背景:抑郁症是全球残疾的主要原因,是全球疾病总体负担的主要原因,但对其病因了解甚少。据报道,生物节律中断,在缩短光照时间和完全黑暗方面,会导致动物的类似抑郁的行为。据报道,蓝光对褪黑激素有抑制作用,被认为是重要的生物钟节律生物标志物。在本研究中,我们研究了蓝光剥夺对沙鼠抑郁样行为的影响,并探讨了潜在的机制。
方法:将沙鼠置于白光下,并带有滤光片以阻挡蓝光或不带有滤光片。观察了沙鼠的行为。生物节律,5-HT,分析了下丘脑-垂体-肾上腺(HPA)轴和黑视素途径。
结果:我们发现蓝光剥夺(BLD)在沙鼠中引起抑郁样行为。褪黑素失去了节奏,BLD组早晨皮质酮(CORT)水平下降。BLD后下丘脑促肾上腺皮质激素释放激素(CRH)降低,血清促肾上腺皮质激素(ACTH)/CORT降低。此外,血清和脑中的5-HT在BLD后降低。此外,BLD影响蓝光敏感蛋白黑视蛋白及其通路,随着黑视素蛋白的下调,PKCα,和c-Fos以及c-fos和trpc3的mRNA水平以及蛋白p-PKCα的上调。
结论:我们的研究结果表明,BLD可能在沙鼠中产生抑郁样行为。褪黑素心律失常,HPA轴异常,5-HT降低和黑素通路改变可能与沙土鼠抑郁行为表型有关。
BACKGROUND: Depression is a leading cause of disability worldwide and is a major contributor to the overall global burden of disease, but its etiology is poorly understood. It has been reported that a disrupted biological rhythm, in terms of a shortened light duration and total darkness, can cause depression-like behaviors in animals. Blue light was reported to have an inhibitory effect on melatonin, which is considered an important clock rhythm biomarker. In the present study, we investigated the effects of blue light deprivation on depressive-like behaviors in
gerbils and explored the underlying mechanisms.
METHODS: Gerbils were housed under white light with a filter to block the blue light or without a filter. The behaviors of the
gerbils were observed. The biological rhythm, 5-HT, hypothalamic-pituitary-adrenal (HPA) axis and melanopsin pathway were analyzed.
RESULTS: We found that blue light deprivation (BLD) induced depression-like behavior in
gerbils. Melatonin lost its rhythm, and corticosterone (CORT) levels decreased in the morning in the BLD group. Lower corticotropin-releasing hormone (CRH) in the hypothalamus and lower adrenocorticotropin hormone (ACTH)/CORT in serum were observed after BLD. Furthermore, 5-HT in the serum and brain were decreased after BLD. Additionally, BLD affected the blue light sensitivity protein melanopsin and its pathway, with downregulation of the proteins melanopsin, PKCα, and c-Fos and the mRNA levels of c-fos and trpc3 and upregulation of the protein p-PKCα.
CONCLUSIONS: Our findings indicated that BLD might produce depression-like behaviors in
gerbils. Melatonin arrhythmicity, HPA axis abnormalities, 5-HT decreases and melanopsin pathway changes might be associated with the depression behavioral phenotype in gerbils.