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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
21
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pubmed:dateCreated |
2010-5-27
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pubmed:abstractText |
The transcriptional coactivator peroxisome proliferator-activated receptor gamma coactivator 1alpha (PGC-1alpha) is a master regulator of metabolism in peripheral tissues, and it has been proposed that PGC-1alpha plays a similar role in the brain. Recent evidence suggests that PGC-1alpha is concentrated in GABAergic interneurons, so we investigated whether male and female PGC-1alpha -/- mice exhibit abnormalities in interneuron gene expression and/or function. We found a striking reduction in the expression of the Ca(2+)-binding protein parvalbumin (PV), but not other GABAergic markers, throughout the cerebrum in PGC-1alpha +/- and -/- mice. Furthermore, PGC-1alpha overexpression in cell culture was sufficient to robustly induce PV expression. Consistent with a reduction in PV rather than a loss of PV-expressing interneurons, spontaneous synaptic inhibition was not altered in PGC-1alpha -/- mice. However, evoked synaptic responses displayed less paired-pulse depression and dramatic facilitation in response to repetitive stimulation at the gamma frequency. PV transcript expression was also significantly reduced in retina and heart of PGC-1alpha -/- animals, suggesting that PGC-1alpha is required for proper expression of PV in multiple tissues. Together these findings indicate that PGC-1alpha is a novel regulator of interneuron gene expression and function and a potential therapeutic target for neurological disorders associated with interneuron dysfunction.
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pubmed:grant |
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/DNA-Binding Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/GLUT4 enhancer factor, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/GTP Phosphohydrolases,
http://linkedlifedata.com/resource/pubmed/chemical/Glutamate Decarboxylase,
http://linkedlifedata.com/resource/pubmed/chemical/High Mobility Group Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Mfn2 protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/Parvalbumins,
http://linkedlifedata.com/resource/pubmed/chemical/Ppargc1a protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/RNA, Messenger,
http://linkedlifedata.com/resource/pubmed/chemical/Shaw Potassium Channels,
http://linkedlifedata.com/resource/pubmed/chemical/Tfam protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/Trans-Activators,
http://linkedlifedata.com/resource/pubmed/chemical/Transcription Factors,
http://linkedlifedata.com/resource/pubmed/chemical/gamma-Aminobutyric Acid,
http://linkedlifedata.com/resource/pubmed/chemical/glutamate decarboxylase 1,
http://linkedlifedata.com/resource/pubmed/chemical/glutamate decarboxylase 2
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pubmed:status |
MEDLINE
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pubmed:month |
May
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pubmed:issn |
1529-2401
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pubmed:author |
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pubmed:issnType |
Electronic
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pubmed:day |
26
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pubmed:volume |
30
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
7227-35
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pubmed:dateRevised |
2011-9-26
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pubmed:meshHeading |
pubmed-meshheading:20505089-Analysis of Variance,
pubmed-meshheading:20505089-Animals,
pubmed-meshheading:20505089-Animals, Newborn,
pubmed-meshheading:20505089-Biophysics,
pubmed-meshheading:20505089-Cells, Cultured,
pubmed-meshheading:20505089-DNA-Binding Proteins,
pubmed-meshheading:20505089-Electric Stimulation,
pubmed-meshheading:20505089-GTP Phosphohydrolases,
pubmed-meshheading:20505089-Gene Expression Regulation, Developmental,
pubmed-meshheading:20505089-Glutamate Decarboxylase,
pubmed-meshheading:20505089-Heart,
pubmed-meshheading:20505089-High Mobility Group Proteins,
pubmed-meshheading:20505089-Hippocampus,
pubmed-meshheading:20505089-Humans,
pubmed-meshheading:20505089-Inhibitory Postsynaptic Potentials,
pubmed-meshheading:20505089-Interneurons,
pubmed-meshheading:20505089-Long-Term Potentiation,
pubmed-meshheading:20505089-Mice,
pubmed-meshheading:20505089-Mice, Inbred C57BL,
pubmed-meshheading:20505089-Mice, Knockout,
pubmed-meshheading:20505089-Myocardium,
pubmed-meshheading:20505089-Parvalbumins,
pubmed-meshheading:20505089-Patch-Clamp Techniques,
pubmed-meshheading:20505089-RNA, Messenger,
pubmed-meshheading:20505089-Shaw Potassium Channels,
pubmed-meshheading:20505089-Trans-Activators,
pubmed-meshheading:20505089-Transcription Factors,
pubmed-meshheading:20505089-Transfection,
pubmed-meshheading:20505089-gamma-Aminobutyric Acid
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pubmed:year |
2010
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pubmed:articleTitle |
Parvalbumin deficiency and GABAergic dysfunction in mice lacking PGC-1alpha.
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pubmed:affiliation |
Department of Psychology, University of Alabama at Birmingham, Birmingham, Alabama 35294, USA.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't,
Research Support, N.I.H., Extramural
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