On the in vivo early toxic properties of Aβ25-35 peptide in the rat hippocampus: Involvement of the Receptor-for-Advanced Glycation-End-Products and changes in gene expression

Elvis Cuevas, Susan M. Lantz, J. César Tobón-Velasco, Glenn D. Newport, Qiangen Wu, Ashraf Virmani, Syed F. Ali, Abel Santamaría

Research output: Contribution to journalArticlepeer-review

21 Scopus citations

Abstract

Amyloid-beta peptide (Aβ) deposition is assumed to play a pathogenic role in the brain of Alzheimer's disease patients. To date, the precise mechanisms underlying Aβ 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 Aβ toxicity is gaining attention. Early Aβ 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 Aß25-35 in rat CA1 region. Intrahippocampal injections of Aβ25-35 in rats increased the RAGE expression at 24h 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-αB, increased nitric oxide production, LDH leakage, mitochondrial dysfunction, increased TNF-κ expression, antioxidant genes down-regulation, and augmented neurodegeneration. Our findings support an active role of RAGE during the early stages of Aα25-35 toxicity in the hippocampus.

Original languageEnglish (US)
Pages (from-to)288-296
Number of pages9
JournalNeurotoxicology and Teratology
Volume33
Issue number2
DOIs
StatePublished - Mar 2011
Externally publishedYes

Keywords

  • Amyloid-α
  • Gene expression
  • Neurodegeneration
  • Neurotoxicity
  • Oxidative stress
  • Receptor-for-Advanced Glycation-End-Products

ASJC Scopus subject areas

  • Toxicology
  • Developmental Neuroscience
  • Cellular and Molecular Neuroscience

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