The Molecular Biology Laboratory.
Mental Health Center, Zhejiang University School of Medicine.
Neuroreport. 2021 Jan 6;32(1):8-15. doi: 10.1097/WNR.0000000000001554.
Melatonin is a hormone synthesized and secreted by the pineal gland with the effect of regulating sleep rhythm. Circadian and sleep disturbances may be central for understanding the pathophysiology and treatment of depression. Recently, the melatonergic system has been implicated in the pathophysiology and treatment of depression. In this study, we observed the effects of melatonin on depression-like behavior induced by chronic unpredictable mild stress (CUMS) in rats, and its molecular mechanism was explored. Adult male Sprague-Dawley rats were exposed to CUMS for 4 weeks. Melatonin or saline was injected intraperitoneally. Behavioral changes of Sprague-Dawley rats were detected by the open field test, sugar preference test, elevated O maze test and forced swimming test. In addition, the plasma corticosterone level and the expression of endoplasmic reticulum stress-related protein in the hippocampus of rats were measured. Compared with the control group, the CUMS-exposed Sprague-Dawley rats showed depression-like behavior, which was significantly improved by melatonin treatment. Moreover, CUMS induced endoplasmic reticulum stress and JNK phosphorylation in the hippocampus. Melatonin treatment could significantly reverse the endoplasmic reticulum stress and JNK phosphorylation induced by CUMS. These results suggest that melatonin improves depression-like behavior by inhibiting endoplasmic reticulum stress induced by CUMS. This study demonstrates that melatonin can improve depression-like behavior induced by CUMS, which may be related to the inhibition of endoplasmic reticulum stress and JNK phosphorylation in rat hippocampus.
褪黑素是由松果体合成和分泌的一种激素，具有调节睡眠节律的作用。昼夜节律和睡眠紊乱可能是理解抑郁症病理生理学和治疗的关键。最近，褪黑素能系统与抑郁症的病理生理学和治疗有关。在这项研究中，我们观察了褪黑素对慢性不可预测轻度应激（CUMS）诱导的大鼠抑郁样行为的影响，并探讨了其分子机制。成年雄性 Sprague-Dawley 大鼠接受 CUMS 处理 4 周。褪黑素或生理盐水通过腹腔注射给药。通过旷场试验、糖水偏好试验、高架十字迷宫试验和强迫游泳试验检测 Sprague-Dawley 大鼠的行为变化。此外，测量了大鼠血浆皮质酮水平和海马内质网应激相关蛋白的表达。与对照组相比，CUMS 暴露的 Sprague-Dawley 大鼠表现出抑郁样行为，褪黑素治疗可显著改善这种行为。此外，CUMS 诱导了海马内质网应激和 JNK 磷酸化。褪黑素治疗可显著逆转 CUMS 诱导的内质网应激和 JNK 磷酸化。这些结果表明，褪黑素通过抑制 CUMS 诱导的内质网应激改善抑郁样行为。本研究表明，褪黑素可改善 CUMS 诱导的抑郁样行为，这可能与抑制大鼠海马内质网应激和 JNK 磷酸化有关。
