Cannabinoid receptor CB1 mediates baseline and activity-induced survival of new neurons in adult hippocampal neurogenesis

<p>Abstract</p> <p>Background</p> <p>Adult neurogenesis is a particular example of brain plasticity that is partially modulated by the endocannabinoid system. Whereas the impact of synthetic cannabinoids on the neuronal progenitor cells has been described, there has been lack of information about the action of plant-derived extracts on neurogenesis. Therefore we here focused on the effects of Δ9-tetrahydrocannabinol (THC) and Cannabidiol (CBD) fed to female C57Bl/6 and Nestin-GFP-reporter mice on proliferation and maturation of neuronal progenitor cells and spatial learning performance. In addition we used cannabinoid receptor 1 (CB1) deficient mice and treatment with CB1 antagonist AM251 in Nestin-GFP-reporter mice to investigate the role of the CB1 receptor in adult neurogenesis in detail.</p> <p>Results</p> <p>THC and CBD differed in their effects on spatial learning and adult neurogenesis. CBD did not impair learning but increased adult neurogenesis, whereas THC reduced learning without affecting adult neurogenesis. We found the neurogenic effect of CBD to be dependent on the CB1 receptor, which is expressed over the whole dentate gyrus. Similarly, the neurogenic effect of environmental enrichment and voluntary wheel running depends on the presence of the CB1 receptor. We found that in the absence of CB1 receptors, cell proliferation was increased and neuronal differentiation reduced, which could be related to CB1 receptor mediated signaling in Doublecortin (DCX)-expressing intermediate progenitor cells.</p> <p>Conclusion</p> <p>CB1 affected the stages of adult neurogenesis that involve intermediate highly proliferative progenitor cells and the survival and maturation of new neurons. The pro-neurogenic effects of CBD might explain some of the positive therapeutic features of CBD-based compounds.</p

Running in pregnancy transiently increases postnatal hippocampal neurogenesis in the offspring

Voluntary wheel running of mice in pregnancy and lactation led to a twofold increase in hippocampal precursor-cell proliferation and in the number of Prox1-expressing lineage-determined cells at postnatal day 8 (P8). At P36, the number of newly generated granule cells approximately doubled, resulting in a 40% higher total number of granule cells in pups from running dams as compared with controls. Cell proliferation at embryonic day 15 (E15), in contrast, was decreased in the progeny of exercising mice, and the birth weight was reduced. At P49, body weight had normalized, and hippocampal neurogenesis was not different between the two groups. mRNA for FGF2 was expressed at higher levels at E15 and P8 in runner pups, whereas VEGF was increased only at E15. Insulin-like growth factor did not show differences at any time point. At P36, no differences for any of the factors were found. Our data indicate that maternal behavior and physical activity affects infantile growth-factor expression and can transiently stimulate postnatal hippocampal development in the offspring