RGD Reference Report - AMP-activated protein kinase mediates activity-dependent regulation of peroxisome proliferator-activated receptor gamma coactivator-1alpha and nuclear respiratory factor 1 expression in rat visual cortical neurons. - Rat Genome Database
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AMP-activated protein kinase mediates activity-dependent regulation of peroxisome proliferator-activated receptor gamma coactivator-1alpha and nuclear respiratory factor 1 expression in rat visual cortical neurons.

Authors: Yu, L  Yang, SJ 
Citation: Yu L and Yang SJ, Neuroscience. 2010 Aug 11;169(1):23-38. doi: 10.1016/j.neuroscience.2010.04.063. Epub 2010 May 18.
RGD ID: 10059668
Pubmed: (View Article at PubMed) PMID:20438809
DOI: Full-text: DOI:10.1016/j.neuroscience.2010.04.063

Nuclear respiratory factor 1 (NRF-1) is one of the key transcription factors implicated in mitochondrial biogenesis by activating the transcription of mitochondrial transcription factor A (mtTFA) and subunit genes of respiratory enzymes. NRF-1 transactivation activity can be enhanced by interaction with transcription coactivator peroxisome proliferator-activated receptor gamma coactivator 1alpha (PGC-1alpha). The expression of PGC-1alpha, NRF-1 and mtTFA in neurons is known to be tightly regulated by neuronal activity. However, the coupling signaling mechanism is poorly understood. Here, we use primary cultures of rat visual cortical neurons and a rat model of monocular deprivation (MD) to investigate whether AMP-activated protein kinase (AMPK) is implicated in mediating activity-dependent regulation of PGC-1alpha and NRF-1 expression in neurons. We find that KCl depolarization rapidly activates AMPK and significantly increases PGC-1alpha, NRF-1, and mtTFA levels with increased ATP production in neuron cultures. Similarly, pharmacological activation of AMPK with 5'-aminoimidazole-4-carboxamide riboside (AICAR) or resveratrol also markedly increases PGC-1alpha and NRF-1 mRNA levels in neuron cultures. All these effects can be completely blocked by an AMPK inhibitor, Compound C. Conversely, 1 week of MD significantly reduces AMPK phosphorylation and activity, dramatically down-regulates PGC-1alpha and NRF-1 expression in deprived primary visual cortex. Administration of resveratrol in vivo significantly activates AMPK activity and attenuates the effects of MD on mitochondria by significant increase in PGC-1alpha and NRF-1 levels, mitochondria amount, and coupled respiration. These results strongly indicate that AMPK is an essential upstream mediator that couples neuronal activity to mitochondrial energy metabolism by regulation of PGC-1alpha-NRF-1 pathway in neurons.

Annotation

Disease Annotations    
amblyopia  (IEP,ISO)

Gene Ontology Annotations    

Biological Process

Objects Annotated

Genes (Rattus norvegicus)
Ppargc1a  (PPARG coactivator 1 alpha)

Genes (Mus musculus)
Ppargc1a  (peroxisome proliferative activated receptor, gamma, coactivator 1 alpha)

Genes (Homo sapiens)
PPARGC1A  (PPARG coactivator 1 alpha)


Additional Information