The endocannabinoid system drives neural progenitor proliferation.
The FASEB Journal. 2005-10-01; 19(12): 1704-1706
DOI: 10.1096/fj.05-3995fje
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1. FASEB J. 2005 Oct;19(12):1704-6. Epub 2005 Jul 21.
The endocannabinoid system drives neural progenitor proliferation.
Aguado T(1), Monory K, Palazuelos J, Stella N, Cravatt B, Lutz B, Marsicano G,
Kokaia Z, Guzmán M, Galve-Roperh I.
Author information:
(1)Department of Biochemistry and Molecular Biology I, School of Biology,
Complutense University, Madrid, Spain.
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 CB1 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 CB1 receptor and the
endocannabinoid-inactivating enzyme fatty acid amide hydrolase (FAAH). CB1
receptor activation promotes cell proliferation and neurosphere generation, an
action that is abrogated in CB1-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.
DOI: 10.1096/fj.05-3995fje
PMID: 16037095 [Indexed for MEDLINE]