Laboratory of Biology and Development of the Nervous System, School of Health and Life Sciences, Pontifical Catholic University of Rio Grande do Sul, Ipiranga Av. 6681, 90619-900 Porto Alegre, Brazil.
Laboratory of Biology and Development of the Nervous System, School of Health and Life Sciences, Pontifical Catholic University of Rio Grande do Sul, Ipiranga Av. 6681, 90619-900 Porto Alegre, Brazil; Institute of Geriatrics and Gerontology, Pontifical Catholic University of Rio Grande do Sul, Ipiranga Av. 6690, 90610-000 Porto Alegre, Brazil.
Behav Brain Res. 2023 Mar 12;441:114303. doi: 10.1016/j.bbr.2023.114303. Epub 2023 Jan 16.
Social deprivation can be stressful for group-living mammals. On the other hand, an amazing response of these animals to stress is seeking social contact to give and receive joint protection in threatening situations. We explored the effects of social isolation and social support on epigenetic and behavioral responses to chronic stress. More specifically, we investigated the behavioral responses, corticosterone levels, BDNF gene expression, and markers of hippocampal epigenetic alterations (levels of H3K9 acetylation and methylation, H3K27 methylation, HDAC5, DNMT1, and DNMT3a gene expressions) in middle-aged adult rats maintained in different housing conditions (isolation or accompanied housing) and exposed to the chronic unpredictable stress protocol (CUS). Isolation was associated with decreased basal levels of corticosterone, impaired long-term memory, and decreased expression of the BDNF gene, besides altering the balance of H3K9 from acetylation to methylation and increasing the DNMT1 gene expression. The CUS protocol decreased H3K9 acetylation, besides increasing H3K27 methylation and DNMT1 gene expression, but had no significant effects on memory and BDNF gene expression. Interestingly, the effects of CUS on corticosterone and HDAC5 gene expression were seen only in isolated animals, whereas the effects of CUS on DNMT1 gene expression were more pronounced in isolated than accompanied animals. In conclusion, social isolation in middle age showed broader effects than chronic unpredictable stress on behavioral and epigenetic alterations potentially associated with decreased BDNF expression. Moreover, social support prevented the adverse effects of CUS on HPA axis functioning, HDAC5, and DNMT1 gene expressions.
社会剥夺会对群居哺乳动物造成压力。另一方面，这些动物对压力的惊人反应是寻求社会接触，以便在威胁情况下给予和接受共同保护。我们探讨了社会隔离和社会支持对慢性应激的表观遗传和行为反应的影响。更具体地说，我们研究了中年成年大鼠在不同的饲养条件（隔离或结伴饲养）下的行为反应、皮质酮水平、BDNF 基因表达以及海马表观遗传改变的标志物（H3K9 乙酰化和甲基化、H3K27 甲基化、HDAC5、DNMT1 和 DNMT3a 基因表达）对慢性不可预测应激方案（CUS）的反应。隔离与皮质酮基础水平降低、长期记忆受损和 BDNF 基因表达减少有关，此外还改变了 H3K9 从乙酰化到甲基化的平衡，并增加了 DNMT1 基因的表达。CUS 方案除了增加 H3K27 甲基化和 DNMT1 基因表达外，还降低了 H3K9 乙酰化，但对记忆和 BDNF 基因表达没有显著影响。有趣的是，CUS 对皮质酮和 HDAC5 基因表达的影响仅见于隔离动物，而 CUS 对 DNMT1 基因表达的影响在隔离动物中比在结伴动物中更为明显。总之，中年时期的社会隔离对行为和表观遗传改变的影响比慢性不可预测应激更广泛，这些改变可能与 BDNF 表达减少有关。此外，社会支持可以防止 CUS 对 HPA 轴功能、HDAC5 和 DNMT1 基因表达的不利影响。
