Adult conditional knockout of PGC-1α leads to loss of dopamine neurons

Haisong Jiang, Sung Ung Kang, Shuran Zhang, Senthilkumar Karuppagounder, Jinchong Xu, Yong Kyu Lee, Bong Gu Kang, Yunjong Lee, Jianmin Zhang, Olga Pletnikova, Juan C. Troncoso, Shelia Pirooznia, Shaida A. Andrabi, Valina L. Dawson, Ted M. Dawson

Research output: Contribution to journalArticlepeer-review

Abstract

Parkinson’s disease (PD) is a chronic progressive neurodegenerative disorder. Recent studies have implicated a role for peroxisome proliferator-activated receptor γ coactivator protein-1α (PGC-1α) in PD and in animal or cellular models of PD. The role of PGC-1α 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-1α isoforms expressed in SH-SY5Y cells, and these four isoforms are expressed across subregions of mouse brain. Adult conditional PGC-1α 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-1α isoforms and mitochondria markers. Our findings suggest that all four isoforms of PGC-1α are required for the proper expression of mitochondrial proteins in SNpc DA neurons and that PGC-1α is essential for SNpc DA neuronal survival, possibly through the maintenance of mitochondrial function.

Original languageEnglish (US)
Article numbere0183-16.2016
JournaleNeuro
Volume3
Issue number4
DOIs
StatePublished - 2016

Keywords

  • Dopamine neuron
  • Mitochondria
  • Neurodegeneration
  • PGC-1α
  • Substantia nigra

ASJC Scopus subject areas

  • Neuroscience(all)

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