Increased vulnerability with aging to MPTP: the mechanisms underlying mitochondrial dynamics.

Objective: The risk and vulnerability of Parkinson disease (PD) are especially high in the elderly. However, the underlying causes are unknown. 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) mice are useful tools to some extent for investigating PD-related problems due to their PD-like symptoms. The study is aimed to determine whether and what mitochondrial-events during aging are related with the increased vulnerability of the elderly to MPTP. Methods: The MPTP mice were established by intraperitoneal injection of MPTP, control animals were injected with saline. Mice of different ages were divided into six groups: 4-month old control group, 4-month old MPTP group, 8-month old control group, 8-month old MPTP group, 15-month old control group, and 15-month old MPTP group. The behavior ability and pathology were assessed for each mouse. Mitochondrial functions were measured and compared among different groups. Mitochondrial fusion/fission-related proteins and autophagic proteins were analyzed by western blotting. Results: The elder animals were impaired more severely in behavior and pathology than the young ones. Then, we revealed that aging is associated with the degeneration of several mitochondrial functions, disturbed balance of fusion/fission as well as decreased activity of autophagic proteins. More importantly, mitochondria in the elderly are more vulnerable to MPTP treatment than that in the young, which may contribute to the increased risk and vulnerability of the elderly to MPTP. Conclusion: We identified several changes of mitochondrial-events with aging MPTP mice that could be related to the MPTP susceptivity and vulnerability, which would provide significant instructions for future in developing proper interventions that lower the vulnerability, or slow the progression of PD in the elderly.