Involvement of PGC-1α in the formation and maintenance of neuronal dendritic spines

Aiwu Cheng (), Ruiqian Wan, Jenq-Lin Yang, Naomi Kamimura, Tae Gen Son, Xin Ouyang, Yongquan Luo, Eitan Okun and Mark P. Mattson
Additional contact information
Aiwu Cheng: Laboratory of Neurosciences, National Institute on Aging Intramural Research Program
Ruiqian Wan: Laboratory of Neurosciences, National Institute on Aging Intramural Research Program
Jenq-Lin Yang: Laboratory of Neurosciences, National Institute on Aging Intramural Research Program
Naomi Kamimura: Laboratory of Neurosciences, National Institute on Aging Intramural Research Program
Tae Gen Son: Laboratory of Neurosciences, National Institute on Aging Intramural Research Program
Xin Ouyang: Laboratory of Neurosciences, National Institute on Aging Intramural Research Program
Yongquan Luo: Laboratory of Neurosciences, National Institute on Aging Intramural Research Program
Eitan Okun: Laboratory of Neurosciences, National Institute on Aging Intramural Research Program
Mark P. Mattson: Laboratory of Neurosciences, National Institute on Aging Intramural Research Program

Nature Communications, 2012, vol. 3, issue 1, 1-12

Abstract: Abstract The formation, maintenance and reorganization of synapses are critical for brain development and the responses of neuronal circuits to environmental challenges. Here we describe a novel role for peroxisome proliferator-activated receptor γ co-activator 1α, a master regulator of mitochondrial biogenesis, in the formation and maintenance of dendritic spines in hippocampal neurons. In cultured hippocampal neurons, proliferator-activated receptor γ co-activator 1α overexpression increases dendritic spines and enhances the molecular differentiation of synapses, whereas knockdown of proliferator-activated receptor γ co-activator 1α inhibits spinogenesis and synaptogenesis. Proliferator-activated receptor γ co-activator 1α knockdown also reduces the density of dendritic spines in hippocampal dentate granule neurons in vivo. We further show that brain-derived neurotrophic factor stimulates proliferator-activated receptor γ co-activator-1α-dependent mitochondrial biogenesis by activating extracellular signal-regulated kinases and cyclic AMP response element-binding protein. Proliferator-activated receptor γ co-activator-1α knockdown inhibits brain-derived neurotrophic factor-induced dendritic spine formation without affecting expression and activation of the brain-derived neurotrophic factor receptor tyrosine receptor kinase B. Our findings suggest that proliferator-activated receptor γ co-activator-1α and mitochondrial biogenesis have important roles in the formation and maintenance of hippocampal dendritic spines and synapses.

Date: 2012
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DOI: 10.1038/ncomms2238

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