On the in vivo early toxic properties of A-beta 25-35 peptide in the rat hippocampus: involvement of the Receptor-for-Advanced Glycation-End-Products and changes in gene expression.
Neurotoxicol Teratol
; 33(2): 288-96, 2011.
Article
em En
| MEDLINE
| ID: mdl-21216281
ABSTRACT
Amyloid-beta peptide (Aß) deposition is assumed to play a pathogenic role in the brain of Alzheimer's disease patients. To date, the precise mechanisms underlying Aß toxicity are not fully understood. A recent hypothesis suggesting that the Receptor-for-Advanced-Glycation-End-Products (RAGE)-a trans-membrane protein signaling for oxidative stress-is involved in Aß toxicity is gaining attention. Early Aß toxicity could indeed help to explain the deleterious events further produced by this molecule in the brain. In this work, we evaluated the pattern of early expression of RAGE in the toxic model induced by Aß25â35 in rat CA1 region. Intrahippocampal injections of Aß25â35 in rats increased the RAGE expression at 24 h post-injection; this event was accompanied by increased components of RAGE downstream signaling in hippocampal cells, such as enhanced expression of the pro-apoptotic factor NF-κB, increased nitric oxide production, LDH leakage, mitochondrial dysfunction, increased TNF-α expression, antioxidant genes down-regulation, and augmented neurodegeneration. Our findings support an active role of RAGE during the early stages of Aß25â35 toxicity in the hippocampus.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Fragmentos de Peptídeos
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Receptores Imunológicos
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Expressão Gênica
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Peptídeos beta-Amiloides
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Região CA1 Hipocampal
Tipo de estudo:
Prognostic_studies
Limite:
Animals
Idioma:
En
Ano de publicação:
2011
Tipo de documento:
Article