Effect of MPTP on mRNA expression of PGC-1α in mouse brain.
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 7days 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.
Department of Neurology, University of Szeged, Semmelweis u. 6, H-6725 Szeged, Hungary.
Rita
R
Torok
Department of Neurology, University of Szeged, Semmelweis u. 6, H-6725 Szeged, Hungary.
Andras
A
Salamon
Department of Neurology, University of Szeged, Semmelweis u. 6, H-6725 Szeged, Hungary.
Evelin
E
Sumegi
Department of Neurology, University of Szeged, Semmelweis u. 6, H-6725 Szeged, Hungary.
Denes
D
Zadori
MTA-SZTE Neuroscience Research Group of the Hungarian Academy of Sciences and University of Szeged, Semmelweis u. 6, H-6725 Szeged, Hungary.
Gabor
G
Veres
Department of Neurology, University of Szeged, Semmelweis u. 6, H-6725 Szeged, Hungary.
Mate Fort
MF
Molnar
Department of Neurology, University of Szeged, Semmelweis u. 6, H-6725 Szeged, Hungary; MTA-SZTE Neuroscience Research Group of the Hungarian Academy of Sciences and University of Szeged, Semmelweis u. 6, H-6725 Szeged, Hungary.
Laszlo
L
Vecsei
Department of Neurology, University of Szeged, Semmelweis u. 6, H-6725 Szeged, Hungary. Electronic address: klivenyi.peter@med.u-szeged.hu.
Peter
P
Klivenyi
D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine / Q000008:administration & dosage*; D015102:3,4-Dihydroxyphenylacetic Acid / Q000378:metabolism; D000818:Animals; D001921:Brain / Q000187:drug effects* / Q000378:metabolism*; D004298:Dopamine / Q000378:metabolism; D015259:Dopamine Agents / Q000008:administration & dosage*; D015870:Gene Expression / Q000187:drug effects; D006719:Homovanillic Acid / Q000378:metabolism; D020267:MPTP Poisoning / Q000378:metabolism; D008297:Male; D008810:Mice, Inbred C57BL; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha / Q000378:metabolism*; D020033:Protein Isoforms / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D011897:Random Allocation; D013997:Time Factors
D015259:Dopamine Agents; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; C485290:Ppargc1a protein, mouse; D020033:Protein Isoforms; D012333:RNA, Messenger; D015102:3,4-Dihydroxyphenylacetic Acid; D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; D004298:Dopamine; D006719:Homovanillic Acid
CNS-PGC-1α; Dopamine; FL-PGC-1α; MPTP; NT-PGC-1α; Preconditioning