Background Mitochondrial dysfunction play a significant role in the patomechanism of several neurodegenerative disorders, including Huntington’s disease. PGC-1α is a master regulator of mitochondrial biogenesis, thus it could serve as a potential therapeutic target in these disorders. Due to the several tissue-specific isoforms and the limitation of the blood-brain barrier penetration, the brain specific stimulation of the expression of this transcriptional factor is difficult.
Methods We have used several different paradigms including physical and chemical factors in wild-type mice to stimulate the expression of PGC-1α in certain brain areas affected most in neurodegenerative disorders.
Results Administration of mitochondrial toxin MPTP produce a significant elevation of brain specific as well as full length and NT isoforms in several brain regions. The long term, but not the short term rotarod training produced a moderate, but significant increase of expression of all isoforms exclusively in the cerebellum. However the calorie restriction, the cold challenge or vitamin D administration did not alter the PGC-1α expression in any region of the brain.
Conclusion These data produce evidence that brain specific stimulation of this mitochondrial key regulator is not easily feasible. So further studies are needed with blood-brain barrier penetrating molecules.
This work was supported by grants KTIA_13_NAP-A-II/17 of National Brain Research Program.
- brain-specific expression