Microglial activation contributes to cognitive impairments in rotenone-induced mouse Parkinson’s disease model

Abstract Background Cognitive decline occurs frequently in Parkinson’s disease (PD), which greatly decreases the quality of life patients. However, mechanisms remain to be investigated. Neuroinflammation mediated by overactivated microglia is a common pathological feature multiple neurological disorders, including PD. This study designed explore role cognitive deficits using rotenone-induced mouse PD model. Methods To evaluate deficits, PLX3397, an inhibitor colony-stimulating factor 1 receptor, and minocycline, widely used antibiotic, were deplete or inactivate microglia, respectively. performance mice among groups was detected Morris water maze, objective recognition, passive avoidance tests. Neurodegeneration, synaptic loss, ?-synuclein phosphorylation, glial activation, apoptosis determined immunohistochemistry Western blot immunofluorescence staining. The gene expression inflammatory factors lipid peroxidation further explored RT-PCR ELISA kits, Results Rotenone dose-dependently induced showing decreased rotenone-treated novel avoidance, maze compared with that vehicle controls. Rotenone-induced associated neurodegeneration, Ser129-phosphorylation microglial activation hippocampal cortical regions mice. A time course experiment revealed preceded neurodegeneration. Interestingly, depletion PLX3397 inactivation minocycline significantly reduced neuronal damage pathology as well improved rotenone-injected Mechanistically, attenuated astroglial production cytotoxic Reduced also observed treated combined rotenonee rotenone alone group. Finally, found mitigate apoptosis. Conclusions Taken together, our findings suggested contributes impairments model via neuroinflammation, oxidative stress, apoptosis, providing insight into immunopathogensis