Transcriptome Alterations in ASMT Knockout-Induced Depression-Like Behaviors and Exercise Effects
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ABSTRACT:
PROVIDER: PRJNA812598 | ENA |
REPOSITORIES: ENA
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Project description:Sleep disorder caused by abnormal circadian rhythm is one of the main symptoms and risk factors of depression. N-acetylserotonin methyltransferase (ASMT), the last rate-limiting enzyme of melatonin (MT, a known hormone regulating circadian rhythms), has been reportedly associated with depression. Exercise can regulate circadian rhythm and play an important role in depression treatment. Recently, gene chip has been widely used in depression research. In the present study, we showed that ASMT knockout induced depression-like behaviors, which were ameliorated by swimming exercise. Moreover, swimming exercise increased serum levels of MT and 5-HT in ASMT knockout mice. In addition, transcriptome analysis identified 10 differentially expressed genes (DEGs) in KO mice compared with WT mice, and 29 DEGs in KO mice after swimming exercise. Among the DEGs, the direction and magnitude of change in Eps8l1 and Plcb2 were confirmed by qRT-PCR partly. Subsequent bioinformatic analysis showed that p53 signaling pathway, long-term depression and estrogen signaling pathway were enriched significantly. In the protein-protein interaction (PPI) networks, Mpp1 and Pidd1 were hub genes. These findings may provide new targets for the treatment of circadian rhythm-associated depression.
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2024-02-07 | PXD044453 | Pride
Project description:Sleep disorder caused by abnormal circadian rhythm is one of the main symptoms and risk factors of depression. As a known hormone regulating circadian rhythms, melatonin (MT) is also namely N-acetyl-5-methoxytryptamine. N-acetylserotonin methyltransferase (Asmt) is the key rate-limiting enzyme of MT synthesis and has been reportedly associated with depression. Although 50-90% of patients with depression have sleep disorders, there are no effective treatment ways in the clinic. Exercise can regulate circadian rhythm and play an important role in depression treatment. In the present study, we showed that Asmt knockout induced depression-like behaviors, which were ameliorated by swimming exercise. Moreover, swimming exercise increased serum levels of MT and 5-hydroxytryptamine (5-HT) in Asmt knockout mice. In addition, the microarray data identified 10 differentially expressed genes (DEGs) in KO mice compared with WT mice and 29 DEGs in KO mice after swimming exercise. Among the DEGs, the direction and magnitude of change in epidermal growth factor receptor pathway substrate 8-like 1 (Eps8l1) and phospholipase C-β 2 (Plcb2) were confirmed by qRT-PCR partly. Subsequent bioinformatic analysis showed that these DEGs were enriched significantly in the p53 signaling pathway, long-term depression and estrogen signaling pathway. In the protein-protein interaction (PPI) networks, membrane palmitoylated protein 1 (Mpp1) and p53-induced death domain protein 1 (Pidd1) were hub genes to participate in the pathological mechanisms of depression and exercise intervention. These findings may provide new targets for the treatment of depression.
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Project description:Emerging evidence has shown that noncoding RNAs, particularly microRNAs (miRNAs), contribute to the pathogenesis of mood and anxiety disorders, although the molecular mechanisms are poorly understood. Here we show altered levels of miR-17-92 in adult hippocampal neural progenitors have a significant impact in neurogenesis and anxiety- and depression-related behaviors in mice. miR-17-92 deletion in adult neural progenitors causes a decrease, while its overexpression an increase of neurogenesis in the dentate gyrus, through regulating genes in the glucocorticoid pathway, especially serum- and glucocorticoid-inducible protein kinase-1 (Sgk1). miR-17-92 knockout mice show anxiety- and depression-like behaviors, whereas miR-17-92 overexpressing mice exhibit anxiolytic and antidepression-like behaviors. Furthermore, we show that miR-17-92 expression in the adult mouse hippocampus responds to chronic stress, and miR-17-92 rescues proliferation defects, induced by corticosterone, in hippocampal neural progenitors. Our study uncovers a crucial role for miR-17-92 in adult neural progenitors to regulate neurogenesis and anxiety- and depression-like behaviors.
2016-12-09 | GSE83636 | GEO
Project description:Background: The schizophrenia associated gene, BRD1, encodes an epigenetic regulator which chromatin interactome is enriched with genes implicated in mental health. Alterations in histone modifications and epigenetic regulation contribute to brain transcriptomic changes in affective disorders and preclinical data supports a role for BRD1 in psychopathology. However, the implications of BRD1 on affective pathology remains poorly understood. Methods: We assessed affective behaviors and associated neurobiology in Brd1+/- mice along with their responses to Fluoxetine and Imipramine. This involves behavioral, neurostructural, and neurochemical characterizations along with regional cerebral gene expression profiling combined with integrative functional genomic analyses. Results: Here we report behavioral changes in female Brd1+/- mice with translational value to depressive symptomatology that can be alleviated by administration of antidepressant medications. Behavioral changes are accompanied by altered brain morphometry and imbalances in monoaminergic systems. In accordance, gene expression changes across brain tissues reveal altered neurotransmitter signaling and cluster in functional pathways associated with depression including ‘Adrenergic-, GPCR-, cAMP-, and CREB/CREM-signaling’. Integrative gene expression analysis specifically links changes in amygdaloid intracellular signaling activity to the behavioral treatment response in Brd1+/- mice. Conclusions: Collectively, our study highlights the importance of BRD1 as a modulator of affective pathology and adds to our understanding of the molecular mechanisms underlying affective disorders and their treatment response.
