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An endocannabinoid tone limits excitotoxicity in vitro and in a model of multiple sclerosis.
- Source :
-
Neurobiology of disease [Neurobiol Dis] 2010 Jan; Vol. 37 (1), pp. 166-76. Date of Electronic Publication: 2009 Oct 06. - Publication Year :
- 2010
-
Abstract
- 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 CB(1) and CB(2) cannabinoid receptors, as well as the nuclear factor, PPARgamma. 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.
- Subjects :
- Animals
Arachidonic Acids pharmacology
Astrocytes drug effects
Astrocytes metabolism
Cells, Cultured
Cerebral Cortex drug effects
Cerebral Cortex metabolism
Disease Models, Animal
Excitatory Amino Acid Transporter 2 metabolism
Female
Furans pharmacology
Mice
Mice, Inbred Strains
Mice, Knockout
N-Methylaspartate toxicity
Neuroprotective Agents pharmacology
PPAR gamma metabolism
Polyunsaturated Alkamides pharmacology
Receptor, Cannabinoid, CB1 genetics
Receptor, Cannabinoid, CB1 metabolism
Receptor, Cannabinoid, CB2 metabolism
alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid toxicity
Cannabinoid Receptor Modulators metabolism
Endocannabinoids
Multiple Sclerosis drug therapy
Multiple Sclerosis metabolism
Neurons drug effects
Neurons metabolism
Neurotoxins toxicity
Subjects
Details
- Language :
- English
- ISSN :
- 1095-953X
- Volume :
- 37
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- Neurobiology of disease
- Publication Type :
- Academic Journal
- Accession number :
- 19815071
- Full Text :
- https://doi.org/10.1016/j.nbd.2009.09.020