Electro-Acupuncture Alleviates Chronic Unpredictable Stress-Induced Depressive- and Anxiety-Like Behavior and Hippocampal Neuroinflammation in Rat Model of Depression

Na Yue; Bing Li; Liu Yang; Qiu-Qin Han; Hui-Jie Huang; Ya-Lin Wang; Jing Wang; Rui Yu; Gen-Cheng Wu; Qiong Liu; Jin Yu

doi:10.3389/fnmol.2018.00149

Electro-Acupuncture Alleviates Chronic Unpredictable Stress-Induced Depressive- and Anxiety-Like Behavior and Hippocampal Neuroinflammation in Rat Model of Depression

Front Mol Neurosci. 2018 May 31:11:149. doi: 10.3389/fnmol.2018.00149. eCollection 2018.

Authors

Na Yue¹, Bing Li², Liu Yang¹, Qiu-Qin Han¹, Hui-Jie Huang¹, Ya-Lin Wang¹, Jing Wang¹, Rui Yu¹, Gen-Cheng Wu¹, Qiong Liu^{3

4}, Jin Yu¹

Affiliations

¹ Department of Integrative Medicine and Neurobiology, State Key Laboratory of Medical Neurobiology, School of Basic Medical Sciences, Institutes of Brain Science, and Collaborative Innovation Center for Brain Science, Shanghai Medical College, Fudan University, Shanghai, China.
² Center Laboratories, Jinshan Hospital of Fudan University, Shanghai, China.
³ Department of Anatomy, Histology and Embryology, School of Basic Medical Sciences, Shanghai Medical College, Fudan University, Shanghai, China.
⁴ Key Laboratory of Medical Imaging Computing and Computer Assisted Intervention of Shanghai, Shanghai, China.

Abstract

Depression is the second leading cause of disability worldwide. The effects of clinical depression may be mediated by neuroinflammation such as activation of microglia and high levels of proinflammatory cytokines in certain brain areas. Traditional Chinese medicine techniques such as electro-acupuncture (EA) are used extensively in Asia to treat mental health disorders. However, EA has not been rigorously studied in treatment of depression. This study was designed to assess the effectiveness of EA on depressive-like behavior and explore the role of hippocampal neuroinflammation in the potential antidepressant effect of EA. In this study, we used six chronic unpredictable stressors daily in a random sequence for 10 weeks. EA were performed on "Bai-Hui" (Du-20) (+) and "Yang-Ling-Quan" (GB-34, the right side; -) acupoints by an EA apparatus (HANS Electronic Apparatus, LH202H, 2/100 Hz, 0.3 mA) for 30 min once every other day for last 4 weeks. The behavior tests including open field test and forced swimming test, which are widely used to assess depressive and anxiety-like behavior were performed on the Monday and Tuesday of the eleventh week. The results showed that 10 week of chronic unpredictable stress (CUS) caused behavioral deficits in rats and neuroinflammation in hippocampus, such as increased expression of NLRP3 inflammasome components, upregulated mRNA level of IL-1β and the protein level of IL-1β mature form (p17) and activation of microglia. Moreover, 4 weeks of EA treatment significantly attenuated behavioral deficits caused by CUS. EA's antidepressant effect was accompanied by markedly decreased expression of certain NLRP3 inflammasome components and matured IL-1β. Meanwhile, EA treatment can significantly reverse CUS-induced increases in P2X7 receptor, Iba-1, IL-18, TNFα and IL-6 expression and decreases in GFAP expression. In conclusion, EA exhibited the antidepressant effect and alleviated the hippocampal neuroinflammation. These findings may provide insight into the role of hippocampal neuroinflammation in the antidepressant effect of EA.

Keywords: EA; IL-1β; P2X7 receptor; chronic unpredictable stress; depression; glia.