%0 Generic %A Grégoire, Catherine-Alexandra %A Tobin, Stephanie %A Goldenstein, Brianna L. %A Samarut, Éric %A Leclerc, Andréanne %A Aumont, Anne %A Drapeau, Pierre %A Fulton, Stephanie %A J. L. Fernandes, Karl %D 2018 %T Table_3.PDF %U https://frontiersin.figshare.com/articles/dataset/Table_3_PDF/6137873 %R 10.3389/fnmol.2018.00126.s003 %2 https://frontiersin.figshare.com/ndownloader/files/11072081 %K dentate gyrus %K exercise %K RNA-sequencing %K social environment %K hippocampal neurogenesis %K environmental enrichment %X

Environmental enrichment (EE) is a powerful stimulus of brain plasticity and is among the most accessible treatment options for brain disease. In rodents, EE is modeled using multi-factorial environments that include running, social interactions, and/or complex surroundings. Here, we show that running and running-independent EE differentially affect the hippocampal dentate gyrus (DG), a brain region critical for learning and memory. Outbred male CD1 mice housed individually with a voluntary running disk showed improved spatial memory in the radial arm maze compared to individually- or socially-housed mice with a locked disk. We therefore used RNA sequencing to perform an unbiased interrogation of DG gene expression in mice exposed to either a voluntary running disk (RUN), a locked disk (LD), or a locked disk plus social enrichment and tunnels [i.e., a running-independent complex environment (CE)]. RNA sequencing revealed that RUN and CE mice showed distinct, non-overlapping patterns of transcriptomic changes versus the LD control. Bio-informatics uncovered that the RUN and CE environments modulate separate transcriptional networks, biological processes, cellular compartments and molecular pathways, with RUN preferentially regulating synaptic and growth-related pathways and CE altering extracellular matrix-related functions. Within the RUN group, high-distance runners also showed selective stress pathway alterations that correlated with a drastic decline in overall transcriptional changes, suggesting that excess running causes a stress-induced suppression of running’s genetic effects. Our findings reveal stimulus-dependent transcriptional signatures of EE on the DG, and provide a resource for generating unbiased, data-driven hypotheses for novel mediators of EE-induced cognitive changes.

%I Frontiers