[Effect of electroacupuncture on the permeability of blood-brain-barrier mediated by Wnt7a/β-catenin/GSK-3β pathway in mice with Parkinson's disease].
[Effect of electroacupuncture on the permeability of blood-brain-barrier mediated by Wnt7a/β-catenin/GSK-3β pathway in mice with Parkinson's disease].
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Original abstract
OBJECTIVES: To observe the effect of electroacupuncture (EA) on the permeability of blood-brain-barrier (BBB) and the regulation of the wingless-type mouse mammary tumor virus integration site 7a (Wnt7a)/β-catenin/glycogen synthase kinase-3β (GSK-3β) pathway in Parkinson's disease (PD) mice. METHODS: Thirty C57 BL/6 mice were randomly divided into normal, model and EA groups, with 10 mice in each group. The PD model was established by intraperitoneal injection of 1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine (MPTP, 30 mg/kg), once daily for 7 days. In the EA group, acupuncture was applied to "Fengfu"(GV16), EA was applied to bilateral "Taichong"(LR3) and "Zusanli"(ST36) for 30 min, once daily for 7 days. The autonomic motor activity of mice in each group were observed by open-field test. The expression of tyrosine hydroxylase (TH) in substantia nigra was determined by immunohistochemistry. The permeability of BBB was detected by Evans blue staining. The expressions of Zona Occludens 1 (ZO-1), Occludin, Claudin-5, Wnt7a, β-catenin and p-GSK-3β in substantia nigra were detected by Western blot. The positive cell expression of Wnt7a in substantia nigra was detected by immunofluorescence. RESULTS: Compared with the normal group, the behavioural score was increased (P<0.01), the total time of autonomic movement, the total distance and the average speed were decreased (P<0.01), the expression of TH in substantia nigra, the protein expressions of ZO-1, Occludin, Claudin-5, Wnt7a, β-catenin were down-regulated (P<0.01), the positive cell rate of Wnt7a was decreased (P<0.01) in the model group, while p-GSK-3β protein express and the content of Evans blue was increased (P<0.01). After EA intervention and compared with the model group, the behavioural score was decreased (P<0.01), the total time of autonomic movement, the total distance and the average speed were increased (P<0.01), the expressions of TH, ZO-1, Occludin, Claudin-5, Wnt7a and β-catenin were all up-regulated (P<0.01), the positive cell rate of Wnt7a was increased (P<0.01), while p-GSK-3β protein express and the content of Evans blue was decreased (P<0.01) in the EA group. CONCLUSIONS: EA can effectively improve the motor dysfunction of PD mice, reduce the damage of dopaminergic neurons, and play a neuroprotective role. These effects may be associated with the up-regulation of tight junction proteins ZO-1, Occludin and Claudin-5, the regulation of key proteins in the Wnt7a / β-catenin / GSK-3β pathway, and the improvement of BBB permeability.