Brain Testosterone Deficiency Leads to Down-Regulation of Mitochondrial Gene Expression in Rat Hippocampus Accompanied by a Decline in Peroxisome Proliferator-Activated Receptor-γ Coactivator 1α Expression

Age-related decrease of testosterone levels in blood and brain is believed to be associated with neurodegenerative diseases such as Alzheimer’s disease. However, the effect of testosterone on brain function is not well understood. Therefore, we investigated the impact of testosterone deprivation on...

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Bibliographic Details
Published in:Journal of molecular neuroscience 2014-04, Vol.52 (4), p.531-537
Main Authors: Hioki, Takeshi, Suzuki, Shunya, Morimoto, Megumi, Masaki, Tsuneo, Tozawa, Ryuichi, Morita, Shigeru, Horiguchi, Takashi
Format: Article
Language:English
Subjects:
Aging - physiology
Animals
Biomedical and Life Sciences
Biomedicine
Brain - physiology
Cell Biology
Cerebral Cortex - physiology
Cytochromes b - genetics
Cytochromes b - metabolism
Down-Regulation - drug effects
Down-Regulation - physiology
Electron Transport Complex IV - genetics
Electron Transport Complex IV - metabolism
Genes, Mitochondrial - genetics
Hippocampus - physiology
Humans
Male
Mitochondria - drug effects
Mitochondria - physiology
NADPH Dehydrogenase - genetics
NADPH Dehydrogenase - metabolism
Neurochemistry
Neurology
Neurosciences
Orchiectomy
Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha
Proteomics
Rats
Rats, Sprague-Dawley
Testosterone - deficiency
Testosterone - pharmacology
Transcription Factors - genetics
Transcription Factors - metabolism
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Summary:Age-related decrease of testosterone levels in blood and brain is believed to be associated with neurodegenerative diseases such as Alzheimer’s disease. However, the effect of testosterone on brain function is not well understood. Therefore, we investigated the impact of testosterone deprivation on mitochondrial gene expression in the brain of male gonadectomized (GDX) rats. We found that peripheral castration led to testosterone deficiency in the brain and caused a significant reduction in protein and mRNA expression of genes encoded by mitochondrial DNA, namely NADPH dehydrogenase subunit 1, subunit 4, cytochrome b, and cytochrome c oxidase subunit 1 and subunit 3 in the hippocampus. In addition, gene expression of peroxisome proliferator-activated receptor-γ coactivator 1α (PGC-1α), which is a master regulator of mitochondrial biogenesis, and its downstream transcriptional factors, nuclear respiratory factors 1 and 2 and mitochondrial transcription factors A and B2, were also decreased in the hippocampus of GDX rats. These reductions in the expression of mitochondrial gene and transcriptional coactivators and factors were recovered by androgen replacement. These findings indicate that androgen plays an important role in mitochondrial gene expression in the hippocampus.
ISSN:0895-8696
1559-1166
DOI:10.1007/s12031-013-0108-3