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The endocannabinoid system drives neural progenitor proliferation
Author(s) -
Aguado Tania,
Monory Krisztina,
Palazuelos Javier,
Stella‡ Nephi,
Cravatt Benjamin,
Lutz Beat,
Marsicano Giovanni,
Kokaia Zaal,
Guzmán Manuel,
GalveRoperh Ismael
Publication year - 2005
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fj.05-3995fje
Subject(s) - endocannabinoid system , neurogenesis , cannabinoid receptor , fatty acid amide hydrolase , neural stem cell , progenitor cell , anandamide , microbiology and biotechnology , cannabinoid , biology , cell growth , neuroscience , receptor , chemistry , stem cell , biochemistry , agonist
The discovery of multipotent neural progenitor (NP) cells has provided strong support for the existence of neurogenesis in the adult brain. However, the signals controlling NP proliferation remain elusive. Endocannabinoids, the endogenous counterparts of marijuana‐derived cannabinoids, act as neuromodulators via presynaptic CB 1 receptors and also control neural cell death and survival. Here we show that progenitor cells express a functional endocannabinoid system that actively regulates cell proliferation both in vitro and in vivo. Specifically, NPs produce endocannabinoids and express the CB 1 receptor and the endocannabinoid‐inactivating enzyme fatty acid amide hydrolase (FAAH). CB 1 receptor activation promotes cell proliferation and neurosphere generation, an action that is abrogated in CB 1 ‐deficient NPs. Accordingly, proliferation of hippocampal NPs is increased in FAAH‐deficient mice. Our results demonstrate that endocannabinoids constitute a new group of signaling cues that regulate NP proliferation and thus open novel therapeutic avenues for manipulation of NP cell fate in the adult brain.