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Chronic Treatment with a Promnesiant GABA-A ?5-Selective Inverse Agonist Increases Immediate Early Genes Expression during Memory Processing in Mice and Rectifies Their Expression Levels in a Down Syndrome Mouse Model.


ABSTRACT: Decrease of GABAergic transmission has been proposed to improve memory functions. Indeed, inverse agonists selective for ?5 GABA-A-benzodiazepine receptors (?5IA) have promnesiant activity. Interestingly, we have recently shown that ?5IA 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 ?5IA 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 ?5IA increased IEGs expression, particularly of c-Fos and Arc genes. In Ts65Dn mice, deficits of IEGs activation were completely rescued after treatment with ?5IA. In addition, normalization of Sod1 overexpression in Ts65Dn mice after ?5IA treatment was observed. IEG expression regulation after ?5IA treatment following behavioral stimulation could be a contributing factor for both the general promnesiant activity of ?5IA and its rescuing effect in Ts65Dn mice alongside signaling cascades that are critical for memory consolidation and cognition.

SUBMITTER: Braudeau J 

PROVIDER: S-EPMC3199058 | BioStudies | 2011-01-01

REPOSITORIES: biostudies

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