and maltreatment, exhibits a strong impact on the mental and brain development of children. However, it is not fully understood how ELS affects the function in developing prefrontal cortex (PFC). In this study, we performed social isolation on weaned pre-adolescent mice and investigated how ELS could affect the function in behavior and transcriptome in PFC. We found that reductions of social interaction, social preference, and social novelty in ELS mice. Moreover, an increase of anxiety-like behavior was observed in ELS mice, but there were no changes in weight and repetitive behavior. To identify the gene involved in social behavior, we conducted transcriptome analysis and identified 15 differentially expressed genes (DEGs) in the PFC of ELS mice. These genes were involved in transcriptional regulation, stress, and synaptic signaling. We also found that a decreased number of neurons and an increased number of microglia in the PFC of ELS mice. These results suggest that ELS affects PFC cytoarchitecture by stress signal transduction and eventually alters mouse behavior. Our study demonstrates that ELS influences behavior, transcriptome and cytoarchitecture in the brain of adolescent mice.
2021-11-30 | GSE180055 | GEO
Project description:Depression is a heterogeneous disorder characterized by a wide range of symptoms, including but not restricted to increased anxiety-like behavior, altered stress responsivity, increased depressive like behavior, decreased pleasure seeking, and altered susceptibility to drugs of abuse. Adding another level of complexity to the disease is the fact that individuals differ in their susceptibility to depression. Research done over the past decade has highlighted the contribution of early life adverse experience to this individual differences in vulnerability to depression. Such studies have been done at the clinical as well as the preclinical level, where rodent and primate models of adverse postnatal environment such as Maternal Separation (MS) are used. MS involves separation of the pup from the dam for 3h every day for the first two weeks of postnatal life. The MS model has been characterized to produce long lasting anxiety-like behavior, depressive behavior and altered stress responsivity in adulthood. While several molecular mechanisms have been hypothesized to mediate the long lasting effects of MS, the serotonin 2a receptor is an attractive candidate, given its role in regulating anxiety-like behavior. So we set out to ask if Maternal Separation alters the 5HT2a responses. In order to assay if MS alters the transcriptional targets of the 5Ht2a receptor, we use a drug that stimulates the 5Ht2a receptor, DOI. The experiment involves injecting both control and MS animals with DOI and looking at the transcriptome induced by DOI under control and MS conditions. This would help understand how the adverse early life experience MS, alters the transcriptional response of an adult rat to stimulation at the 5HT2a receptor, which is physiologically seen in conditions of stress. Maternal Separation (MS) was carried out according to standard protocol. Briefly, upon birth the litters were assigned to either the control or the maternal separation group. Pups from the maternal separation litters were separated from their mother every day for a period of 3 hours from postnatal day 2 (p2) to postnatal day 14 (p14) while the control litters were left undisturbed. After p14, the maternally separated pups were left undisturbed and all litters were weaned at postnatal day 30. Experiments on adult control and MS rats were performed at postnatal day 60. We wanted to ask if a history of adverse experience in early life like MS would alter the transcriptional response of the adult rat to the 5Ht2a agonist DOI. In order to measure the transcriptional changes induced by DOI in control and maternally separated animals, 15 rats (7 - Control and 8 - Maternally Separated) were injected i.p. with either saline or 8 mg/kg DOI. The groups included Control (Control rats injected with saline; n=3), DOI (control rats injected with 8 mg/kg DOI; n=4), MS (MS rats injected with saline, n=4) and MS+ DOI (MS rats injected with 8 mg/kg DOI, n=4). Rats were sacrificed 2 hours after the injection by decapitation. The prefrontal cortex was quickly dissected out and stored at -70 till further use. Total RNA from each rat was extracted, labeled with Cy3 and hybridized onto Agilent Custom Rat Array 8X15K (AMADID: G2509F_16352). Each biological replicate was hybridized onto one array making the total number of arrays 15.
