Please use this identifier to cite or link to this item: http://hdl.handle.net/10261/66481
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Title

An endocannabinoid tone limits excitotoxicity in vitro and in a model of multiple sclerosis

AuthorsLoría, Frida CSIC ORCID; Petrosino, S.; Hernangómez-Herrero, Miriam CSIC; Mestre, Leyre CSIC ORCID ; Spagnolo, Alessandra; Correa, Fernando Gabriel CSIC; Di Marzo, V.; Docagne, Fabian CSIC ORCID; Guaza, Carmen CSIC ORCID
Issue DateJan-2010
PublisherAcademic Press
CitationNeurobiology of Disease 37(1): 166-176 (2010)
AbstractThe aim of this study was to evaluate how endocannabinoids interact with excitotoxic processes both in vitro, using primary neural cell cultures, and in vivo, in the TMEV-IDD model of multiple sclerosis. First, we observed that neuronal cells respond to excitotoxic challenges by the production of endocannabinoid molecules which in turn exerted neuroprotective effects against excitotoxicity. The inhibitor of endocannabinoid uptake, UCM707, protected specifically against AMPA-induced excitotoxicity, by activating CB1 and CB2 cannabinoid receptors, as well as the nuclear factor, PPARγ. This neuroprotective effect was reverted by blocking the glial glutamate transporter, GLT-1. Mice subjected to the model of multiple sclerosis showed a decrease in the expression of GLT-1. UCM707 reversed this loss of GLT-1 and induced a therapeutic effect. Our data indicate that the enhancement of the endocannabinoid tone leads to neuroprotection against AMPA-induced excitotoxicity and provides therapeutic effects in this model of multiple sclerosis. © 2009 Elsevier Inc. All rights reserved.
Publisher version (URL)http://doi.org/10.1016/j.nbd.2009.09.020
URIhttp://hdl.handle.net/10261/66481
DOI10.1016/j.nbd.2009.09.020
Identifiersdoi: 10.1016/j.nbd.2009.09.020
issn: 0969-9961
Appears in Collections:(IC) Artículos

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