[Effect of electroacupuncture on the permeability of blood-brain-barrier mediated by Wnt7a/β-catenin/GSK-3β pathway in mice with Parkinson's disease].

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.