期刊
NEUROBIOLOGY OF DISEASE
卷 37, 期 1, 页码 166-176出版社
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.nbd.2009.09.020
关键词
(Endo)cannabinoids; Excitotoxicity; Multiple sclerosis; UCM707; TMEV
资金
- Spanish Mmisterio de Educacion y Ciencia [SAF 2007/60038]
- Comunidad Autonoma de Madrid (CAM) [S/SAL0261/2006]
- Red espanola de esclerosis multiple (REEM
- RETICS
- ISCIII)
- CONACyT
- Conseil Regional de Basse-Normandie
The 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, PPAR gamma 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. (C) 2009 Elsevier Inc. All rights reserved.
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