Adult Conditional Knockout of PGC-1? Leads to Loss of Dopamine Neurons.

ABSTRACT: Parkinson's disease (PD) is a chronic progressive neurodegenerative disorder. Recent studies have implicated a role for peroxisome proliferator-activated receptor ? coactivator protein-1? (PGC-1?) in PD and in animal or cellular models of PD. The role of PGC-1? in the function and survival of substantia nigra pars compacta (SNpc) dopamine neurons is not clear. Here we find that there are four different PGC-1? isoforms expressed in SH-SY5Y cells, and these four isoforms are expressed across subregions of mouse brain. Adult conditional PGC-1? knock-out mice show a significant loss of dopaminergic neurons that is accompanied by a reduction of dopamine in the striatum. In human PD postmortem tissue from the SNpc, there is a reduction of PGC-1? isoforms and mitochondria markers. Our findings suggest that all four isoforms of PGC-1? are required for the proper expression of mitochondrial proteins in SNpc DA neurons and that PGC-1? is essential for SNpc DA neuronal survival, possibly through the maintenance of mitochondrial function.

SUBMITTER: Jiang H 

PROVIDER: S-EPMC5011687 | biostudies-literature | 2016 Jul-Aug

REPOSITORIES: biostudies-literature