Ge Jin-Fang, Xu Ya-Yun, Qin Gan, Peng Yao-Nan, Zhang Chao-Feng, Liu Xing-Rui, Liang Li-Chuan, Wang Zhong-Zheng, Chen Fei-Hu
Anhui Key Laboratory of Bioactivity of Natural Products, School of Pharmacy, Anhui Medical University Anhui, China.
Department of Clinical Medicine, The Second Clinical College of Anhui Medical University Anhui, China.
Front Neurosci. 2015 Nov 10;9:429. doi: 10.3389/fnins.2015.00429. eCollection 2015.
Depression is a multicausal disorder and has been associated with metabolism regulation and immuno-inflammatory reaction. The anorectic molecule nesfatin-1 has recently been characterized as a potential mood regulator, but its precise effect on depression and the possible mechanisms remain unknown, especially when given peripherally. In the present study, nesfatin-1 was intraperitoneally injected to the rats and the depression-like behavior and activity of the hypothalamic-pituitary-adrenal (HPA) axis were evaluated. The plasma concentrations of nesfatin-1, interleukin 6 (IL-6), and C-reactive protein (CRP); and the hypothalamic expression levels of nesfatin-1, synapsin I, and synaptotagmin I mRNA were evaluated in nesfatin-1 chronically treated rats. The results showed that both acute and chronic administration of nesfatin-1 increased immobility in the forced swimming test (FST), and resulted in the hyperactivity of HPA axis, as indicated by the increase of plasma corticosterone concentration and hypothalamic expression of corticotropin-releasing hormone (CRH) mRNA. Moreover, after chronic nesfatin-1 administration, the rats exhibited decreased activity and exploratory behavior in the open field test (OFT) and increased mRNA expression of synapsin I and synaptotagmin I in the hypothalamus. Furthermore, chronic administration of nesfatin-1 elevated plasma concentrations of IL-6 and CRP, which were positively correlated with despair behavior, plasma corticosterone level, and the hypothalamic mRNA expression of synapsin I and synaptotagmin I. These results indicated that exogenous nesfatin-1 could induce the immune-inflammatory activation, which might be a central hug linking the depression-like behavior and the imbalanced mRNA expression of synaptic vesicle proteins in the hypothalamus.
抑郁症是一种多因素导致的疾病，与代谢调节和免疫炎症反应有关。厌食分子Nesfatin-1最近被认为是一种潜在的情绪调节因子，但其对抑郁症的确切作用及可能机制尚不清楚，尤其是外周给药时。在本研究中，将Nesfatin-1腹腔注射到大鼠体内，评估其抑郁样行为及下丘脑-垂体-肾上腺（HPA）轴的活性。检测了长期接受Nesfatin-1治疗的大鼠血浆中Nesfatin-1、白细胞介素6（IL-6）和C反应蛋白（CRP）的浓度；以及下丘脑Nesfatin-1、突触素I和突触结合蛋白I mRNA的表达水平。结果显示，急性和慢性给予Nesfatin-1均增加了强迫游泳试验（FST）中的不动时间，并导致HPA轴活性增强，表现为血浆皮质酮浓度升高及下丘脑促肾上腺皮质激素释放激素（CRH）mRNA表达增加。此外，慢性给予Nesfatin-1后，大鼠在旷场试验（OFT）中的活动和探索行为减少，下丘脑突触素I和突触结合蛋白I的mRNA表达增加。此外，长期给予Nesfatin-1可使血浆IL-6和CRP浓度升高，这与绝望行为、血浆皮质酮水平以及下丘脑突触素I和突触结合蛋白I的mRNA表达呈正相关。这些结果表明，外源性Nesfatin-1可诱导免疫炎症激活，这可能是连接抑郁样行为与下丘脑突触囊泡蛋白mRNA表达失衡的关键环节。
