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Eur J Neurosci ; 24(6): 1535-45, 2006 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-17004917

RESUMO

Progress in the field of neurogenesis is limited by the lack of animal models allowing direct detection and analysis of living cells participating in neurogenesis. We engineered a transgenic mouse model that expresses the fluorescent reporter proteins enhanced green fluorescent protein or Discoma sp. reef coral red fluorescent protein under the control of the doublecortin (DCX) promoter, a gene specifically and transiently active in neuronal precursors and young neurons. The expression of the reporter proteins correlated with expression of the endogenous DCX protein, and with developmental and adult neurogenesis. Neurogenesis was unaffected by the presence of the fluorescent proteins. The transgenic mice allowed direct identification of the very few newly generated neurons present in the aged brain. We performed electrophysiological analysis and established that newly generated hippocampal granule cells in aged and young mice shared identical physiological properties. Hence, although the rate of neurogenesis tapers with ageing, a population of highly excitable young neurons indistinguishable to those found in younger animals is continuously generated. Therefore, maintenance of the fundamental properties of neuronal precursors even at advanced age suggests that stimulation of neurogenesis may constitute a valid strategy to counteract age-related neuronal loss and cognitive declines.


Assuntos
Expressão Gênica/fisiologia , Hipocampo/citologia , Proteínas Associadas aos Microtúbulos/metabolismo , Neurônios/fisiologia , Neuropeptídeos/metabolismo , Fatores Etários , Animais , Western Blotting/métodos , Bromodesoxiuridina/metabolismo , Carbocianinas/metabolismo , Proteínas do Domínio Duplacortina , Proteína Duplacortina , Proteína Glial Fibrilar Ácida/metabolismo , Proteínas de Fluorescência Verde/biossíntese , Imuno-Histoquímica/métodos , Técnicas In Vitro , Proteínas de Filamentos Intermediários/metabolismo , Proteínas Luminescentes/metabolismo , Potenciais da Membrana/fisiologia , Potenciais da Membrana/efeitos da radiação , Camundongos , Camundongos Transgênicos , Proteínas Associadas aos Microtúbulos/genética , Proteínas do Tecido Nervoso/metabolismo , Nestina , Neuropeptídeos/genética , Técnicas de Patch-Clamp/métodos , Regiões Promotoras Genéticas/fisiologia
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