[Effect of electroacupuncture on insulin signaling in the substantia nigra of the midbrain in mice with Parkinson's disease].
[Effect of electroacupuncture on insulin signaling in the substantia nigra of the midbrain in mice with Parkinson's disease].
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Original abstract
OBJECTIVES: To observe the effect of electroacupuncture(EA) at "Fengfu" (GV16), "Taichong" (LR3) and "Zusanli" (ST36) on the behavior and insulin receptor substrate 1 (IRS-1)/phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT) pathway mediated by the insulin-like growth factor 1 receptor (IGF-1R) in the substantia nigra of the midbrain in mice model with Parkinson's disease (PD), so as to explore the mechanism of EA in the prevention and treatment of PD. METHODS: C57BL/6 mice were randomly divided into a control group, a model group, and an EA group, with 10 mice in each group. A PD mouse model was established by intraperitoneal injection of 1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine (MPTP, 30 mg·kg-1·d-1) for 7 consecutive days. The mice in the EA group were given EA at GV16, LR3, and ST36 for 30 min each time, once a day for 12 consecutive days. The open field test was used to observe the behavioral changes of the mice in each group before and after treatment. Immunohistochemistry was used to detect the expression level of tyrosine hydroxylase (TH) in the substantia nigra region of the midbrain. Real-time fluorescence quantitative PCR and Western blot were used to detect the mRNA expression levels of IGF-1R, IRS-1, PI3K, and AKT, and protein expressions of IGF-1R, IRS-1, p-PI3K, and p-AKT in the substantia nigra of the mice, respectively. ELISA was used to detect the contents of tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β) in the substantia nigra of the midbrain. RESULTS: Compared with the control group, mice in the model group showed obvious motor dysfunction. The total distance of spontaneous movement, the average speed, and the duration of movement, the positive expression level of TH in the substantia nigra of the midbrain, and the mRNA expression levels of IGF-1R, PI3K, and AKT, and protein expressions of IGF-1R, p-PI3K/PI3K and p-AKT/AKT ratio in the substantia nigra decreased (P<0.01, P<0.05), while the mRNA and protein expression levels of IRS-1, the contents of the inflammatory factors TNF-α and IL-1β increased (P<0.05, P<0.01). Compared with the model group, all the above indexes of the PD mice after EA treatment were all reversed (P<0.01, P<0.05). CONCLUSIONS: EA at GV16, LR3, and ST36 can effectively improve the bradykinesia of PD model mice induced by MPTP, increase the expression level of TH in the substantia nigra, and improve the insulin signaling dysfunction. Its mechanism may be related to the regulation of the IGF-1R/IRS-1/PI3K/AKT signaling pathway and the subsequent inhibition of the neuroinflammatory response.