ArticleMolecular neurobiology2019
Stress-Induced Epigenetic Changes in Hippocampal Mkp-1 Promote Persistent Depressive Behaviors.
Article in Molecular neurobiology, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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12 citing papers in PubMed, 30 citations in OpenAlex.
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- GR/P300 Regulates MKP1 Signaling Pathway and Mediates Depression-like Behavior in Prenatally Stressed Offspring.Molecular neurobiology · 2024Article
- Epigenetic analyses in forensic medicine: future and challenges.International journal of legal medicine · 2024Review
- Down-regulation of MKP-1 in hippocampus protects against stress-induced depression-like behaviors and neuroinflammation.Translational psychiatry · 2024Article
- Inactivation of ERK1/2 Signaling in Dopaminergic Neurons by Map Kinase Phosphatase MKP3 Regulates Dopamine Signaling and Motivation for Cocaine.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2024Article
- Extracellular Vesicles Released byExperimental neurobiology · 2023Article
- Differential expression of Dusp1 and immediate early response genes in the hippocampus of rats, subjected to forced swim test.Scientific reports · 2023Article
- Identification of mitogen-activated protein kinase phosphatase-1 (MKP-1) protein partners using tandem affinity purification and mass spectrometry.Pharmacological reports : PR · 2023Article
- Aging-Dependent Downregulation of SUV39H1 Histone Methyltransferase Increases Susceptibility to Stress-Induced Depressive Behavior.Molecular neurobiology · 2021Article
- Hyperoxygenation Treatment Reduces Beta-amyloid Deposition via MeCP2-dependent Upregulation of MMP-2 and MMP-9 in the Hippocampus of Tg-APP/PS1 Mice.Experimental neurobiology · 2021Article
- Aging increases vulnerability to stress-induced depression via upregulation of NADPH oxidase in mice.Communications biology · 2020Article
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Chronic stress induces persistent depressive behaviors. Stress-induced transcriptional alteration over the homeostatic range in stress hormone-sensitive brain regions is believed to underlie long-lasting depressive behaviors. However, the detailed mechanisms by which chronic stress causes those adaptive changes are not clearly understood. In the present study, we investigated whether epigenetic changes regulate stress-induced depressive behaviors. We found that chronic stress in mice downregulates the epigenetic factors HDAC2 and SUV39H1 in the hippocampus. A series of follow-up analyses including ChIP assay and siRNA-mediated functional analyses reveal that glucocorticoids released by stress cumulatively increase Mkp-1 expression in the hippocampus, and increased Mkp-1 then debilitates p-CREB and PPARγ, which in turn suppress the epigenetic factors HDAC2 and SUV39H1. Furthermore, HDAC2 and SUV39H1 normally suppress the transcription of the Mkp-1, and therefore the reduced expression of HDAC2 and SUV39H1 increases Mkp-1 expression. Accordingly, repeated stress progressively strengthens a vicious cycle of the Mkp-1 signaling cascade that facilitates depressive behaviors. These results suggest that the hippocampal stress adaptation system comprising HDAC2/SUV39H1-regulated Mkp-1 signaling network determines the vulnerability to chronic stress and the maintenance of depressive behaviors.
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