On the in vivo early toxic properties of Aβ 25–35 peptide in the rat hippocampus: Involvement of the Receptor-for-Advanced Glycation-End-Products and changes in gene expression

• Published in: Neurotoxicology and teratology Vol. 33; no. 2; pp. 288 - 296
• Main Authors: Cuevas, Elvis, Lantz, Susan M., Tobón-Velasco, J. César, Newport, Glenn D., Wu, Qiangen, Virmani, Ashraf, Ali, Syed F., Santamaría, Abel
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.03.2011
• Subjects: Amyloid beta-Peptides - toxicity; Amyloid-β 25–35; Animals; Antioxidants - metabolism; Blotting, Western; CA1 Region, Hippocampal - drug effects; CA1 Region, Hippocampal - enzymology; CA1 Region, Hippocampal - metabolism; CA1 Region, Hippocampal - pathology; Cell Death - drug effects; Gene expression; Gene Expression - drug effects; Male; Microinjections; Microscopy, Fluorescence; Mitochondria - drug effects; Mitochondria - physiology; Neurodegeneration; Neurotoxicity; Nitric Oxide - biosynthesis; Oxidative stress; Oxidative Stress - drug effects; Oxidative Stress - genetics; Peptide Fragments - toxicity; Rats; Rats, Sprague-Dawley; Receptor for Advanced Glycation End Products; Receptors, Immunologic - genetics; Reverse Transcriptase Polymerase Chain Reaction; Oxidative stress; Amyloid-β 25–35; Neurotoxicity; Receptor-for-Advanced Glycation-End-Products; Gene expression; Neurodegeneration
• ISSN: 0892-0362; 1872-9738
• DOI: 10.1016/j.ntt.2010.12.002

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 Aß 25–35 in rat CA1 region. Intrahippocampal injections of Aβ 25–35 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 Aβ 25–35 toxicity in the hippocampus.