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青少年和成年期大鼠的社会行为和表观遗传状态:早期生活应激性社会经历的贡献。

Social Behaviour and Epigenetic Status in Adolescent and Adult Rats: The Contribution of Early-Life Stressful Social Experience.

机构信息

Behavioural Neuroscience Laboratory, Department of Animal Science, School of Life Sciences, Bharathidasan University, Tiruchirappalli, 620024, India.

出版信息

Cell Mol Neurobiol. 2019 Apr;39(3):371-385. doi: 10.1007/s10571-019-00655-x. Epub 2019 Feb 1.

Abstract

Early-life experiences have been linked to individual's epigenetic status and social behaviour. Therefore, the present study aims to test whether the presence of mother suppress the early-life stressful social experience (SSE)-induced effect on social behaviour of adolescent and adult rats, and associated epigenetic changes. To test this, experimental groups [maternally separated pups (MSP)/pups with their mother (M+P)] were allowed to experience the presence of a stranger (ST), and then their social behaviour was compared with the maternal separated (MS) and control (Con) group. We observed that MS, MSP-ST group showed less social interaction with the unknown conspecifics than known conspecifics compared to other groups. Subsequently, we found that SSE elevated the level of DNA methyltransferases (Dnmt3a), ten-eleven translocation (Tet3), methyl-CpG-binding protein-2 (MeCP2) and Repressor Element-1 Silencing Transcription Factor (REST) in amygdala of adolescent and adult MS, MSP-ST groups compared to other groups. As expected, SSE altered the histone (H3) lysine (K14/K9) acetylation (ac) and H3K4/K9 methylation (me2/me3). SSE decreased the level of H3K14ac and H3K9ac in adolescents and then increased in adults. Interestingly, H3K4me2/me3 levels were elevated in adolescent and adults. Whereas H3K9me2/me3 shows contrasting pattern in adolescent, but H3K9me2/me3 levels were increased in adults. In addition, the expression of brain-derived neurotrophic factor (BDNF) was reduced in MS, MSP-ST groups' adolescent and adult rats. Observed correlation between epigenetic changes and social behaviour possibly contributed by early-life SSE in the absence of mother, but mother's presence suppresses the effect of early-life SSE.

摘要

早期生活经历与个体的表观遗传状态和社会行为有关。因此,本研究旨在测试母亲的存在是否能抑制早期生活应激性社会体验(SSE)对青少年和成年大鼠社会行为的影响及其相关的表观遗传变化。为此,实验组[母婴分离的幼鼠(MSP)/与母亲在一起的幼鼠(M+P)]被允许接触陌生的同类(ST),然后比较它们与母婴分离(MS)和对照组(Con)的社会行为。我们发现,与其他组相比,MS、MSP-ST 组的幼鼠与陌生同类的互动较少,而与熟悉同类的互动较多。随后,我们发现 SSE 增加了青少年和成年 MS、MSP-ST 组杏仁核中的 DNA 甲基转移酶(Dnmt3a)、十号十一号转位酶(Tet3)、甲基-CpG 结合蛋白-2(MeCP2)和阻遏元件-1 沉默转录因子(REST)的水平,而对照组则没有。如预期的那样,SSE 改变了组蛋白(H3)赖氨酸(K14/K9)乙酰化(ac)和 H3K4/K9 甲基化(me2/me3)。SSE 降低了青少年的 H3K14ac 和 H3K9ac 水平,然后在成年时增加。有趣的是,H3K4me2/me3 水平在青少年和成年时都升高了。而 H3K9me2/me3 在青少年时表现出相反的模式,但在成年时 H3K9me2/me3 水平升高。此外,MS、MSP-ST 组的青少年和成年大鼠的脑源性神经营养因子(BDNF)表达减少。早期生活应激性 SSE 缺失时,表观遗传变化与社会行为之间的相关性可能是由其引起的,但母亲的存在抑制了早期生活应激性 SSE 的作用。

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