2013-04-01 | E-GEOD-23728 | biostudies-arrayexpress
Project description:Diabetes is one of the major risk factors for Alzheimer’s disease (AD) development. The role of elevated levels of glucose, methylglyoxal (MGO), and advanced glycation end products (AGEs) in diabetes in the pathogenesis of the AD is not well understood. In this pursuit, we studied the role of methylglyoxal in the pathogenesis of AD in rat models. The elevated plus-maze (EPM) behavioural study indicated that MGO induces anxiety. Treatment of telmisartan (RAGE expression inhibitor) and aminoguanidine (MGO quencher) attenuated MGO induced anxiety. Further, hippocampal proteomics demonstrated that MGO treated rats differentially regulate proteins involved in calcium homeostasis, mitochondrial functioning, and apoptosis which may affect neurotransmission and neuronal plasticity. Hippocampal tau phosphorylation level was increased in MGO treated rats which was reduced in presence in aminoguanidine and telmisartan. Plasma fructosamine level was increased upon MGO treatment. Hippocampal histochemistry showed vascular degeneration and neuronal loss upon MGO treatment. This study provides mechanistic insight into the role of MGO in the diabetes-associated development of AD.
2024-01-26 | PXD037673 | Pride
Project description:We examined effects of early life stress (ELS) and environmental enrichment (EE) during development on BACHD rat striatal gene expression using RNA sequencing
2018-04-13 | GSE107259 | GEO
Project description:Depression is a heterogeneous disorder characterized by a wide range of symptoms, including but not restricted to increased anxiety-like behavior, altered stress responsivity, increased depressive like behavior, decreased pleasure seeking, and altered susceptibility to drugs of abuse. Adding another level of complexity to the disease is the fact that individuals differ in their susceptibility to depression. Research done over the past decade has highlighted the contribution of early life adverse experience to this individual differences in vulnerability to depression. Such studies have been done at the clinical as well as the preclinical level, where rodent and primate models of adverse postnatal environment such as Maternal Separation (MS) are used. MS involves separation of the pup from the dam for 3h every day for the first two weeks of postnatal life. The MS model has been characterized to produce long lasting anxiety-like behavior, depressive behavior and altered stress responsivity in adulthood. While several molecular mechanisms have been hypothesized to mediate the long lasting effects of MS, the serotonin 2a receptor is an attractive candidate, given its role in regulating anxiety-like behavior. So we set out to ask if Maternal Separation alters the 5HT2a responses. In order to assay if MS alters the transcriptional targets of the 5Ht2a receptor, we use a drug that stimulates the 5Ht2a receptor, DOI. The experiment involves injecting both control and MS animals with DOI and looking at the transcriptome induced by DOI under control and MS conditions. This would help understand how the adverse early life experience MS, alters the transcriptional response of an adult rat to stimulation at the 5HT2a receptor, which is physiologically seen in conditions of stress.
2013-04-01 | GSE23728 | GEO
Project description:Despite studies providing insight into the neurobiology of chronic stress, depression and anxiety, long noncoding RNA (lncRNA)-mediated mechanisms underlying the common and distinct pathophysiology of these stress-induced disorders remain nonconclusive. In a previous study, we used the chronic mild stress paradigm to separate depression-susceptible, anxiety-susceptible and insusceptible rat subpopulations. In the current study, lncRNA and messenger RNA (mRNA) expression was comparatively profiled in the hippocampus of the three stress groups using microarray technology. Groupwise comparisons identified distinct sets of lncRNAs and mRNAs associated with the three different behavioral phenotypes of the stressed rats. To investigate the regulatory roles of the dysregulated lncRNAs upon mRNA expression, correlations between the differential lncRNAs and mRNAs were first analyzed by combined use of weighted gene coexpression network analysis and ceRNA theory-based methods. Subsequent functional analysis of strongly correlated mRNAs indicated that the dysregulated lncRNAs were involved in various biological pathways and processes to specifically induce rat susceptibility or resiliency to depression or anxiety. Further intersectional analysis of phenotype-associated and drug-associated lncRNA-mRNA networks and subnetworks assisted in identifying 16 hub lncRNAs as potential targets of anti-depression/anxiety drugs. Collectively, our study established the molecular basis for understanding the similarities and differences in pathophysiological mechanisms underlying stress-induced depression or anxiety and stress resiliency, revealing several important lncRNAs that represent potentially new therapeutic drug targets for depression and anxiety disorders.
2020-08-21 | GSE156580 | GEO