Artículo
Activity-dependent BDNF release and TRPC signaling is impaired in hippocampal neurons of Mecp2 mutant mice
Fecha de publicación:
16/10/2012
Editorial:
National Academy of Sciences
Revista:
Proceedings of the National Academy of Sciences of The United States of America
ISSN:
0027-8424
Idioma:
Inglés
Tipo de recurso:
Artículo publicado
Clasificación temática:
Resumen
Dysfunction of the neurotrophin brain-derived neurotrophic factor (BDNF) is implicated in Rett syndrome (RTT), but the state of its releasable pool and downstream signaling in mice lacking methyl-CpG-binding protein-2 (Mecp2) is unknown. Here, we show that membrane currents and dendritic Ca2+ signals evoked by recombinant BDNF or an activator of diacylglycerol (DAG)-sensitive transient receptor potential canonical (TRPC) channels are impaired in CA3 pyramidal neurons of symptomatic Mecp2 mutant mice. TRPC3 and TRPC6 mRNA and protein levels are lower in Mecp2 mutant hippocampus, and chromatin immunoprecipitation (ChIP) identified Trpc3 as a target of MeCP2 transcriptional regulation. BDNF mRNA and protein levels are also lower in Mecp2 mutant hippocampus and dentate gyrus granule cells, which is reflected in impaired activity-dependent release of endogenous BDNF estimated from TRPC currents and dendritic Ca2+ signals in CA3 pyramidal neurons. These results identify the gene encoding TRPC3 channels as a MeCP2 target and suggest a potential therapeutic strategy to boost impaired BDNF signaling in RTT.
Palabras clave:
MECP2
,
RETT SYNDROME
,
TRPC3
,
HIPPOCAMPUS
Archivos asociados
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Identificadores
Colecciones
Articulos(IFEC)
Articulos de INST. DE FARMACOLOGIA EXPERIMENTAL DE CORDOBA
Articulos de INST. DE FARMACOLOGIA EXPERIMENTAL DE CORDOBA
Citación
Li, Wei; Calfa, Gaston Diego; Larimore, Jennifer; Pozzo-Miller, Lucas; Activity-dependent BDNF release and TRPC signaling is impaired in hippocampal neurons of Mecp2 mutant mice; National Academy of Sciences; Proceedings of the National Academy of Sciences of The United States of America; 109; 42; 16-10-2012; 17087-17092
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