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Advances in Pharmacological Sciences
Volume 2011, Article ID 153218, 11 pages
http://dx.doi.org/10.1155/2011/153218
Research Article

Chronic Treatment with a Promnesiant GABA-A 𝜢 πŸ“ -Selective Inverse Agonist Increases Immediate Early Genes Expression during Memory Processing in Mice and Rectifies Their Expression Levels in a Down Syndrome Mouse Model

1Centre de Recherche de l'Institut du Cerveau et de Moelle Epinière, INSERM UMRS 975, CNRS UMR7225, UPMC, 75013 Paris, France
2Institut de Génétique et de Biologie Moléculaire et Cellulaire (IGBMC), Institut National de Santé et de Recherche Médicale (INSERM) U964/Centre National de Recherche Scientifique (CNRS) UMR 1704/Université de Strasbourg, 67404 Illkirch, France
3Institut de Chimie des Substances Naturelles-CNRS UPR 2301, 91198 Gif-sur-Yvette, France
4Groupe d'Intérêt Economique-Centre Européen de Recherche en Biologie et en Médecine (GIE-CERBM), Institut Clinique de la Souris (ICS), Université de Strasbourg, 67404 Illkirch, France

Received 6 April 2011; Revised 27 July 2011; Accepted 31 July 2011

Academic Editor: Naheed R. Mirza

Copyright © 2011 J. Braudeau 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.

Abstract

Decrease of GABAergic transmission has been proposed to improve memory functions. Indeed, inverse agonists selective for α5 GABA-A-benzodiazepine receptors (α5IA) have promnesiant activity. Interestingly, we have recently shown that α5IA can rescue cognitive deficits in Ts65Dn mice, a Down syndrome mouse model with altered GABAergic transmission. Here, we studied the impact of chronic treatment with α5IA on gene expression in the hippocampus of Ts65Dn and control euploid mice after being trained in the Morris water maze task. In euploid mice, chronic treatment with α5IA increased IEGs expression, particularly of c-Fos and Arc genes. In Ts65Dn mice, deficits of IEGs activation were completely rescued after treatment with α5IA. In addition, normalization of Sod1 overexpression in Ts65Dn mice after α5IA treatment was observed. IEG expression regulation after α5IA treatment following behavioral stimulation could be a contributing factor for both the general promnesiant activity of α5IA and its rescuing effect in Ts65Dn mice alongside signaling cascades that are critical for memory consolidation and cognition.