Neurotoxic and neuroprotective effects of glutamate are enhanced by introduction of amyloid precursor protein cDNA.
Brain Res
; 918(1-2): 121-30, 2001 Nov 09.
Article
em En
| MEDLINE
| ID: mdl-11684050
ABSTRACT
The physiological role of amyloid precursor protein (APP), whose anomalous metabolite is a putative pathogen for Alzheimer disease, remains unclear. From the enhanced responsiveness to glutamate in cultured hippocampal neurons after the introduction of cDNA of APP695 (an isoform of APP dominant in human brain) using an adenovirus vector, we have recently raised the hypothesis that APP modulates neuronal sensitivity to glutamate. To test this hypothesis, we utilized here the unique effects of glutamate on the survival of different types of neurons. It is known that hippocampal neurons undergo deterioration in 24 h after application of glutamate in a dose-dependent manner. This vulnerability was increased in the cells transfected with adenovirus carrying cDNA of APP695. By contrast, it is known that cerebellar granule neurons require for their survival the supplementation of NMDA to the medium. The dose of NMDA required for survival was reduced after the transfection of the APP-adenovirus to cerebellar granule neurons. These enhancing effects of APP on the glutamate-induced vulnerability in hippocampal neurons and the glutamate (NMDA)-dependent survival in cerebellar neurons were blocked by glutamate receptor inhibitors, and were not seen after application of a control adenovirus carrying cDNA of beta-galactosidase. Since the effects of glutamate were enhanced in both directions, the hypothesis became more likely that one of the physiological functions of cellular APP is the regulation of glutamate receptors.
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Coleções:
01-internacional
Temas:
Geral
Base de dados:
MEDLINE
Assunto principal:
Encéfalo
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Sobrevivência Celular
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Precursor de Proteína beta-Amiloide
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Receptores de Glutamato
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Ácido Glutâmico
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Neurônios
Limite:
Animals
Idioma:
En
Revista:
Brain Res
Ano de publicação:
2001
Tipo de documento:
Article
País de afiliação:
Japão