The CB1 cannabinoid receptor mediates excitotoxicity-induced neural progenitor proliferation and neurogenesis.

Tania Aguado, Eva Romero, Krisztina Monory, Javier Palazuelos, Michael Sendtner, Giovanni Marsicano, Beat Lutz, Manuel Guzmán, Ismael Galve-Roperh
J. Biol. Chem.. 2007-06-07; 282(33): 23892-23898
DOI: 10.1074/jbc.m700678200

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1. J Biol Chem. 2007 Aug 17;282(33):23892-8. Epub 2007 Jun 7.

The CB1 cannabinoid receptor mediates excitotoxicity-induced neural progenitor
proliferation and neurogenesis.

Aguado T(1), Romero E, Monory K, Palazuelos J, Sendtner M, Marsicano G, Lutz B,
Guzmán M, Galve-Roperh I.

Author information:
(1)Department of Biochemistry and Molecular Biology I, School of Biology, and
Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas
(CIBERNED), Complutense University, 28040 Madrid, Spain.

Erratum in
J Biol Chem. 2008 Feb 29;283(9):5971.

Endocannabinoids are lipid signaling mediators that exert an important
neuromodulatory role and confer neuroprotection in several types of brain injury.
Excitotoxicity and stroke can induce neural progenitor (NP) proliferation and
differentiation as an attempt of neuroregeneration after damage. Here we
investigated the mechanism of hippocampal progenitor cell engagement upon
excitotoxicity induced by kainic acid administration and the putative involvement
of the CB1 cannabinoid receptor in this process. Adult NPs express kainate
receptors that mediate proliferation and neurosphere generation in vitro via CB1
cannabinoid receptors. Similarly, in vivo studies showed that
excitotoxicity-induced hippocampal NPs proliferation and neurogenesis are
abrogated in CB1-deficient mice and in wild-type mice administered with the
selective CB1 antagonist rimonabant
amide; SR141716). Kainate stimulation increased basic fibroblast growth factor
(bFGF) expression in cultured NPs in a CB1-dependent manner as this response was
prevented by rimonabant and mimicked by endocannabinoids. Likewise, in vivo
analyses showed that increased hippocampal expression of bFGF, as well as of
brain-derived neurotrophic factor and epidermal growth factor, occurs upon
excitotoxicity and that CB1 receptor ablation prevents this induction. Moreover,
excitotoxicity increased the number of CB1+ bFGF+ cells, and this up-regulation
preceded NP proliferation. In summary, our results show the involvement of the
CB1 cannabinoid receptor in NP proliferation and neurogenesis induced by
excitotoxic injury and support a role for bFGF signaling in this process.

DOI: 10.1074/jbc.M700678200
PMID: 17556369 [Indexed for MEDLINE]

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