title: Involvement of PGC-1α in the formation and maintenance of neuronal dendritic spines.
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.
authors.affiliation: Laboratory of Neurosciences, National Institute on Aging Intramural Research Program, Baltimore, Maryland 21224, USA. chengai@mail.nih.gov
authors.forename: Aiwu
authors.initials: A
authors.lastname: Cheng
authors.forename: Ruiqian
authors.initials: R
authors.lastname: Wan
authors.forename: Jenq-Lin
authors.initials: JL
authors.lastname: Yang
authors.forename: Naomi
authors.initials: N
authors.lastname: Kamimura
authors.forename: Tae Gen
authors.initials: TG
authors.lastname: Son
authors.forename: Xin
authors.initials: X
authors.lastname: Ouyang
authors.forename: Yongquan
authors.initials: Y
authors.lastname: Luo
authors.forename: Eitan
authors.initials: E
authors.lastname: Okun
authors.forename: Mark P
authors.initials: MP
authors.lastname: Mattson
mesh_terms: D000818:Animals; D019208:Brain-Derived Neurotrophic Factor / Q000502:physiology; D017362:Cyclic AMP Response Element-Binding Protein / Q000502:physiology; D049229:Dendritic Spines / Q000502:physiology*; D018891:Dentate Gyrus / Q000166:cytology / Q000502:physiology; D006624:Hippocampus / Q000166:cytology / Q000196:embryology; D051379:Mice; D008928:Mitochondria / Q000378:metabolism / Q000502:physiology; D020929:Mitogen-Activated Protein Kinase Kinases / Q000502:physiology; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; D016133:Polymerase Chain Reaction; D016601:RNA-Binding Proteins / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013569:Synapses / Q000502:physiology; D014157:Transcription Factors / Q000502:physiology*; D015854:Up-Regulation / Q000502:physiology
chemical_list: D019208:Brain-Derived Neurotrophic Factor; D017362:Cyclic AMP Response Element-Binding Protein; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; C501429:Ppargc1a protein, rat; D016601:RNA-Binding Proteins; D014157:Transcription Factors; D020929:Mitogen-Activated Protein Kinase Kinases