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Here we elucidate a putative link between running, retinoid signaling, and neurogenesis in hippocampus. Adult transgenic reporter mice designed to detect ligand\u2010activated retinoic acid receptors (RAR) or retinoid X receptors (RXR) were used to localize the distribution of activated RAR or RXR at the single\u2010cell level in the brain. Two months of voluntary wheel\u2010running induced an increase in hippocampal neurogenesis as indicated by an almost two\u2010fold increase in doublecortin\u2010immunoreactive cells. Running activity was correlated with neurogenesis. Under basal conditions a distinct pattern of RAR\u2010activated cells was detected in the granule cell layer of the dentate gyrus (DG), thalamus, and cerebral cortex layers 3\u20134 and to a lesser extent in hippocampal pyramidal cell layers CA1\u2013CA3. Running did not change the number of RAR\u2010activated cells in the DG. There was no correlation between running and RAR activation or between RAR activation and neurogenesis in the DG of hippocampus. Only a few scattered activated retinoid X receptors were found in the DG under basal conditions and after wheel\u2010running, but RXR was detected in other areas such as in the hilus region of hippocampus and in layer VI of cortex cerebri. RAR agonists affect mood in humans and reduce neurogenesis, learning and memory in animal models. In our study, long\u2010term running increased neurogenesis but did not alter RAR ligand activation in the DG in individually housed mice. Thus, our data suggest that the effects of exercise on neurogenesis and other plasticity changes in the hippocampal formation are mediated by mechanisms that do not involve retinoid receptor activation. \u00a9 2008 Wiley\u2010Liss, Inc.<\/jats:p>","DOI":"10.1002\/hipo.20438","type":"journal-article","created":{"date-parts":[[2008,5,20]],"date-time":"2008-05-20T19:40:52Z","timestamp":1211312452000},"page":"785-792","source":"Crossref","is-referenced-by-count":18,"title":["Running increases neurogenesis without retinoic acid receptor activation in the adult mouse dentate 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