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Neuroscience ; 142(1): 125-37, 2006 Sep 29.
Artigo em Inglês | MEDLINE | ID: mdl-16859834

RESUMO

Adenosine is a potent modulator of excitatory neurotransmission, especially in seizure-prone regions such as the hippocampal formation. In adult brain ambient levels of adenosine are controlled by adenosine kinase (ADK), the major adenosine-metabolizing enzyme, expressed most strongly in astrocytes. Since ontogeny of the adenosine system is largely unknown, we investigated ADK expression and cellular localization during postnatal development of the mouse brain, using immunofluorescence staining with cell-type specific markers. At early postnatal stages ADK immunoreactivity was prominent in neurons, notably in cerebral cortex and hippocampus. Thereafter, as seen best in hippocampus, ADK gradually disappeared from neurons and appeared in newly developed nestin- and glial fibrillary acidic protein (GFAP)-positive astrocytes. Furthermore, the region-specific downregulation of neuronal ADK coincided with the onset of myelination, as visualized by myelin basic protein staining. After postnatal day 14 (P14), the transition from neuronal to astrocytic ADK expression was complete, except in a subset of neurons that retained ADK until adulthood in specific regions, such as striatum. Moreover, neuronal progenitors in the adult dentate gyrus lacked ADK. Finally, recordings of excitatory field potentials in acute slice preparations revealed a reduced adenosinergic inhibition in P14 hippocampus compared with adult. These findings suggest distinct roles for adenosine in the developing and adult brain. First, ADK expression in young neurons may provide a salvage pathway to utilize adenosine in nucleic acid synthesis, thus supporting differentiation and plasticity and influencing myelination; and second, adult ADK expression in astrocytes may offer a mechanism to regulate adenosine levels as a function of metabolic needs and synaptic activity, thus contributing to the differential resistance of young and adult animals to seizures.


Assuntos
Adenosina Quinase/metabolismo , Astrócitos/enzimologia , Encéfalo , Regulação da Expressão Gênica no Desenvolvimento/fisiologia , Neurônios/enzimologia , Fatores Etários , Animais , Animais Recém-Nascidos , Encéfalo/citologia , Encéfalo/enzimologia , Encéfalo/crescimento & desenvolvimento , Contagem de Células/métodos , Potenciais Pós-Sinápticos Excitadores/fisiologia , Potenciais Pós-Sinápticos Excitadores/efeitos da radiação , Proteína Glial Fibrilar Ácida/metabolismo , Imuno-Histoquímica/métodos , Técnicas In Vitro , Camundongos , Proteína Básica da Mielina/metabolismo , Neurônios/fisiologia , Técnicas de Patch-Clamp/métodos , Fosfopiruvato Hidratase/metabolismo
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