2024-03-29T16:02:22Zhttp://digital.csic.es/dspace-oai/requestoai:digital.csic.es:10261/664812022-04-19T06:47:39Zcom_10261_54com_10261_1col_10261_307
An endocannabinoid tone limits excitotoxicity in vitro and in a model of multiple sclerosis
Loría, Frida
Petrosino, S.
Hernangómez-Herrero, Miriam
Mestre, Leyre
Spagnolo, Alessandra
Correa, Fernando Gabriel
Di Marzo, Vincenzo
Docagne, Fabian
Guaza, Carmen
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, 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.
2013-02-12T09:50:28Z
2013-02-12T09:50:28Z
2010-01
2013-02-12T09:50:28Z
artículo
Neurobiology of Disease 37(1): 166-176 (2010)
http://hdl.handle.net/10261/66481
10.1016/j.nbd.2009.09.020
eng
http://doi.org/10.1016/j.nbd.2009.09.020
closedAccess
Academic Press