Reduced brain insulin-like growth factor I function during aging.
Mol Cell Neurosci
; 49(1): 9-12, 2012 Jan.
Article
em En
| MEDLINE
| ID: mdl-21807098
ABSTRACT
Peripheral insulin-like growth factor I (IGF-I) function progressively deteriorates with age. However, whereas deterioration of IGF-I function in the aged brain seems probable, it has not been directly addressed yet. Because serum IGF-I can enter into the brain through the cerebrospinal fluid (CSF), we examined this route of entrance in aged mice. To distinguish endogenous murine IGF-I from exogenously applied IGF-I, we used human IGF-I. We found that after intraperitoneous injection, CSF levels of human IGF-I were significantly higher in old mice (2 year-old) as compared to young ones (4-month-old). In spite of this increase capacity to take IGF-I from the circulation, brain and plasma IGF-I levels were reduced in naive old mice. Moreover, IGF-I signaling was deteriorated in the brain of aged animals. Basal as well as IGF-I-induced activation of the brain IGF-I receptor/Akt/GSK3 pathway was markedly reduced even though old mice have higher levels of brain IGF-I receptors. These data suggest that increases in brain IGF-I receptors and in the capacity to take up serum IGF-I result ineffective because IGF-I function is reduced and aged mice are cognitively impaired, a trait dependant on preserved serum IGF-I input to the brain.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Encéfalo
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Envelhecimento
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Fator de Crescimento Insulin-Like I
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Receptor IGF Tipo 1
Limite:
Animals
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Humans
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Male
Idioma:
En
Ano de publicação:
2012
Tipo de documento:
Article