The role of the GABAA receptor Alpha 1 subunit in the ventral hippocampus in stress resilience
The role of the GABAA receptor Alpha 1 subunit in the ventral hippocampus in stress resilience
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DOI：
10.1038/s41598-019-49824-4
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发表时间：
2019-09-18
影响因子：
4.6
通讯作者：
Richter-Levin, G.
中科院分区：
文献类型：
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作者：
Ardi, Z.;Richter-Levin, A.;Richter-Levin, G.
青春期前应激增加创伤后应激障碍(PTSD)的易感性。我们以前已经证明，在青春期前应激后立即进行丰富环境(EE)干预可以保护成年后免受创伤的影响。在这里，我们研究了如果在成年后暴露于创伤后，暴露于EE是否也是有益的。我们最近发现，暴露于幼年应激和水下创伤(UWT)与腹侧海马区GABA(A)受体亚单位α1表达增加有关。然而，区分受影响和未受影响的个体，这种增加的表达仅限于压力暴露、行为未受影响的个体，这表明阿尔法1的表达上调是一种潜在的弹性机制。我们现在研究了EE诱导的恢复力是否使腹侧海马区阿尔法1表达的增加在以后的生活中面临创伤时是多余的。成年大鼠暴露于UWT，并预先暴露于幼年应激，并在四周后在开阔场地和高架+迷宫范式中进行测试。青年时期的EE暴露可以预防青春期前应激诱导的脆弱性，但如果在成年后进行UWT，则不能。此外，少年EE暴露可阻止创伤相关的阿尔法1表达水平的增加。我们的发现强调了早期干预的重要性，以减少成年后发展成精神病的可能性。
Pre-pubertal stress increases post-traumatic stress disorder (PTSD) susceptibility. We have previously demonstrated that enriched environment (EE) intervention immediately after pre-pubertal stress protects from the effects of trauma in adulthood. Here, we examined whether exposure to EE would also be beneficial if applied after exposure to trauma in adulthood. We have recently shown that exposure to juvenile stress and under-water trauma (UWT) is associated with increased expression of GABA(A) receptor subunit alpha 1 in the ventral hippocampus. However, differentiating between affected and unaffected individuals, this increased expression was confined to stress-exposed, behaviorally unaffected individuals, suggesting upregulation of alpha 1 expression as a potential mechanism of resilience. We now examined whether EE-induced resilience renders increased expression of alpha 1 in the ventral hippocampus redundant when facing a trauma later in life. Adult rats were exposed to UWT, with pre-exposure to juvenile stress, and tested in the open field and elevated plus maze paradigms four weeks later. EE exposure during juvenility prevented pre-pubertal stress-induced vulnerability, but not if performed following UWT in adulthood. Furthermore, juvenile EE exposure prevented the trauma-associated increase in alpha 1 expression levels. Our findings emphasize the importance of early interventions in order to reduce the likelihood of developing psychopathologies in adulthood.