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幼年压力暴露会诱导大鼠 GABA 能系统的表观遗传改变。

Exposure to Juvenile Stress Induces Epigenetic Alterations in the GABAergic System in Rats.

机构信息

Sagol Department of Neurobiology, Faculty of Natural Sciences, University of Haifa, 199 Aba Khoushy Ave. Mount Carmel, Haifa 3498838, Israel.

Department of Human Biology, Faculty of Natural Sciences, University of Haifa, 199 Aba Khoushy Ave. Mount Carmel, Haifa 3498838, Israel.

出版信息

Genes (Basel). 2023 Feb 23;14(3):565. doi: 10.3390/genes14030565.

Abstract

Epigenetics is a gene-environment interaction mechanism, manifested mostly through changes in regulatory gene expression. Stress is an established environmental factor known to induce epigenetic changes. This study aimed to assess the long-term effect of stress as juveniles, or juvenile and adult stress, on alterations in glutamic acid decarboxylase genes (, ). We assessed DNA methylation and RNA expression in four rat groups: (1) control group, (2) juvenile stress group sacrificed two days following stress exposure (JSe) (RNA only), (3) juvenile stress group sacrificed as adults (JS), and (4) juvenile and adult stress group (JS + AS). Three different areas of the brain were examined in each group: the dorsal dentate gyrus (dDG), the dorsal CA1 (dCA1), and the basolateral amygdala (BLA). A significantly low methylation level of in the BLA was observed among the JS group, followed by almost complete recovery among the JS + AS group. However, in dDG, an opposite trend was captured, and higher methylation was found in JS. In addition, RNA levels were found to be decreased in JS compared to JSe and JS + AS. These findings can point to a possible mechanism: while juvenile stress may enhance a better coping strategy with life challenges, additional stress in adulthood may trigger a contradictory response, either beneficial or harmful.

摘要

表观遗传学是一种基因-环境相互作用机制,主要表现为调节基因表达的变化。应激是一种已确定的环境因素,已知会诱导表观遗传改变。本研究旨在评估应激作为青少年(或青少年和成年应激)对谷氨酸脱羧酶基因(,)改变的长期影响。我们评估了四个大鼠组的 DNA 甲基化和 RNA 表达:(1)对照组,(2)应激暴露后两天处死的青少年应激组(仅 RNA),(3)成年应激组(JS),和(4)青少年和成年应激组(JS + AS)。在每组中检查了大脑的三个不同区域:背齿状回(dDG)、背侧 CA1(dCA1)和基底外侧杏仁核(BLA)。在 JS 组中观察到 BLA 中 的低甲基化水平显著降低,随后在 JS + AS 组中几乎完全恢复。然而,在 dDG 中,发现了相反的趋势,并且在 JS 中发现了更高的 甲基化。此外,与 JSe 和 JS + AS 相比,JS 中的 RNA 水平发现降低。这些发现可能指向一种可能的机制:虽然青少年应激可能增强了应对生活挑战的更好应对策略,但成年后的额外应激可能会引发有益或有害的相反反应。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/91b7/10048220/39de44a49bee/genes-14-00565-g001.jpg

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