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Localization of the transcriptional coactivator PGC‐1α to GABAergic neurons during maturation of the rat brain
Author(s) -
Cowell Rita Marie,
Blake Kathryn Rose,
Russell James W.
Publication year - 2007
Publication title -
journal of comparative neurology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.855
H-Index - 209
eISSN - 1096-9861
pISSN - 0021-9967
DOI - 10.1002/cne.21211
Subject(s) - biology , gabaergic , coactivator , forebrain , striatum , cerebellum , mitochondrial biogenesis , reelin , hippocampus , cerebral cortex , endocrinology , medicine , microbiology and biotechnology , neuroscience , transcription factor , mitochondrion , central nervous system , dopamine , genetics , inhibitory postsynaptic potential , extracellular matrix , gene
The transcriptional coactivator peroxisome proliferator activated receptor γ coactivator 1α (PGC‐1α) 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‐1α knockout mice exhibit behavioral abnormalities and progressive vacuolization in various brain regions. To investigate the roles for PGC‐1α in the nervous system, we evaluated the temporal and cell‐specific expression of PGC‐1α in the normal developing rat brain. Western blot of whole brain homogenates with a PGC‐1α‐specific antibody revealed that PGC‐1α 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‐1α 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‐1α 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‐1α 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‐1α expression. These results implicate PGC‐1α 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‐1α may be a good target for increasing metabolism in GABAergic populations in neurodevelopmental and neurodegenerative disorders. J. Comp. Neurol. 502:1–18, 2007. © 2007 Wiley‐Liss, Inc.