2014 journal article
PGC-1 Provides a Transcriptional Framework for Synchronous Neurotransmitter Release from Parvalbumin-Positive Interneurons
Journal of Neuroscience, 34(43), 14375–14387.
author keywords: Barnes maze; cortical development; Huntington disease; ppargc1a; schizophrenia; strontium
MeSH headings : Animals; Cell Line, Tumor; Humans; Interneurons / metabolism; Male; Mice; Mice, Inbred C57BL; Mice, Knockout; Mice, Transgenic; Parvalbumins / biosynthesis; Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; Transcription Factors / biosynthesis; Transcription, Genetic / physiology; gamma-Aminobutyric Acid / metabolism
TL;DR:
Conditional deletion of PGC-1α in PV-positive neurons significantly decreased cortical transcript expression of these genes, promoted asynchronous GABA release, and impaired long-term memory, demonstrating that loss of P GC-1 α in this interneuron subpopulation could contribute to cortical dysfunction in disease states.
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www.jneurosci.org (publisher PDF)
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Added: July 27, 2019
Accumulating evidence strongly implicates the transcriptional coactivator peroxisome proliferator-activated receptor γ coactivator 1α (PGC-1α) in the pathophysiology of multiple neurological disorders, but the downstream gene targets of PGC-1α in the brain have remained enigmatic. Previous data demonstrate that PGC-1α is primarily concentrated in inhibitory neurons and that PGC-1α is required for the expression of the interneuron-specific Ca2+-binding protein parvalbumin (PV) throughout the cortex. To identify other possible transcriptional targets of PGC-1α in neural tissue, we conducted a microarray on neuroblastoma cells overexpressing PGC-1α, mined results for genes with physiological relevance to interneurons, and measured cortical gene and protein expression of these genes in mice with underexpression and overexpression of PGC-1α. We observed bidirectional regulation of novel PGC-1α-dependent transcripts spanning synaptic [synaptotagmin 2 (Syt2) and complexin 1 (Cplx1)], structural [neurofilament heavy chain (Nefh)], and metabolic [neutral cholesterol ester hydrolase 1 (Nceh1), adenylate kinase 1 (Ak1), inositol polyphosphate 5-phosphatase J (Inpp5j), ATP synthase mitochondrial F1 complex O subunit (Atp5o), phytanol-CoA-2hydroxylase (Phyh), and ATP synthase mitrochondrial F1 complex α subunit 1 (Atp5a1)] functions. The neuron-specific genes Syt2, Cplx1, and Nefh were developmentally upregulated in an expression pattern consistent with that of PGC-1α and were expressed in cortical interneurons. Conditional deletion of PGC-1α in PV-positive neurons significantly decreased cortical transcript expression of these genes, promoted asynchronous GABA release, and impaired long-term memory. Collectively, these data demonstrate that PGC-1α is required for normal PV-positive interneuron function and that loss of PGC-1α in this interneuron subpopulation could contribute to cortical dysfunction in disease states.
