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

F. Loría; S. Petrosino; M. Hernangómez; L. Mestre; A. Spagnolo; F. Correa; V. Di Marzo; F. Docagne; C. Guaza

Neurobiology of Disease (Jan 2010)

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

F. Loría,
S. Petrosino,
M. Hernangómez,
L. Mestre,
A. Spagnolo,
F. Correa,
V. Di Marzo,
F. Docagne,
C. Guaza

Affiliations

F. Loría: Neuroimmunology Group, Department of Functional and Systems Neurobiology, Instituto Cajal, Consejo Superior de Investigaciones Científicas, Madrid, Spain
S. Petrosino: Endocannabinoid Research Group, Institute of Biomolecular Chemistry, Consiglio Nazionale delle Ricerche, Pozzuoli (Napoli), Italy
M. Hernangómez: Neuroimmunology Group, Department of Functional and Systems Neurobiology, Instituto Cajal, Consejo Superior de Investigaciones Científicas, Madrid, Spain
L. Mestre: Neuroimmunology Group, Department of Functional and Systems Neurobiology, Instituto Cajal, Consejo Superior de Investigaciones Científicas, Madrid, Spain
A. Spagnolo: Neuroimmunology Group, Department of Functional and Systems Neurobiology, Instituto Cajal, Consejo Superior de Investigaciones Científicas, Madrid, Spain
F. Correa: Neuroimmunology Group, Department of Functional and Systems Neurobiology, Instituto Cajal, Consejo Superior de Investigaciones Científicas, Madrid, Spain
V. Di Marzo: Endocannabinoid Research Group, Institute of Biomolecular Chemistry, Consiglio Nazionale delle Ricerche, Pozzuoli (Napoli), Italy; Corresponding authors. F. Docagne is to be contacted at INSERM U919 “Serine proteases and pathophysiology of the neurovascular unit” Centre Cyceron, Bd H Becquerel, BP 5229, 14074 Caen, France. Fax: +33 231 47 02 22. V. Di Marzo, Endocannabinoid Research Group, Institute of Biomolecular Chemistry, Consiglio Nazionale delle Ricerche, Pozzuoli (Napoli), Italy. Fax: +39 081 8041770.
F. Docagne: Neuroimmunology Group, Department of Functional and Systems Neurobiology, Instituto Cajal, Consejo Superior de Investigaciones Científicas, Madrid, Spain; INSERM U919 “Serine proteases and pathophysiology of the neurovascular unit,” UMR CINAPS–CNRS/CEA/UCBN/Université Paris Descartes, Caen, France; Corresponding authors. F. Docagne is to be contacted at INSERM U919 “Serine proteases and pathophysiology of the neurovascular unit” Centre Cyceron, Bd H Becquerel, BP 5229, 14074 Caen, France. Fax: +33 231 47 02 22. V. Di Marzo, Endocannabinoid Research Group, Institute of Biomolecular Chemistry, Consiglio Nazionale delle Ricerche, Pozzuoli (Napoli), Italy. Fax: +39 081 8041770.
C. Guaza: Neuroimmunology Group, Department of Functional and Systems Neurobiology, Instituto Cajal, Consejo Superior de Investigaciones Científicas, Madrid, Spain

Journal volume & issue: Vol. 37, no. 1
pp. 166 – 176

Abstract

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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.

Published in Neurobiology of Disease

ISSN: 0969-9961 (Print); 1095-953X (Online)
Publisher: Elsevier
Country of publisher: United States
LCC subjects: Medicine: Internal medicine: Neurosciences. Biological psychiatry. Neuropsychiatry
Website: https://www.journals.elsevier.com/neurobiology-of-disease

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