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

Haisong Jiang, SungUng 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 Dawson, Ted M Dawson

Research output: Contribution to journalArticle

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

  • Medicine(all)

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