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Neural Plasticity
Volume 2016, Article ID 3707406, 11 pages
Research Article

The Vitamin A Derivative All-Trans Retinoic Acid Repairs Amyloid-β-Induced Double-Strand Breaks in Neural Cells and in the Murine Neocortex

1Department of Psychiatry, University Hospital Geneva, Chêne-Bourg, 1225 Geneva, Switzerland
2Center for Psychiatric Neuroscience, Department of Psychiatry, CHUV, 1008 Lausanne-Prilly, Switzerland
3Department of Internal Medicine, Rehabilitation and Geriatrics, University Hospital of Geneva and University of Geneva, Thônex, 1226 Geneva, Switzerland
4Geneva Neuroscience Center, Geneva University, 1211 Geneva, Switzerland

Received 21 August 2015; Accepted 13 October 2015

Academic Editor: Daniela Merlo

Copyright © 2016 Emmanuelle Gruz-Gibelli et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.


The amyloid-β peptide or Aβ is the key player in the amyloid-cascade hypothesis of Alzheimer’s disease. Aβ appears to trigger cell death but also production of double-strand breaks (DSBs) in aging and Alzheimer’s disease. All-trans retinoic acid (RA), a derivative of vitamin A, was already known for its neuroprotective effects against the amyloid cascade. It diminishes, for instance, the production of Aβ peptides and their oligomerisation. In the present work we investigated the possible implication of RA receptor (RAR) in repair of Aβ-induced DSBs. We demonstrated that RA, as well as RAR agonist Am80, but not AGN 193109 antagonist, repair Aβ-induced DSBs in SH-SY5Y cells and an astrocytic cell line as well as in the murine cortical tissue of young and aged mice. The nonhomologous end joining pathway and the Ataxia Telangiectasia Mutated kinase were shown to be involved in RA-mediated DSBs repair in the SH-SY5Y cells. Our data suggest that RA, besides increasing cell viability in the cortex of young and even of aged mice, might also result in targeted DNA repair of genes important for cell or synaptic maintenance. This phenomenon would remain functional up to a point when Aβ increase and RA decrease probably lead to a pathological state.