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

Susanne A Wolf12*, Anika Bick-Sander1, Klaus Fabel4, Perla Leal-Galicia4, Svantje Tauber2, Gerardo Ramirez-Rodriguez13, Anke Müller1, Andre Melnik2, Tim P Waltinger2, Oliver Ullrich2 and Gerd Kempermann14*

Author Affiliations

1 Max Delbrück Center for Molecular Medicine (MDC) Berlin-Buch, and Volkswagenstiftung Research Group, Department of Experimental Neurology, Charité University Medicine, Berlin, Germany

2 Institute of Anatomy, University of Zurich, Zurich, Switzerland

3 National Institute of Psychiatry "Ramón de la Fuente Muñiz", Neuropharmacology Department, Calz. México-Xochimilco 101, 14370 México, D.F. México

4 CRTD - Center for Regenerative Therapies Dresden, Dresden, Germany

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Cell Communication and Signaling 2010, 8:12  doi:10.1186/1478-811X-8-12

Published: 17 June 2010

Abstract

Background

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.

Results

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.

Conclusion

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.