Enkephalin Knockdown in the Basolateral Amygdala Reproduces Vulnerable Anxiety-Like Responses to Chronic Unpredictable Stress
Enkephalin Knockdown in the Basolateral Amygdala Reproduces Vulnerable Anxiety-Like Responses to Chronic Unpredictable Stress
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DOI：
10.1038/npp.2013.316
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发表时间：
2014-04-01
影响因子：
7.6
通讯作者：
Drolet, Guy
中科院分区：
文献类型：
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作者：
Berube, Patrick;Poulin, Jean-Francois;Drolet, Guy
内源性脑啡肽（ENK）是参与慢性应激过程中应对方式自然发生变化并决定个体适应能力的潜在候选者。在这里，我们证明了有一个很大的差异，在个人的行为，以及在生理结果，在人口的Sprague道利大鼠进行3周的慢性不可预测的压力（CUS）。弹性和脆弱亚群的分离揭示了ENKergic脑回路中特定的长期神经适应。ENK mRNA的表达大大减少后基底外侧核杏仁核（BLAp）在脆弱的个人。相比之下，ENK mRNA水平在弹性和控制（无压力）的个人是相似的。另一组大鼠用于慢病毒介导的ENK敲低，以评估BLAp中ENK表达的减少是否再现了在脆弱个体中发现的行为障碍。与对照个体相比，特异性位于BLAp中的ENK敲除足以增加行为测试中的焦虑，例如社会互动和高架十字迷宫。这些结果表明，由BLAp中ENK能神经传递介导的特定神经适应是恢复力的关键调节因子，而BLAp中ENK的减少是适应不良机制，其介导了在CUS 3周后观察到的脆弱和恢复力之间的行为二分法。
The endogenous enkephalins (ENKs) are potential candidates participating in the naturally occurring variations in coping styles and determining the individual capacities for adaptation during chronic stress exposure. Here we demonstrate that there is a large variance in individual behavioral, as well as in physiological outcomes, in a population of Sprague Dawley rats subjected to 3 weeks of chronic unpredictable stress (CUS). Separation of resilient and vulnerable subpopulations reveals specific long-term neuroadaptation in the ENKergic brain circuits. ENK mRNA expression was greatly reduced in the posterior basolateral nucleus of amygdala (BLAp) in vulnerable individuals. In contrast, ENK mRNA levels were similar in resilient and control (unstressed) individuals. Another group of rats were used for lentiviral-mediated knockdown of ENK to assess whether a decrease of ENK expression in the BLAp reproduces the behavioral disturbances found in vulnerable individuals. ENK knockdown specifically located in the BLAp was sufficient to increase anxiety in the behavioral tests, such as social interaction and elevated plus maze when compared with control individuals. These results show that specific neuroadaptation mediated by the ENKergic neurotransmission in the BLAp is a key regulator of resilience, whereas a decrease of the ENK in the BLAp is a maladaptation mechanism, which mediates the behavioral dichotomy observed between vulnerable and resilient following 3 weeks of CUS.