Localization of the transcriptional coactivator PGC-1alpha to GABAergic neurons during maturation of the rat brain.
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.
Cowell
Rita Marie
RM
Department of Psychiatry, University of Alabama, Birmingham, Alabama 35294, USA.
Blake
Kathryn Rose
KR
Russell
James W
JW
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*
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