Huang Hui-Jie, Zhu Xiao-Cang, Han Qiu-Qin, Wang Ya-Lin, Yue Na, Wang Jing, Yu Rui, Li Bing, Wu Gen-Cheng, Liu Qiong, Yu Jin
Department of Integrative Medicine and Neurobiology, State Key Lab of Medical Neurobiology, Institutes of Brain Science, Shanghai Medical College, Fudan University, Shanghai 200032, China.
Center Laboratory, Jinshan Hospital of Fudan University, Shanghai 201508, China.
Behav Brain Res. 2017 May 30;326:33-43. doi: 10.1016/j.bbr.2017.02.040. Epub 2017 Feb 27.
As a regulator of food intake, ghrelin also plays a key role in mood disorders. Previous studies reported that acute ghrelin administration defends against depressive symptoms of chronic stress. However, the effects of long-term ghrelin on rodents under chronic stress hasn't been revealed. In this study, we found chronic peripheral administration of ghrelin (5nmol/kg/day for 2 weeks, i.p.) could alleviate anxiety- and depression-like behaviors induced by chronic unpredictable mild stress (CUMS). The depression-like behaviors were assessed by the forced swimming test (FST), and anxiety-like behaviors were assessed by the open field test (OFT) and the elevated plus maze test (EPM). Meanwhile, we observed that peripheral acylated ghrelin, together with gastral and hippocampal ghrelin prepropeptide mRNA level, were significantly up-regulated in CUMS mice. Besides, the increased protein level of growth hormone secretagogue receptor (GHSR) in hippocampus were also detected. These results suggested that the endogenous ghrelin/GHSR pathway activated by CUMS plays a role in homeostasis. Further results showed that central treatment of ghrelin (10μg/rat/day for 2 weeks, i.c.v.) or GHRP-6 (the agonist of GHSR, 10μg/rat/day for 2 weeks, i.c.v.) significantly alleviated the depression-like behaviors induced by CUMS in FST and sucrose preference test (SPT). Based on these results, we concluded that central GHSR is involved in the antidepressant-like effect of exogenous ghrelin treatment, and ghrelin/GHSR may have the inherent neuromodulatory properties against depressive symptoms.
作为食物摄入的调节因子，胃饥饿素在情绪障碍中也起着关键作用。先前的研究报道，急性给予胃饥饿素可抵御慢性应激的抑郁症状。然而，长期胃饥饿素对慢性应激下啮齿动物的影响尚未明确。在本研究中，我们发现慢性外周给予胃饥饿素（5nmol/kg/天，持续2周，腹腔注射）可减轻慢性不可预测温和应激（CUMS）诱导的焦虑样和抑郁样行为。通过强迫游泳试验（FST）评估抑郁样行为，通过旷场试验（OFT）和高架十字迷宫试验（EPM）评估焦虑样行为。同时，我们观察到CUMS小鼠外周酰化胃饥饿素以及胃和海马中胃饥饿素前体肽mRNA水平显著上调。此外，还检测到海马中生长激素促分泌素受体（GHSR）蛋白水平升高。这些结果表明，CUMS激活的内源性胃饥饿素/GHSR通路在体内平衡中起作用。进一步的结果表明，中枢给予胃饥饿素（10μg/大鼠/天，持续2周，脑室内注射）或GHRP - 6（GHSR激动剂，10μg/大鼠/天，持续2周，脑室内注射）可显著减轻FST和蔗糖偏好试验（SPT）中CUMS诱导的抑郁样行为。基于这些结果，我们得出结论，中枢GHSR参与外源性胃饥饿素治疗的抗抑郁样作用，并且胃饥饿素/GHSR可能具有对抗抑郁症状的内在神经调节特性。
