Effect of MPTP on mRNA expression of PGC-1α in mouse brain

Rita Torok, Andras Salamon, Evelin Sumegi, Denes Zadori, G. Veres, Mate Fort Molnar, L. Vécsei, Peter Klivenyi

Research output: Contribution to journalArticle

5 Citations (Scopus)

Abstract

The peroxisome proliferator-activated receptor-γ (PPARγ) coactivator 1α (PGC-1α) is a key regulator of mitochondrial biogenesis, respiration and adaptive thermogenesis. Besides the full-length protein (FL-PGC-1α), several other functionally active PGC-1α isoforms were identified as a result of alternative splicing (e.g., N-truncated PGC-1α; NT-PGC-1α) or alternative promoter usage (e.g., central nervous system-specific PGC-1α isoforms; CNS-PGC-1α). Achieving neuroprotection via CNS-targeted pharmacological stimulation is limited due to poor penetration of the blood brain barrier (BBB) by the proposed pharmaceutical agents, so preconditioning emerged as another option. The current study aimed to examine of how the expression levels of FL-, NT-, CNS- and reference PGC-1α isoforms change in different brain regions following various 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) treatment regimens, including chronic low-dose treatment for preconditioning. Ninety minutes following the acute treatment regimen, the expression levels of FL-, NT- and CNS-PGC-1α isoforms increased significantly in the striatum, cortex and cerebellum. However, this elevation diminished 7 days following the last MPTP injection in the acute treatment regimen. The chronic low-dose administration of MPTP, which did not cause significant toxic effects in light of the relatively unaltered dopamine levels, did not result in any significant change of PGC-1α expression. The elevation of PGC-1α levels following acute treatment may demonstrate a short-term compensatory mechanism against mitochondrial damage induced by the complex I inhibitor MPTP. However, drug-induced preconditioning by chronic low-dose MPTP seems not to induce protective responses via the PGC-1α system.

Original languageEnglish
Pages (from-to)20-26
Number of pages7
JournalBrain Research
Volume1660
DOIs
Publication statusPublished - Apr 1 2017

Keywords

  • CNS-PGC-1α
  • Dopamine
  • FL-PGC-1α
  • MPTP
  • NT-PGC-1α
  • Preconditioning

ASJC Scopus subject areas

  • Neuroscience(all)
  • Molecular Biology
  • Developmental Biology
  • Clinical Neurology

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    Torok, R., Salamon, A., Sumegi, E., Zadori, D., Veres, G., Molnar, M. F., Vécsei, L., & Klivenyi, P. (2017). Effect of MPTP on mRNA expression of PGC-1α in mouse brain. Brain Research, 1660, 20-26. https://doi.org/10.1016/j.brainres.2017.01.032