G-Protein-Associated Signal Transduction Processes Are Restored after Postweaning Environmental Enrichment in Ts65Dn, a Down Syndrome Mouse Model

Abstract

Individuals with Down syndrome (DS) present cognitive deficits that can be improved by early implementation of special care programs. However, they showed limited and temporary cognitive effects. We previously demonstrated that postnatal environmental enrichment (EE) improved clearly, though temporarily, the execution of visuospatial memory tasks in Ts65Dn mice, a DS model bearing a partial trisomy of murine chromosome 16; but in contrast to wild-type littermates, there was a lack of structural plasticity in pyramidal cell structure in the trisomic cerebral cortex. In the present study, we have investigated the impact of EE on the function of adenylyl cyclase and phospholipase C as a possible mechanism underlying the time-limited improvements observed. Basal production of cyclic adenosine monophosphate (cAMP) was not affected, but responses to GTPγS, isoprenaline, noradrenaline, SKF 38393 and forskolin were depressed in the Ts65Dn hippocampus. In EE conditions, cAMP accumulation was not significantly modified in control animals with respect to nonenriched controls. However, EE had a marked effect in Ts65Dn mice, in which cAMP production was significantly increased. Similarly, EE increased phospholipase C activity in Ts65Dn mice, in response to carbachol and calcium. We conclude that EE restores the G-protein-associated signal transduction systems that are altered in Ts65Dn mice.