TREADMILL EXERCISE PRODUCES NEUROPROTECTIVE EFFECTS IN A MURINE MODEL OF PARKINSON'S DISEASE BY REGULATING THE TLR2/MYD88/NF-kappa B SIGNALING PATHWAY

摘要

Parkinson's disease (PD) is characterized by progressive dopamine depletion and a loss of dopaminergic neurons in the substantia nigra pars compacta (SNpc). Treadmill exercise is a promising non-pharmacological approach for reducing the risk of PD and other neuroinflammatory disorders, such as Alzheimer's disease. The goal of this study was to investigate the effects of treadmill exercise on alpha-synuclein-induced neuroinflammation and neuronal cell death in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced mouse model of PD. Eight weeks of treadmill exercise improved motor deficits and reduced alpha-synuclein expression, a major causative factor of PD-like symptoms, in MPTP mice. Treadmill exercise also down regulated the expression of toll-like receptor 2 and its associated downstream signaling molecules, including myeloid differentiation factor-88, tumor necrosis factor receptor associated factor 6, and transforming growth factor-beta-activated protein kinase 1. These effects were associated with reduced ionized calcium-binding adapter molecule 1 expression, decreased I kappa B alpha and nuclear transcription factor-KB phosphorylation, decreased tumor necrosis factor a and interleukin-1 beta expression, and decreased NADPH oxidase subunit expression in the SNpc and striatum. Additionally, it promoted the expression of tyrosine hydroxylase and the dopamine transporter, as well as plasma dopamine levels, in MPTP mice; these effects were associated with decreased caspase-3 expression and cleavage, as well as increased Bcl-2 expression in the SNpc. Taken together, our data suggest that treadmill exercise improves MPTP-associated motor deficits by exerting neuroprotective effects in the SNpc and striatum, supporting the notion that treadmill exercise is useful as a non-pharmacological tool for the management of PD. (C) 2017 IBRO. Published by Elsevier Ltd. All rights reserved.