Cannabinoids, the active components of marijuana and their endogenous counterparts, act on the brain and many other organs through the widely expressed CB 1 cannabinoid receptor. In contrast, the CB 2 cannabinoid receptor is abundant in the immune system and shows a restricted expression pattern in brain cells. CB 2 -selective agonists are, therefore, very attractive therapeutic agents as they do not cause CB 1 -mediated psychoactive effects. CB 2 receptor expression in brain has been partially examined in differentiated cells, while its presence and function in neural progenitor cells remain unknown. Here we show that the CB 2 receptor is expressed, both in vitro and in vivo , in neural progenitors from late embryonic stages to adult brain. Selective pharmacological activation of the CB 2 receptor in vitro promotes neural progenitor cell proliferation and neurosphere generation, an action that is impaired in CB 2 -deficient cells. Accordingly, in vivo experiments evidence that hippocampal progenitor proliferation is increased by administration of the CB 2 -selective agonist HU-308. Moreover, impaired progenitor proliferation was observed in CB 2 -deficient mice both in normal conditions and on kainate-induced excitotoxicity. These findings provide a novel physiological role for the CB 2 cannabinoid receptor and open a novel therapeutic avenue for manipulating neural progenitor cell fate.—Palazuelos, J., Aguado, T., Egia, A., Mechoulam, R., Guzmán, M., Galve-Roperh, I. Non-psychoactive CB 2 cannabinoid agonists stimulate neural progenitor proliferation.
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Non-psychoactive CB2 cannabinoid agonists stimulate neural progenitor proliferation
Palazuelos, Javier; Aguado, Tania; Egia, Ainara; Mechoulam, Raphael; Guzmán, Manuel; Galve-Roperh, Ismael
Follow The FASEB Journal
, Volume 20 (13): 2405
Fed of American Socs for Experimental Biology – Nov 1, 2006
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