Chronobiology Lab, Department of Zoology, Institute of Science, Banaras Hindu University, Varanasi, Uttar Pradesh 221005, India.
Chronobiology Lab, Department of Zoology, Institute of Science, Banaras Hindu University, Varanasi, Uttar Pradesh 221005, India.
Neuroscience. 2024 Apr 5;543:1-12. doi: 10.1016/j.neuroscience.2024.01.026. Epub 2024 Feb 13.
There has been a long history that chronic circadian disruption such as jet lag or shift work negatively affects brain and body physiology. Studies have shown that circadian misalignment act as a risk factor for developing anxiety and mood-related depression-like behavior. Till date, most studies focused on simulating jet lag in model animals under laboratory conditions by repeated phase advances or phase delay only, while the real-life conditions may differ. In the present study, adult male mice were subjected to simulated chronic jet lag (CJL) by alternately advancing and delaying the ambient light-dark (LD) cycle by 9 h every 2 days, thereby covering a total of 24 days. The effect of CJL was then examined for a range of stress and depression-related behavioral and physiological responses. The results showed that mice exposed to CJL exhibited depression-like behavior, such as anhedonia. In the open field and elevated plus maze test, CJL-exposed mice showed increased anxiety behavior compared to LD control. In addition, CJL-exposed mice showed an increased level of serum corticosterone and proinflammatory cytokine, TNF-α in both serum and hippocampus. Moreover, CJL-exposed mice exhibited a reduction in structural complexity of hippocampal CA1 neurons along with decreased expression of neurotrophic growth factors, BDNF and NGF in the hippocampus compared to LD control. Taken together, our findings suggest that simulated chronic jet lag adversely affects structural and functional complexity in hippocampal neurons along with interrelated endocrine and inflammatory responses, ultimately leading to stress, anxiety, and depression-like behavior in mice.
长期以来，慢性昼夜节律紊乱（如时差或轮班工作）对大脑和身体生理机能的负面影响已被广泛研究。研究表明，昼夜节律失调是导致焦虑和情绪相关抑郁样行为的一个风险因素。迄今为止，大多数研究都集中在通过重复相位提前或相位延迟来模拟实验室条件下的模型动物中的时差，而现实生活中的情况可能有所不同。在本研究中，成年雄性小鼠通过每隔两天交替提前和延迟环境光照-黑暗（LD）周期 9 小时来模拟慢性时差（CJL），总共持续 24 天。然后检查 CJL 对一系列应激和抑郁相关行为和生理反应的影响。结果表明，暴露于 CJL 的小鼠表现出类似抑郁的行为，如快感缺失。在旷场和高架十字迷宫测试中，与 LD 对照组相比，CJL 暴露组的小鼠表现出焦虑行为增加。此外，与 LD 对照组相比，CJL 暴露组的小鼠血清皮质酮和促炎细胞因子 TNF-α的水平升高，血清和海马中均升高。此外，与 LD 对照组相比，CJL 暴露组的小鼠海马 CA1 神经元的结构复杂性降低，海马中的神经营养生长因子 BDNF 和 NGF 的表达降低。总之，我们的研究结果表明，模拟慢性时差会对海马神经元的结构和功能复杂性以及相关的内分泌和炎症反应产生不利影响，最终导致小鼠出现应激、焦虑和抑郁样行为。