2020-06-20 | GSE150431 | GEO
Project description:Background: The schizophrenia associated gene, BRD1, encodes an epigenetic regulator which chromatin interactome is enriched with genes implicated in mental health. Alterations in histone modifications and epigenetic regulation contribute to brain transcriptomic changes in affective disorders and preclinical data supports a role for BRD1 in psychopathology. However, the implications of BRD1 on affective pathology remains poorly understood. Methods: We assessed affective behaviors and associated neurobiology in Brd1+/- mice along with their responses to Fluoxetine and Imipramine. This involves behavioral, neurostructural, and neurochemical characterizations along with regional cerebral gene expression profiling combined with integrative functional genomic analyses. Results: Here we report behavioral changes in female Brd1+/- mice with translational value to depressive symptomatology that can be alleviated by administration of antidepressant medications. Behavioral changes are accompanied by altered brain morphometry and imbalances in monoaminergic systems. In accordance, gene expression changes across brain tissues reveal altered neurotransmitter signaling and cluster in functional pathways associated with depression including ‘Adrenergic-, GPCR-, cAMP-, and CREB/CREM-signaling’. Integrative gene expression analysis specifically links changes in amygdaloid intracellular signaling activity to the behavioral treatment response in Brd1+/- mice. Conclusions: Collectively, our study highlights the importance of BRD1 as a modulator of affective pathology and adds to our understanding of the molecular mechanisms underlying affective disorders and their treatment response.
2020-06-20 | GSE150028 | GEO
Project description:The genomic causes of inbreeding depression are poorly known. Several studies have found widespread transcriptomic alterations in inbred organisms, but it remains unclear which of these alterations are causes of the depression and which are mere responses to the ensuing physiological stress. We made a c-DNA microarray analysis in Drosophila melanogaster attempting to differentiate causes from responses of inbreeding depression. The rationale of the experiment was that, while depression is a general phenomenon producing similar consequences in different inbred lines, its first genetic causes would be different for each inbred line, as they are expected to be caused by the fixation of rare deleterious genes. Many changes in expression were common to all sets, but fourteen genes, grouped in four expression clusters, showed strong set-specific changes, and were therefore candidates to be sources of the inbreeding depression observed. We took four sets of inbred sublines, each set descending from a different founding pair obtained from a large outbred stock, and compared the expression of the three most depressed sublines and the three least depressed sublines from each set.
2013-05-31 | E-GEOD-47176 | biostudies-arrayexpress
Project description:The genomic causes of inbreeding depression are poorly known. Several studies have found widespread transcriptomic alterations in inbred organisms, but it remains unclear which of these alterations are causes of the depression and which are mere responses to the ensuing physiological stress. We made a c-DNA microarray analysis in Drosophila melanogaster attempting to differentiate causes from responses of inbreeding depression. The rationale of the experiment was that, while depression is a general phenomenon producing similar consequences in different inbred lines, its first genetic causes would be different for each inbred line, as they are expected to be caused by the fixation of rare deleterious genes. Many changes in expression were common to all sets, but fourteen genes, grouped in four expression clusters, showed strong set-specific changes, and were therefore candidates to be sources of the inbreeding depression observed.
2013-05-31 | GSE47176 | GEO
Project description:Background: The schizophrenia associated gene, BRD1, encodes an epigenetic regulator which chromatin interactome is enriched with genes implicated in mental health. Alterations in histone modifications and epigenetic regulation contribute to brain transcriptomic changes in affective disorders and preclinical data supports a role for BRD1 in psychopathology. However, the implications of BRD1 on affective pathology remains poorly understood. Methods: We assessed affective behaviors and associated neurobiology in Brd1+/- mice along with their responses to Fluoxetine and Imipramine. This involves behavioral, neurostructural, and neurochemical characterizations along with regional cerebral gene expression profiling combined with integrative functional genomic analyses. Results: Here we report behavioral changes in female Brd1+/- mice with translational value to depressive symptomatology that can be alleviated by administration of antidepressant medications. Behavioral changes are accompanied by altered brain morphometry and imbalances in monoaminergic systems. In accordance, gene expression changes across brain tissues reveal altered neurotransmitter signaling and cluster in functional pathways associated with depression including ‘Adrenergic-, GPCR-, cAMP-, and CREB/CREM-signaling’. Integrative gene expression analysis specifically links changes in amygdaloid intracellular signaling activity to the behavioral treatment response in Brd1+/- mice. Conclusions: Collectively, our study highlights the importance of BRD1 as a modulator of affective pathology and adds to our understanding of the molecular mechanisms underlying affective disorders and their treatment response.
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