Characterization of Age-dependent Behavior Deficits in the PGC-1α Knockout Mouse, in Relevance to the Parkinson's Disease Model.

Neuroscience

Henan Provincial People's Hospital, Cerebrovascular Hospital, Zhengzhou University People's Hospital, Henan University People's Hospital, Zhengzhou, Henan 450003, China. Electronic address:

Published: August 2020

Parkinson's disease is a disorder of adult onset involving the progressive degeneration of selective portions of the central nervous system. It is known that mitochondrial dysfunction is involved in the pathogenesis of PD. Given that PGC-1α induces proliferation of mitochondria via transcription regulation, it is possible that PGC-1α pathway dysregulation is involved in PD pathogenesis. To determine how derangement of the PGC-1α pathway in age contributes to PD, in this study, we have characterized the number of dopaminergic neuron in the substantia nigra pars compacta (SNpc), motor behaviors and related expression of mitochondrial markers (CoxIV, SDHA, and Tomm20) in the ventral midbrains of PGC-1α null mice. We found an overall decrease in spontaneous, voluntary movements and severely impaired motor coordination in all age groups (10 months and 20 months) of PGC-1α null mice, while pole testing detected impaired motor activity in older PGC-1α null mice only. TH-positive neurons were significantly less in older PGC-1α null mice. Concentration of DA as well as its two metabolites reduced in an age-dependent manner in PGC-1α null mice. Expression of CoxIV, SDHA and Tomm20 also significantly decreased in the ventral midbrains of 10-month-old PGC-1α null mice. Thus, PGC-1α KO in mice induced dopaminergic neuron degeneration in the SNpc and DA deficits in the striatum in an age-dependent manner. Progressive impairment of motor coordination in an age-dependent manner was correlated to the extent of nigrostriatal dopaminergic pathway degeneration and mitochondrial dysfunction.

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http://dx.doi.org/10.1016/j.neuroscience.2020.05.015DOI Listing

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