Electroacupuncture Pretreatment Ameliorates PTSD-Like Behaviors in Rats by Enhancing Hippocampal Neurogenesis via the Keap1/Nrf2 Antioxidant Signaling Pathway

被引:35
作者
Zhou, Cui-hong [1 ]
Xue, Fen [1 ]
Xue, Shan-shan [1 ]
Sang, Han-fei [2 ]
Liu, Ling [3 ]
Wang, Ying [1 ]
Cai, Min [1 ]
Zhang, Zhang-Jin [4 ]
Tan, Qing-rong [1 ]
Wang, Hua-ning [1 ]
Peng, Zheng-wu [1 ]
机构
[1] Fourth Mil Med Univ, Xijing Hosp, Xian, Shaanxi, Peoples R China
[2] Xiangan Hosp, Dept Anesthesiol, Xiamen, Fujian, Peoples R China
[3] Fourth Mil Med Univ, Inst Neurosci, Xian, Shaanxi, Peoples R China
[4] Univ Hong Kong, Sch Chinese Med, LKS Fac Med, Hong Kong, Peoples R China
基金
中国国家自然科学基金;
关键词
electroacupuncture; pretreatment; post-traumatic stress disorder; hippocampus; keap1/Nrf2; POSTTRAUMATIC-STRESS-DISORDER; NEURAL STEM-CELLS; OXIDATIVE STRESS; ANXIETY-LIKE; MICROGLIAL ACTIVATION; COGNITIVE IMPAIRMENT; DORSOVENTRAL AXIS; MODEL; NRF2; ACUPUNCTURE;
D O I
10.3389/fncel.2019.00275
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
Electroacupuncture (EA) pretreatment is a clinically useful therapy for several brain disorders. However, whether and via which exact molecular mechanisms it ameliorates post-traumatic stress disorder (PTSD) remains unclear. In the present study, rats received EA stimulation for seven consecutive days before exposure to enhanced single prolonged stress (ESPS). Anxiety-like and fear learning behaviors; hippocampal neurogenesis; the expression of nuclear factor erythroid 2-related factor 2 (Nrf2), Kelch-like ECH-associated protein 1 (keap1), and heme oxygenase 1 (HO-1); and the activity of AMP-activated kinase (AMPK) were evaluated at 14 days after ESPS. EA pretreatment improved hippocampal neurogenesis and ameliorated anxiety-like behaviors in ESPS-treated rats. EA pretreatment also increased the expression of Nrf2 and HO-1 and the activity of AMPK. Furthermore, Nrf2 knockdown by a short hairpin RNA affected anxiety-like behaviors and expression of neuroprotective markers (BDNF, DCX) in a manner similar to ESPS alone and dampened the neuroprotective effects of EA pretreatment. In contrast, Keap1 knockdown increased the expression of HO-1, improved hippocampal neurogenesis, and alleviated PTSD-like behaviors. Altogether, our results suggest that EA pretreatment ameliorates ESPS-induced anxiety-like behaviors and prevents hippocampal neurogenesis disruption in a rat model of PTSD possibly through regulation of the keap1/Nrf2 antioxidant defense pathway.
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页数:16
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