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Restoring Circadian Rhythms in the Paraventricular Nucleus Reverses the Epigenetic Clock of Multi Tissues in Aging Mice. [RRBS]

ABSTRACT: The decline of behavioral and metabolic rhythms with aging underscores the critical role of circadian regulation in health and longevity. Restoring circadian rhythms has recently emerged as a promising strategy to combat aging-associated disorders. Epigenome remodeling and gene expression changes during cellular senescence. These epigenomic changes have been widely recognized as hallmarks of aging. Therefore, we examined the DNA methylation levels in aging mice with 3dA treatment and chemogenetic manipulation in PVN. Our results suggest that enhancing circadian rhythm amplitude in paraventricular nucleus (PVN) neurons by 3’-deoxyadenosine (3dA) and chemogenetics significantly reverses the epigenetic clock of multi tissues in aging mice.

ORGANISM(S): Mus musculus

PROVIDER: GSE286302 | GEO | 2026/03/08

REPOSITORIES: GEO

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Project description:Rationale Electroconvulsive seizure (ECS) therapy is a nonchemical treatment for depression. Since ECS up-regulates expression of c-Fos in the paraventricular nucleus of hypothalamus (PVN), the function of which is frequently influenced in depression, we hypothesized that ECS modulates functions of the PVN and contributes to its antidepressant effects. Objectives To identify gene expression changes in the mouse PVN by ECS treatment Material and methods First, we established a method to amplify nucleotides from small quantities of RNA. Mice received one shock of ECS and their brains were collected at 2 or 6 h after shock. The PVN was microdissected from dehydrated brain sections, its total RNA was extracted and microarray analysis was applied. Results At 2 h after ECS, 2.6% (589 genes) of the probes showed more than 2-fold decrease, and 0.9% (205 genes) showed more than 2-fold increase. To confirm the expression changes, genes showing differential expression with a wide range in the microarray were analyzed by qPCR. Among the genes with more than 2-fold change by ECS, down-regulated 94 genes and up-regulated 24 genes have been reported the association with anxiety, bipolar disorder or mood disorder by the Ingenuity knowledge database. The groups of down-regulated genes, which are suggested to modulate the function of the PVN or associate to psychiatric disorders, include neuropeptides (Cck), kinases (Prkcb, Prkcc, Camk2a), transcription factors (Bcl6, Tbr1), transporters (Aqp4) and others (Fmr1). Conclusion The present results indicate that ECS treatment can modulate the functions of PVN via a series of gene expression changes, and may contribute to its antidepressant effects at least in part. Mice received one shock of ECS and their brains were collected at 2 h (PVN_ECS2h_1, PVN_ECS2h_2) or 6 h after shock (PVN_ECS6h_1, PVN_ECS6h_2). The brains of sham-treated animals were collected at 2 h after treatment (PVN_sham_1, PVN_sham_2). The PVN was microdissected from dehydrated brain sections, and its total RNA was extracted. RNA samples from two or three animals were pooled to minimize the impact of biological variance. After nucleotide amplification by the ovation amplification, the gene expression profiles were obtained by the Affymetrix microarray analysis. The microarray analysis was performed twice using different sets of animals.

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Restoring Circadian Rhythms in the Paraventricular Nucleus Reverses the Epigenetic Clock of Multi Tissues in Aging Mice. [RRBS]

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