Comparison of Two MPTP Doses on Mouse Behaviors and Pathologies

ABSTRACT Parkinson's disease (PD), a prevalent neurodegenerative disorder, is characterized by the selective and progressive degeneration of dopaminergic neurons in the substantia nigra pars compacta, the presence of Lewy bodies (LBs) within neurons, and gliosis. The mouse model induced by the neurotoxin 1‐methyl‐4‐phenyl‐1,2,3,6‐tetrahydropyridine (MPTP) is one of the most commonly utilized animal models for PD; however, its ability to accurately replicate the full spectrum of motor and non‐motor symptoms remains contentious. In this study, we employed novel MPTP administration regimens (160 and 240 mg/kg) to examine the behavioral phenotype and pathological alterations induced by MPTP injury, utilizing a combination of behavioral, molecular, and morphological methodologies. Our findings indicate that MPTP‐induced subacute PD mice exhibited a significant loss of dopaminergic neurons in the ventral midbrain, accompanied by diffuse astrogliosis and activated microglia. Nonetheless, these mice did not display other prominent movement disorders or mood abnormalities, aside from the gait disturbances associated with the administered MPTP dose. Consequently, we propose that the MPTP‐induced subacute PD mouse model utilized in this study represents an early preclinical stage analogous to that observed in human PD patients.