| First Author | Cheng A | Year | 2012 |
| Journal | Nat Commun | Volume | 3 |
| Pages | 1250 | PubMed ID | 23212379 |
| Mgi Jnum | J:205615 | Mgi Id | MGI:5545936 |
| Doi | 10.1038/ncomms2238 | Citation | Cheng A, et al. (2012) Involvement of PGC-1alpha in the formation and maintenance of neuronal dendritic spines. Nat Commun 3:1250 |
| abstractText | 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 gamma co-activator 1alpha, a master regulator of mitochondrial biogenesis, in the formation and maintenance of dendritic spines in hippocampal neurons. In cultured hippocampal neurons, proliferator-activated receptor gamma co-activator 1alpha overexpression increases dendritic spines and enhances the molecular differentiation of synapses, whereas knockdown of proliferator-activated receptor gamma co-activator 1alpha inhibits spinogenesis and synaptogenesis. Proliferator-activated receptor gamma co-activator 1alpha 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 gamma co-activator-1alpha-dependent mitochondrial biogenesis by activating extracellular signal-regulated kinases and cyclic AMP response element-binding protein. Proliferator-activated receptor gamma co-activator-1alpha 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 gamma co-activator-1alpha and mitochondrial biogenesis have important roles in the formation and maintenance of hippocampal dendritic spines and synapses. |
