Effect of electroacupuncture on regulation of the basic fibroblast growth factor/glycogen synthase kinase-3β pathway in Parkinson's disease mice.

Abstract

Objectives: To observe the effect of electroacupuncture (EA) on basic fibroblast growth factor (BFGF)/glycogen synthase kinase-3β (GSK-3β) pathway in Parkinson's disease (PD) mice, so as to explore the potential mechanisms of EA in treating PD.

Methods: Fifty C57/BL6 male mice were randomly divided into the control, model, EA, inhibitor and EA+inhibitor (combination) groups, with 10 mice in each group. The PD mouse model was established by intraperitoneal injection of 1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine. Mice in the EA group received EA stimulation at "Fengfu" (GV16), "Taichong"(LR3) and "Zusanli"(ST36) for 30 min, once daily for 12 days. The inhibitor group received gavage of fibroblast growth factor receptor (FGFR) inhibitor AZD4547 (12.5 mg·kg^-1·d^-1) for 12 consecutive days. The open box experiment was used to observe the autonomous movement ability of mice. The expression level of tyrosine hydroxylase (TH) in substantia nigra was detected by immunohistochemistry. The apoptosis rate of substantia nigra cells was measured by TUNEL method. The relative protein expression levels of BFGF, phosphorylated phosphatidylinositol 3-kinase (p-PI3K), phosphorylated protein kinase B (p-AKT), p-GSK-3β, B-lymphomatoma-2 gene (Bcl-2), and Bcl associated X protein (Bax) in substantia nigra were detected by Western blot.

Results: After modeling, compared with the control group, the total movement distance was shorten and the duration of rest was prolonged in the open box experiment (P<0.01), the average absorbance of TH in the substantia nigra of the midbrain was decreased (P<0.01), and the apoptosis rate of substantia nigra cells in the midbrain was increased (P<0.01), the protein expression levels of BFGF, p-PI3K, p-AKT, p-GSK-3β and Bcl-2 were decreased (P<0.01), while the expression level of Bax protein was increased (P<0.01) in the model group. Compared with the model and the combination groups, the total movement distance was prolonged and the duration of rest was shorten (P<0.01), the average absorbance of TH was increased (P<0.05), and the apoptosis rate was decreased (P<0.01, P<0.05), the expression levels of BFGF, p-PI3K, p-AKT, p-GSK-3β and Bcl-2 were increased (P<0.01, P<0.05), while the expression level of Bax was decreased (P<0.05) in the EA group.

Conclusions: EA at GV16, LR3 and ST36 can alleviate motor disorders, reduce cell apoptosis, protect dopaminergic neurons in mice with PD, which may be related to its effect in regulating the BFGF/GSK-3β pathway.