Department of Physiology, College of Basic Medical Sciences, Jilin University, Changchun, China.
Department of Neurology and Neuroscience Research Center, The First Hospital of Jilin University, Changchun, China.
Genes Brain Behav. 2021 Apr;20(4):e12702. doi: 10.1111/gbb.12702. Epub 2020 Oct 12.
Circadian rhythm dysfunction is primary symptom of depression and is closely related to depression onset. The role of the lateral habenula (LHb) of the thalamus in the pathogenesis of depression has been a research topic of great interest. The neuronal activity of this structure has circadian characteristics, which are related to the regulation of circadian rhythms. However, in depression model of rats, the role of clock genes in the LHb has not been assessed. To address this gap, we used a clomipramine (CLI) injection-induced depression model in rats to assess the daily expression of rhythmic genes in the LHb and depression-like behavior in rats at multiple time points. In determining the role of the Per2 gene in the development of depression-like behavior in the LHb, we found that the expression of this clock gene differed in a circadian manner. Per2 expression was also significantly decreased in CLI-treated rats in late afternoon (17:00) and in the middle of the night (1:00). Furthermore, silencing Per2 in the LHb of normal rats induced depression-like behavior at night, suggesting that Per2 may play an important role in the pathogenesis of depression. Collectively, these results indicate that decreased Per2 expression in the LHb may be related to increased depression-like behavior at night in depression model of rats.
昼夜节律紊乱是抑郁症的主要症状，与抑郁症的发病密切相关。丘脑外侧缰核（LHb）在抑郁症发病机制中的作用一直是一个研究热点。该结构的神经元活动具有昼夜节律特征，与昼夜节律的调节有关。然而，在大鼠的抑郁症模型中，尚未评估时钟基因在 LHb 中的作用。为了解决这一差距，我们使用氯米帕明（CLI）注射诱导的大鼠抑郁症模型，在多个时间点评估 LHb 中的节律基因的日常表达和大鼠的抑郁样行为。在确定 Per2 基因在 LHb 中发展为抑郁样行为中的作用时，我们发现该时钟基因的表达呈昼夜节律变化。CLI 处理的大鼠在傍晚（17:00）和午夜（1:00）的 Per2 表达也明显降低。此外，在正常大鼠的 LHb 中沉默 Per2 会在夜间诱导出抑郁样行为，表明 Per2 可能在抑郁症的发病机制中发挥重要作用。总之，这些结果表明，LHb 中 Per2 表达的减少可能与大鼠抑郁症模型中夜间抑郁样行为的增加有关。
