AI Article Synopsis
- Fasudil, a Rho kinase inhibitor, shows neuroprotective effects in a Parkinson's disease mouse model, enhancing motor performance and the number of dopamine neurons.
- Treatment with fasudil reduces inflammatory markers like IL-1β and TNF-α, while increasing the expression of neuroprotective factors like arginase1 and GDNF.
- The study suggests that fasudil's protective mechanism may involve the activation of specific cell signaling pathways, including PI3K/p-Akt and WNT1/Fzd1/β-catenin.
Article 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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