Social isolation and social support at adulthood affect epigenetic mechanisms, brain-derived neurotrophic factor levels and behavior of chronically stressed rats
Social isolation and social support at adulthood affect epigenetic mechanisms, brain-derived neurotrophic factor levels and behavior of chronically stressed rats
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DOI：
10.1016/j.bbr.2019.03.025
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发表时间：
2019-07-02
影响因子：
2.7
通讯作者：
Bromberg, Elke
中科院分区：
文献类型：
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作者：
Borges, Juliano Viana;de Freitas, Betania Souza;Bromberg, Elke
脑源性神经营养因子（BDNF）的表观遗传调节为压力引起的功能障碍（例如精神疾病和认知能力下降）提供了一种可能的解释。有趣的是，社会支持可以防止其中一些影响，但人们对社会缓冲的机制知之甚少。相反，过早的隔离会加剧对压力源的反应，尽管其对成年期的影响仍不清楚。本研究调查了社会隔离和社会缓冲对长期应激的年轻成年大鼠海马表观遗传机制、BDNF 水平和行为反应的影响。雄性 Wistar 大鼠（3 个月）被分配到陪伴（配对）或隔离的住房中。一个月后，每组的一半人接受为期 18 天的慢性不可预测压力 (CUS) 方案。在陪伴的动物中，只有一只受到压力。行为分析包括开放领域、迷宫和抑制性回避任务。评估海马 H3K9 和 H4K12 乙酰化、HDAC5 表达和 BDNF 水平。隔离住房会增加 HDAC5 表达、降低 H3K9 和 H4K12 乙酰化、降低 BDNF 水平并损害长期记忆。压力会影响体重增加、诱发焦虑样行为并降低 AcK9H3 水平。仅在 HDAC5 表达方面观察到住房条件和社会压力之间的相互作用，该表达在隔离 + CUS 组中进一步增加，但在陪伴动物中保持不变。总之，成年后的社会隔离会导致表观遗传改变，并加剧慢性压力对 HDAC5 的影响。尽管如此，社会支持抵消了压力对 HDAC5 表达的不利影响。
Epigenetic modulation of brain-derived neurotrophic factor (BDNF) provides one possible explanation for the dysfunctions induced by stress, such as psychiatric disorders and cognitive decline. Interestingly, social support can be protective against some of these effects, but the mechanisms of social buffering are poorly understood. Conversely, early isolation exacerbates the responses to stressors, although its effects in adulthood remain unclear. This study investigated the effects of social isolation and social buffering on hippocampal epigenetic mechanisms, BDNF levels and behavioral responses of chronically stressed young adult rats. Male Wistar rats (3 months) were assigned to accompanied (paired) or isolated housing. After one-month half of each group was submitted to a chronic unpredictable stress (CUS) protocol for 18 days. Among accompanied animals, only one was exposed to stress. Behavioral analysis encompassed the Open field, plus maze and inhibitory avoidance tasks. Hippocampal H3K9 and H4K12 acetylation, HDAC5 expression and BDNF levels were evaluated. Isolated housing increased HDAC5 expression, decreased H3K9 and H4K12 acetylation, reduced BDNF levels, and impaired long-term memory. Stress affected weight gain, induced anxiety-like behavior and decreased AcK9H3 levels. Interactions between housing conditions and social stress were seen only for HDAC5 expression, which showed a further increase in the isolated + CUS group but remained constant in accompanied animals. In conclusion, social isolation at adulthood induced epigenetic alterations and exacerbated the effects of chronic stress on HDAC5. Notwithstanding, social support counteracted the adverse effects of stress on HDAC5 expression.