RGD Reference Report - Localization of the transcriptional coactivator PGC-1alpha to GABAergic neurons during maturation of the rat brain. - Rat Genome Database

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Localization of the transcriptional coactivator PGC-1alpha to GABAergic neurons during maturation of the rat brain.

Authors: Cowell, RM  Blake, KR  Russell, JW 
Citation: Cowell RM, etal., J Comp Neurol. 2007 May 1;502(1):1-18.
RGD ID: 10059646
Pubmed: (View Article at PubMed) PMID:17335037
DOI: Full-text: DOI:10.1002/cne.21211

The transcriptional coactivator peroxisome proliferator activated receptor gamma coactivator 1alpha (PGC-1alpha) can activate a number of transcription factors to regulate mitochondrial biogenesis and cell-specific responses to cold, fasting, and exercise. Recent studies indicate that PGC-1alpha knockout mice exhibit behavioral abnormalities and progressive vacuolization in various brain regions. To investigate the roles for PGC-1alpha in the nervous system, we evaluated the temporal and cell-specific expression of PGC-1alpha in the normal developing rat brain. Western blot of whole brain homogenates with a PGC-1alpha-specific antibody revealed that PGC-1alpha protein was most abundant in the embryonic and early postnatal forebrain and cerebellum. Using quantitative reverse-transcriptase polymerase chain reaction (RT-PCR), we determined that PGC-1alpha mRNA expression increased most markedly between postnatal days 3 (P3) and 14 in the cortex, striatum, and hippocampus. Immunohistochemical and immunofluorescence analyses of brain tissue indicated that while PGC-1alpha was found in most neuronal populations from embryonic day 15 to P3, it was specifically concentrated in GABAergic populations from P3 to adulthood. Interestingly, PGC-1alpha colocalized with the developmentally regulated chemoattractant reelin in the cortex and hippocampus, and the survival-promoting transcription factor myocyte enhancing factor 2 was highly concentrated in GABAergic populations in the striatum and cerebellum at times of PGC-1alpha expression. These results implicate PGC-1alpha as a regulator of metabolism and/or survival in GABAergic neurons during a phase of mitochondrial and synaptic changes in the developing brain and suggest that PGC-1alpha may be a good target for increasing metabolism in GABAergic populations in neurodevelopmental and neurodegenerative disorders.

Annotation

Gene Ontology Annotations    

Biological Process

Cellular Component

Objects Annotated

Genes (Rattus norvegicus)
Ppargc1a  (PPARG coactivator 1 alpha)


Additional Information