Long-term Changes in the Nigrostriatal Pathway in the MPTP Mouse Model of Parkinson's Disease

Parkinson's disease (PD) is a common and progressive neurodegenerative disorder. The 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) mouse model of PD is widely used to study the progression of this disease. Behavior impairment is closely related to the damage of the dopaminergic system in the basal ganglia. Here, MPTP-induced changes in mouse behavior and glial activation were evaluated at different time points after the treatment and the long-term changes in the nigrostriatal pathway were analyzed. We found that mice exposed to MPTP displayed a full recovery in the rotarod test and the pole test but not in the wire hanging test at 65 days post-injection. A biphasic activation of microglial cells was revealed in the nigrostriatal pathway of MPTP-treated mice. However, activation of astrocytes displayed an approximately bell-shaped kinetics and an approximately S-shaped kinetics in the striatum and the substantia nigra, respectively. In addition, the numbers of complement component 3 (C3)-positive neurotoxic astrocytes in the substantia nigra of MPTP-treated mice increased with time and reached a maximum at 42 days, and declined at 74 days, after the treatment. Three months later, the dopaminergic system was partially recovered from the lesion of MPTP. The time course of pathophysiological events has important implications for the interventions or treatment of PD.