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Proper mitochondrial function is crucial for intact cellular homeostasis. Mitochondrial dysfunction is clearly involved in the pathogenesis of most neurodegenerative- and age-related chronic disorders. The aim of this study is to stimulate cellular production of important compounds of mitochondrial biogenesis, namely in the peroxisome proliferator-activated receptor-gamma coactivator (PGC)- and Sirtuin (SIRT)-systems. We studied the effect of cold challenge and training on the mRNA expression levels of some compounds of these systems in different brain areas of mice. With regard to the PGC-system, the mRNA levels of the full- and N-truncated isoforms, and those of the two promoters (brain-specific, reference) were measured. In case of Sirtuins, the mRNA levels of SIRT1 and SIRT3-M1/M2/M3 were assessed. We found the following expression level alterations: cooling resulted in the elevation of cortical SIRT3-M1 levels and the decrease of cerebellar SIRT3-M3 levels after 200 min. 900 min of cold exposure resulted in the reduction of cortical SIRT1 and striatal SIRT3-M1 levels. A prominent elevation could be observed in the levels of all PGC-1α isoforms in the cerebellum after 12 days of training. The 12 days of exercise resulted in increased cerebellar SIRT3-M1 and SIRT3-M2 mRNA levels as well. Although the efficacy of cooling core body and brain temperature is questionable, we found that training exerted a clear effect. The cause of the prominent cerebellar elevation of PGC-, and Sirtuin isoforms could be an increase in synaptic plasticity between Purkinje cells, which facilitates better motor coordination and more precise movement integration. We propose that these systems may serve as promising targets for future therapeutic studies in neurodegenerative diseases., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Corroborating with prior experimental findings, we recently reported the pronounced elevation of peroxisome proliferator-activated receptor gamma (PPARγ) protein concentration in the cerebrospinal fluid (CSF) of patients with multiple sclerosis (MS), in association with neuroinflammatory markers and clinical severity. Based on subsequent reports on the possible involvement of other PPARs and PPARγ coactivator-1alpha (PGC-1α) in neuroinflammation in MS, we analyzed the protein levels of PPARα, PPARβ/δ, and PGC-1α in a subset of CSF samples from the same cohort of relapsing-remitting MS patients. Unlike PPARγ, none of these proteins were found elevated in MS patients (n=25) compared to non-inflammatory controls (n=16), with the levels of PPARα and PPARβ/δ found generally below the limit of detection, and that of PGC-1α being detectable but comparable in both groups. The clinical and laboratory associations previously reported with PPARγ were however significant even in this smaller subset. The potential underlying causes of these differential alterations are discussed. The findings suggest that despite their proposed involvement in the regulation of inflammatory processes in MS, PPARα, PPARβ/δ, and PGC-1α proteins are not potential biomarkers of neuroinflammation in MS, and indicate a preferential role of PPARγ in the endogenous regulation of autoimmune response in the human CNS within its receptor family., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Peroxisome proliferator-activated receptor gamma (PPARγ), a ligand-activated transcriptional factor involved in the regulation of glucose and lipid metabolism, has gained interest as a potential therapeutic target in multiple sclerosis (MS) due to its potent immunoregulatory properties and the therapeutic efficacy of its ligands in experimental autoimmune encephalitis (EAE). Elevated expression of PPARγ has been observed in the spinal cord of EAE mice and in an in vitro model of antigen-induced demyelination; however, no reports have yet been available on the PPARγ status in the central nervous system of human individuals with MS. Aiming to identify a possible alteration, the present study assessed the levels of PPARγ protein in the cerebrospinal fluid (CSF) of MS patients via ELISA technique. We report a pronounced elevation in the CSF levels of PPARγ in MS patients (n=35) compared to non-inflammatory controls (n=22). This elevation was independent of blood-CSF barrier integrity, but correlated with CSF white blood cell count and IgG index, associating the observed elevation with neuroinflammation. Controlling for potential confounders, the CSF levels of PPARγ further displayed a moderate but significant association with clinical severity. Corroborating with prior experimental findings, these results may contribute to our understanding about the role of PPARγ in MS, and may implicate this protein as a potential CSF biomarker of the disease., (Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.)

Vitamin D receptor (VDR) gene encodes a transcription factor that influences calcium homeostasis and immunoregulation, and may play a role in neurological disorders including Parkinson's disease (PD). The investigations of the association between VDR and PD in different populations revealed various results. In a present study 100 PD patients and 109 healthy controls from the Hungarian population were genotyped for four polymorphic sites (BsmI, ApaI, FokI and TaqI) in the VDR gene. The polymorphisms were determined by polymerase chain reaction and restriction fragment length polymorphism (PCR-RFLP). Our results demonstrate an association between the FokI C allele and PD; the frequency of the C allele was significantly higher in PD patients than in controls, suggesting that this polymorphism may have a role in the development of PD in these patients., (Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.)