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, Mark P. Mattson

Research output: Contribution to journalArticlepeer-review

325 Scopus citations

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.

Original languageEnglish
Article number1250
JournalNature Communications
Volume3
DOIs
StatePublished - 2012
Externally publishedYes

Bibliographical note

Funding Information:
This work was supported by the Intramural Research Programs of the National Institute on Aging. We thank Dr Heping Cheng (Peking University, China) for his critical reading and inputs. We thank Dr Marc Montminy (Salk Institute for Biological Studies) for the Ad-GFP-Si-PGC-1a and Ad-GFP-Si-Con) plasmids and Dr Pere Puigserver (John Hopkins University) for Ad-GFP-PGC-1a adenovirus.

Funding

This work was supported by the Intramural Research Programs of the National Institute on Aging. We thank Dr Heping Cheng (Peking University, China) for his critical reading and inputs. We thank Dr Marc Montminy (Salk Institute for Biological Studies) for the Ad-GFP-Si-PGC-1a and Ad-GFP-Si-Con) plasmids and Dr Pere Puigserver (John Hopkins University) for Ad-GFP-PGC-1a adenovirus.

FundersFunder number
National Institute on AgingZIAAG000317
Japan Society for the Promotion of Science23500971

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