Previous investigations have implicated the basolateral amygdala (BLA) epigenetic mechanisms in the pathophysiology of depression. SIRT1 is a NAD+-dependent class III histone deacetylase, widely expresses in BLA. However, epigenetic mechanisms in the BLA under the regulation of SIRT1 in the depression are largely uncharacterized. Under the chronic unpredictable chronic mild stress (CUMS) mouse model, we used adeno-associated viral vectors (AAV) that encoded SIRT1-shRNA or SIRT1 to specifically knockdown or overexpress SIRT1 in BLA neurons, respectively. CUMS procedure induced significant depression symptoms including the decreased sucrose preference, the less bodyweight gained, the decreased immobile latency and the increased immobile time both in forced swim test (FST) and tail suspension test (TST). Knockdown of SIRT1 in BLA glutamatergic neurons reversed these depression-like behaviors and restored the synaptic abnormalities. Overexpression of SIRT1 in BLA glutamatergic neurons induced depression-like behaviors in non-stressed control mice. The result of protein expressions and ultrastructural changes were consistent with the behavioral results. Our study suggested that downregulation of SIRT1 in BLA has certain beneficial effect on CUMS-induced depression-like behaviors such as anorexia, anhedonia, hopelessness and despair. In addition, the increased expression of SIRT1 may be the immediate cause of depressive-like symptoms. The abnormal expression of SIRT1 may affect the transcriptional regulation mechanism and signaling protein acetylation, affecting neuroplasticity and ultimately contribute to MDD. In the stress-susceptible mice, these two mechanisms may co-exist, but the specific mechanism needs further research.

中文翻译：

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基底外侧杏仁核中SIRT1在小鼠抑郁样行为中的作用

先前的研究表明基底外侧杏仁核 (BLA) 表观遗传机制与抑郁症的病理生理有关。SIRT1 是 NAD+ 依赖的 III 类组蛋白脱乙酰酶，在 BLA 中广泛表达。然而，在抑郁症中受 SIRT1 调控的 BLA 的表观遗传机制在很大程度上没有得到表征。在慢性不可预测的慢性轻度应激 (CUMS) 小鼠模型下，我们使用编码 SIRT1-shRNA 或 SIRT1 的腺相关病毒载体 (AAV) 分别在 BLA 神经元中特异性敲低或过表达 SIRT1。在强迫游泳测试 (FST) 和悬尾测试 (TST) 中，CUMS 程序引起了显着的抑郁症状，包括蔗糖偏好降低、体重增加较少、不动潜伏期减少和不动时间增加。敲除 BLA 谷氨酸能神经元中的 SIRT1 逆转了这些抑郁样行为并恢复了突触异常。BLA 谷氨酸能神经元中 SIRT1 的过度表达在非应激对照小鼠中诱导抑郁样行为。蛋白质表达和超微结构变化的结果与行为结果一致。我们的研究表明，BLA 中 SIRT1 的下调对 CUMS 诱导的抑郁样行为如厌食、快感缺乏、绝望和绝望具有一定的有益作用。此外，SIRT1 表达的增加可能是抑郁样症状的直接原因。SIRT1的异常表达可能影响转录调控机制和信号蛋白乙酰化，影响神经可塑性并最终促成MDD。在应激敏感小鼠中，