Abstract:
Nocturnal light pollution, an underappreciated mood manipulator, disturbs the circadian rhythms of individuals in modern society. Preclinical and clinical studies have suggested that exposure to lights at night (LANs) results in depression-like phenotypes. However, the mechanism underlying the action of LANs remains unclear. Therefore, this study explored the potential influence of LANs on depression-related brain regions by testing brain-derived neurotrophic factor (BDNF), synaptic transmission, and plasticity in male Sprague-Dawley rats. Depression-related behavioral tests, enzyme-linked immunosorbent assays, and intracellular and extracellular electrophysiological recordings were performed. Resultantly, rats exposed to either white or blue LAN for 5 or 21 days exhibited depression-like behaviors. Both white and blue LANs reduced BDNF expression in the medial prefrontal cortex (mPFC) and ventrolateral periaqueductal gray (vlPAG). Moreover, both lights at night (LANs) elevated the plasma corticosterone levels. Pharmacologically, the activation of glucocorticoid receptors mimics the LAN-mediated effects on depression-like behaviors and reduces BDNF levels, whereas the inhibition of glucocorticoid receptors blocks LAN-mediated behavioral and molecular actions. Electrophysiologically, both LANs attenuated the stimulation-response curve, increased the paired-pulse ratio, and decreased the frequency and amplitude of miniature excitatory postsynaptic currents in the vlPAG. In the mPFC, LANs attenuate long-term potentiation and long-term depression. Collectively, these results suggested that white and blue LANs disturbed BDNF expression, synaptic transmission, and plasticity in the vlPAG and mPFC in a glucocorticoid-dependent manner. The results of the present study provide a theoretical basis for understanding the effects of nocturnal light exposure on depression-like phenotypes.
摘要:
夜间光污染,一个被低估的情绪操纵者,扰乱现代社会个体的昼夜节律。临床前和临床研究表明,夜间暴露于灯光(LAN)会导致抑郁样表型。然而,局域网的作用机制尚不清楚。因此,本研究通过检测脑源性神经营养因子(BDNF),探讨了LAN对抑郁症相关脑区的潜在影响,突触传递,雄性Sprague-Dawley大鼠的可塑性。抑郁相关行为测试,酶联免疫吸附测定,并进行细胞内和细胞外电生理记录。结果,暴露于白色或蓝色LAN5或21天的大鼠表现出抑郁样行为。白色和蓝色LAN均降低了内侧前额叶皮质(mPFC)和腹外侧导水管周围灰色(vlPAG)中的BDNF表达。此外,夜间两灯(LAN)都升高了血浆皮质酮水平。药理学上,糖皮质激素受体的激活模拟LAN介导的对抑郁样行为的影响,并降低BDNF水平,而抑制糖皮质激素受体阻断LAN介导的行为和分子作用。电生理,两个LAN都衰减了刺激-反应曲线,增加了成对脉冲比,并降低了vlPAG中微型兴奋性突触后电流的频率和幅度。在mPFC中,LAN减弱长期增强和长期抑郁。总的来说,这些结果表明,白色和蓝色LAN干扰了BDNF的表达,突触传递,和糖皮质激素依赖性方式在vlPAG和mPFC中的可塑性。本研究结果为了解夜间光照对抑郁样表型的影响提供了理论依据。