title: Localization of the transcriptional coactivator PGC-1alpha to GABAergic neurons during maturation of the rat brain.
abstract: 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.
authors.affiliation: Department of Psychiatry, University of Alabama, Birmingham, Alabama 35294, USA.
authors.forename: Rita Marie
authors.initials: RM
authors.lastname: Cowell
authors.forename: Kathryn Rose
authors.initials: KR
authors.lastname: Blake
authors.forename: James W
authors.initials: JW
authors.lastname: Russell
mesh_terms: D000367:Age Factors; D000818:Animals; D001921:Brain / Q000166:cytology / Q000254:growth & development / Q000378:metabolism*; D015816:Cell Adhesion Molecules, Neuronal / Q000378:metabolism; D016326:Extracellular Matrix Proteins / Q000378:metabolism; D007150:Immunohistochemistry; D064326:MEF2 Transcription Factors; D008928:Mitochondria / Q000502:physiology; D018006:Myogenic Regulatory Factors / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000378:metabolism; D009473:Neuronal Plasticity / Q000502:physiology; D009474:Neurons / Q000378:metabolism*; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; D012333:RNA, Messenger / Q000032:analysis; D016601:RNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D051381:Rats; D000091042:Reelin Protein; D012697:Serine Endopeptidases / Q000378:metabolism; D013569:Synapses / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D005680:gamma-Aminobutyric Acid / Q000378:metabolism*
chemical_list: D015816:Cell Adhesion Molecules, Neuronal; D016326:Extracellular Matrix Proteins; D064326:MEF2 Transcription Factors; D018006:Myogenic Regulatory Factors; D009419:Nerve Tissue Proteins; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; C501429:Ppargc1a protein, rat; D012333:RNA, Messenger; D016601:RNA-Binding Proteins; D000091042:Reelin Protein; C000717129:Reln protein, rat; D014157:Transcription Factors; D005680:gamma-Aminobutyric Acid; C000717128:Reln protein, mouse; D012697:Serine Endopeptidases