Min Xiao - College of Acupuncture and Orthopedics, Hubei University of Chinese Medicine, Wuhan, Hubei, China
Xue-Song Wang - School of Acupuncture-Moxibustion and Tuina, Hebei University of Chinese Medicine, Shijiazhuang, Hebei, China
Chuan He - College of Acupuncture and Orthopedics, Hubei University of Chinese Medicine, Wuhan, Hubei, China
Zhong-Sheng Huang - College of Acupuncture and Orthopedics, Hubei University of Chinese Medicine, Wuhan, Hubei, China
Hong-Ru Chen - College of Acupuncture and Orthopedics, Hubei University of Chinese Medicine, Wuhan, Hubei, China
Li-Hong Kong - College of Acupuncture and Orthopedics, Hubei University of Chinese Medicine, Wuhan, Hubei, China

Objective(s): To examine the effect and potential mechanism of electroacupuncture (EA) pretreatment in spatial learning, memory, gut microbiota, and JNK signaling in D-galactose-induced AD-like rats. Materials and Methods: The AD-like rat model was generated by intraperitoneal injection of D-galactose. Morris water maze was used to determine spatial learning and memory ability, Real-time PCR to determine intestinal flora levels, ELISA to determine tryptophan (Trp) and ۵-HT levels in the colon and hippocampal tissues, immunofluorescence to determine ۵-HT levels in enterochromaffin cells (ECs), and immunoblotting to determine JNK signaling protein levels in hippocampal tissues.Results: Electroacupuncture pretreatment significantly reduced escape latency and prolonged exploration time in the target quadrant, and significantly increased the relative DNA abundance of Lactobacillus and Bifidobacterium. Meanwhile, electroacupuncture pretreatment also reduced colonic ۵-HT levels and increased hippocampal ۵-HT levels. Moreover, electroacupuncture pretreatment significantly inhibited hippocampal JNK pathway-related protein expression, including ۵-HT۶R, JNK, p-JUNK, c-JUN, and p-c-Jun. And the combination of GV۲۰ and ST۳۶ was more effective than single acupoints.Conclusion: Electroacupuncture pretreatment improved the learning and memory ability of D-galactose-induced AD-like model rats, changed the gut microbiota composition, and the mechanism may be related to the gut-brain axis and the JNK signaling pathway.   In addition, the combination of GV۲۰ and ST۳۶ could further enhance the efficacy.

۵-HT, ۵-HT۶, Alzheimer’s disease, Brain-gut axis, Electroacupuncture - pretreatment, Gut microbiota, JNK signaling