GABA-cAMP response element-binding protein signaling regulates maturation and survival of newly generated neurons in the adult hippocampus.
J Neurosci
; 29(25): 7966-77, 2009 Jun 24.
Article
em En
| MEDLINE
| ID: mdl-19553437
ABSTRACT
Survival and integration of new neurons in the hippocampal circuit are rate-limiting steps in adult hippocampal neurogenesis. Neuronal network activity is a major regulator of these processes, yet little is known about the respective downstream signaling pathways. Here, we investigate the role of cAMP response element-binding protein (CREB) signaling in adult hippocampal neurogenesis. CREB is activated in new granule neurons during a distinct developmental period. Loss of CREB function in a cell-autonomous manner impairs dendritic development, decreases the expression of the neurogenic transcription factor NeuroD and of the neuronal microtubule-associated protein, doublecortin (DCX), and compromises the survival of newborn neurons. In addition, GABA-mediated excitation regulates CREB activation at early developmental stages. Importantly, developmental defects after loss of GABA-mediated excitation can be compensated by enhanced CREB signaling. These results indicate that CREB signaling is a central pathway in adult hippocampal neurogenesis, regulating the development and survival of new hippocampal neurons downstream of GABA-mediated excitation.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Neuropeptídeos
/
Transdução de Sinais
/
Proteína de Ligação ao Elemento de Resposta ao AMP Cíclico
/
Neurogênese
/
Ácido gama-Aminobutírico
/
Hipocampo
/
Camundongos
/
Proteínas Associadas aos Microtúbulos
/
Neurônios
Limite:
Animals
Idioma:
En
Revista:
J Neurosci
Ano de publicação:
2009
Tipo de documento:
Article