The peroxisome proliferator-activated receptor-γ (PPARγ) coactivator 1α (PGC-1α) is a key regulator of mitochondrial biogenesis, respiration and adaptive thermogenesis. Beside 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). The achievement of neuroprotection via the CNS-targeted pharmacological stimulation is limited due to the poor penetration of the blood brain barrier (BBB) by the proposed pharmaceutical agents, so preconditioning emerged as another option. The current study aimed at the examination 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 the chronic low dose treatment for preconditioning. Ninety minutes following the acute treatment regimen, the expression level of FL-, NT-and CNS-PGC-1α isoforms increased significantly in the striatum, cortex and cerebellum. However, this elevation was diminished 7 days following the last MPTP injection in this acute treatment regimen. The chronic low dose administration of MPTP, which did not cause significant toxic effect in light of the relatively unaltered dopamine levels, neither resulted in any significant change of PGC-1α expression as well. The elevation of PGC-1α levels following acute treatment may demonstrate a short-term compensatory mechanism against the 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.

The aging process clearly increases the demand for antioxidant protection, especially in the brain, involving that provided by α-tocopherol (αT). However, little is known about the age-related changes in brain αT levels and the influencing effect of gender on it, in human or murine samples as well. Accordingly, the aim of the current study was to detect age-, gender- and region-specific changes in αT concentrations in mouse brain tissue and to assess the influencing effect of plasma αT levels on it. Female and male C57BL/6 mice at the ages of 6, 16 and 66 weeks (n = 9 in each group) were applied. αT levels were determined with high performance liquid chromatography (HPLC) from the striatum, cortex, hippocampus, cerebellum, brainstem and from plasma samples. A detailed validation process was carried out for the applied HPLC method as well. The results demonstrated that brain αT levels significantly increased in the striatum, cortex, and hippocampus with aging in both genders, but in a more pronounced way in females with an increasing magnitude of this difference. In case of the cerebellum, a moderate elevation could be detected only in females, whereas in case of the brainstem there was no significant change in αT level. With regard to plasma samples, no clear trend could be identified. The current study is the first to present age-dependent gender-specific changes in αT level in certain brain regions of the C57Bl/6 mouse strain, and may provide meaningful information for future therapeutic studies targeting aging-related processes.

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Huntington's disease is an autosomal dominant progressive neurodegenerative disease, which results in a decreased quality of life and an early death. A high prevalence of vitamin D deficiency was first described in a 2013 study in patients with manifest Huntington's disease, where serum vitamin D level was found to be associated with motor capabilities of the patients. Objectives: Our objective was to investigate the effect of a high-dose vitamin D3 supplementation on a transgenic mouse model of Huntington's disease. Methods: Our study was performed on N171-82Q Huntington's disease transgenic mice in age-and gender-matched groups. We collected data on the motor state and survival of the mice. Results: The results demonstrate that though vitamin D3 had no effect on the motor performance

BackgroundMitochondrial 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. MethodsWe 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. ResultsAdministration 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. ConclusionThese 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.