Neuroprotective effect of fasudil on inflammation through PI3K/Akt and Wnt/β-catenin dependent pathways in a mice model of Parkinson's disease.

Abstract

OBJECTIVE Fasudil, a Rho kinase inhibitor, has neuroprotection in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-based Parkinson's disease (PD). This study aims to investigate the mechanism underlying the neuroprotection of fasudil in the PD mice model. METHODS Female MPTP-intoxication C57BL/6 mice were treated with normal saline or fasudil on day 15 after first administration of MPTP. Pole test was used for the behavioral analysis of mice. Expression of interleukin-1β (IL-1β) and tumor necrosis factor alpha (TNF-α) in brain tissue were detected by ELISA. Expression of tyrosine hydroxylase (TH), p-MYPT1, p-nuclear transcription factor NF-κB, toll-like receptor 2 (TLR2), arginase1, inducible nitric oxide synthase (iNOS), bromodeoxyuridine (BrdU), glial cell line-derived neurotrophic factor (GDNF), p-GSK-3b, p110-PI3K, p-Akt, WNT1, Fzd1 and β-catenin were determined by western blot and immunofluorescence analysis. RESULTS Fasudil enhanced the number of TH neurons which was decreased by MPTP treatment. Behavioral test showed that the motor performance of mice was improved after fasudil treatment. The expression of IL-1β, TNF-α, TLR2 and p-NF-κB and iNOS were lower after fasudil treatment (P<0.05) while the expression of arginase1 was increased (P<0.05). Further, we could observe the increase of GDNF expression in the microglial cells. The expression of p110-PI3K, p-Akt, WNT1, Fzd1 and β-catenin were increased after fasudil administration (P<0.05) in MPTP-based mice model. CONCLUSIONS Maybe fasudil protect dopamine neurons from loss in the MPTP mice model of PD through inflammatory inhibition via activation of PI3K/p-Akt and WNT1/Fzd1/β-catenin cell signaling pathways.

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@article{Zhao2015NeuroprotectiveEO, title={Neuroprotective effect of fasudil on inflammation through PI3K/Akt and Wnt/β-catenin dependent pathways in a mice model of Parkinson's disease.}, author={Yongfei Zhao and Qiong Zhang and Jianying Xi and Baoguo Xiao and Yanhua Li and Cun-gen Ma}, journal={International journal of clinical and experimental pathology}, year={2015}, volume={8 3}, pages={2354-64} }