Wang Sisi, Pan Jiyang
Department of Psychiatry, The First Affiliated Hospital of Jinan University, Guangzhou 510630, China.
Department of Psychiatry, The First Affiliated Hospital of Jinan University, Guangzhou 510630, China.
Biochem Biophys Res Commun. 2016 May 20;474(1):22-28. doi: 10.1016/j.bbrc.2016.04.047. Epub 2016 Apr 11.
Depression is a common psychiatric disorder that affects millions of people around the world, however, little is known about the pathophysiology of depression and the therapeutic strategy for anti-depression. In this study, we investigated the role of irisin, a regulator of energy metabolism, in the modulation of depressive-like behaviors in chronic unpredictable stress (CUS) exposed rats. ELISA showed that irisin was aberrantly regulated by CUS in the prefrontal cortex tissues and cerebrospinal fluid (CSF) of rats. CUS-induced behavioral deficits in rats were reversed by injection treatment with recombinant irisin in a dose dependent manner. Treatment with irisin at concentrations of 100 ng/ml or higher significantly increased the sucrose preference and reduced the immobility time in CUS rats. Additionally, irisin treatment also increased the activities of mitochondrial complexes I, II and IV as well as creatine kinase, which were inhibited by CUS in the prefrontal cortex of rats. We then confirmed that irisin significantly increased the levels of glucose transport and phosphorylation, as reflected by the increased type I and type II hexokinase (Hx-1 and Hx-2) and GLUT-4 as well as the ATP level in vivo and vitro. Further studies indicated that AMPK pathway was involved in the regulation of irisin on depressive-like behaviors in CUS rats. In conclusion, we demonstrated that irisin has a crucial role in inducing antidepressant-like effects in CUS rats by regulating energy metabolism in the prefrontal cortex of brain, which may provide a new insight into the biological mechanism of depression.
抑郁症是一种常见的精神障碍，影响着全球数百万人，然而，人们对抑郁症的病理生理学和抗抑郁治疗策略知之甚少。在本研究中，我们调查了能量代谢调节剂鸢尾素在慢性不可预测应激（CUS）暴露大鼠中对抑郁样行为的调节作用。酶联免疫吸附测定（ELISA）显示，鸢尾素在大鼠前额叶皮质组织和脑脊液（CSF）中受到CUS的异常调节。重组鸢尾素注射治疗以剂量依赖性方式逆转了CUS诱导的大鼠行为缺陷。以100 ng/ml或更高浓度的鸢尾素治疗显著增加了CUS大鼠的蔗糖偏好并减少了不动时间。此外，鸢尾素治疗还增加了线粒体复合物I、II和IV以及肌酸激酶的活性，这些在大鼠前额叶皮质中受到CUS的抑制。然后我们证实，鸢尾素显著增加了葡萄糖转运和磷酸化水平，这在体内和体外表现为I型和II型己糖激酶（Hx-1和Hx-2）、葡萄糖转运蛋白4（GLUT-4）以及ATP水平的增加。进一步的研究表明，AMPK通路参与了鸢尾素对CUS大鼠抑郁样行为的调节。总之，我们证明了鸢尾素通过调节大脑前额叶皮质的能量代谢在CUS大鼠中诱导抗抑郁样作用方面具有关键作用，这可能为抑郁症的生物学机制提供新的见解。
