Abstract
Background: Abundant microglial reaction and neuroinflammation are typical pathogenetic hallmark of brains in Parkinson’s disease (PD) patients, but regulation mechanisms are poorly understood. In this study, the promoting effects of PD-1-difficiency on microglial activation, neuroinflammation and motor dysfunction were identified using PD animal model.Methods: Using C57 wild-type (WT), PD-1 knockout (KO) and MPTP model, we designed WT-control, KO-control, WT-MPTP and KO-MPTP groups. Motor dysfunction of animal, distribution of PD-1-positive cells, dopaminergic neuronal survival, glial cell activation and generation of inflammatory cytokines in midbrains were observed by behavior detection, immunohistochemistry and western blot methods. Results: Microglial cells showing PD-1/Iba1 double-positivity were numerously distributed in the substantia nigra of control whereas they decreased in MPTP model. Compared with WT-MPTP, KO-MPTP mice exacerbated in their motor dysfunction, decreased level of TH expression and decreased TH-positive neuronal protrusions. Microglial cell activation and expression of proinflammatory cytokine iNOS, TNF-α, IL-1β and IL-6 significantly increased, and levels and phosphorylation of AKT and ERK1/2 were also elevated in KO-MPTP mice. Conclusions: PD-1 knockout could aggravate motor dysfunction of MPTP mouse model by promoting microglial activation and neuroinflammation in midbrains, suggesting that PD-1 signaling abnormality might be involved in PD pathogenesis or progression.
Nigral injection of a proteasomal inhibitor, lactacystin, induces widespread glial cell activation and shows various phenotypes of Parkinson’s disease in young and adult mouse
