Journal
BRAIN RESEARCH
Volume 1660, Issue -, Pages 20-26Publisher
ELSEVIER SCIENCE BV
DOI: 10.1016/j.brainres.2017.01.032
Keywords
FL-PGC-1 alpha; NT-PGC-1 alpha; CNS-PGC-1 alpha; MPTP; Preconditioning; Dopamine
Categories
Funding
- Hungarian Brain Research Program [KTIA_13_NAP-A-II/18]
- MTA-SZTE Neuroscience Research Group
- Hungarian Academy of Sciences
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The peroxisome proliferator-activated receptor-gamma (PPAR gamma) coactivator 1 alpha (PGC-1 alpha) is a key regulator of mitochondrial biogenesis, respiration and adaptive thermogenesis. Besides the full-length protein (FLPGC-1 alpha), several other functionally active PGC-la isoforms were identified as a result of alternative splicing (e.g., N-truncated PGC-1 alpha; NT-PGC-1 alpha) or alternative promoter usage (e.g., central nervous system specific PGC-1 alpha isoforms; CNS-PGC-1 alpha). 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-1 alpha 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-la 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-1 alpha expression. The elevation of PGC-1 alpha 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-1 alpha system. (C) 2017 Elsevier B.V. All rights reserved.
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