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Effect of chronic restraint stress or repeated activation of PVN neurons responding to restraint stress on gene expression of white adipose tissues (iWAT and eWAT) during adipogenesis of mice

ABSTRACT: Comorbid depression and type 2 diabetes (T2D) is associated with more severe symptoms, higher suicide risk and poorer prognosis than those with either disease alone. However, the mechanisms underlying this comorbidity remain unclear. Here, we describe a brain–sympathetic nerve–adipose circuit originating in the hypothalamic paraventricular nucleus (PVN) that is crucial for the depressive-like behaviours and insulin resistance induced by chronic restraint stress. A subset of PVN neurons that were traced from WAT and activated under restraint stress, and chemogenetic manipulations demonstrated the sufficiency and necessity of those PVN neurons for changes in sympathetic innervation of adipose tissue and subsequent depression and insulin resistance induced by chronic stress. We further identify candidate adipokines for the development of depression and insulin resistance, and clarify the molecular mechanism by which the dynamics of sympathetic tone are translated into changes in the expression of candidate adipokines.

ORGANISM(S): Mus musculus

PROVIDER: GSE216370 | GEO | 2022/10/29

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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Effect of chronic restraint stress or repeated activation of PVN neurons responding to restraint stress on gene expression of white adipose tissues (iWAT and eWAT) during adipogenesis of mice

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