Cannabinoid CB1 receptors regulate neuronal TNF-α effects in experimental autoimmune encephalomyelitis.

6533b82afe1ef96bd128c1de

RESEARCH PRODUCT

Cannabinoid CB1 receptors regulate neuronal TNF-α effects in experimental autoimmune encephalomyelitis.

Silvia Rossi Francesca Cavasinni Beat Lutz Luca Muzio Valeria Studer Alessandra Musella Caterina Motta Valentina De Chiara Gianvito Martino Giorgio Bernardi Roberto Furlan Diego Centonze Benjamin F. Cravatt Mauro Maccarrone

subject

Cannabinoid receptor Encephalomyelitis Autoimmune Experimental Polyunsaturated Alkamides medicine.medical_treatment Immunology Excitotoxicity Glutamic Acid Arachidonic Acids Pharmacology Biology medicine.disease_cause Receptors N-Methyl-D-Aspartate Receptors Tumor Necrosis Factor Amidohydrolases Etanercept Behavioral Neuroscience chemistry.chemical_compound Mice Receptor Cannabinoid CB1 Fatty acid amide hydrolase Cannabinoid Receptor Modulators medicine Animals Dronabinol Receptors AMPA 6-Cyano-7-nitroquinoxaline-2 3-dione Mice Knockout Neurons Endocrine and Autonomic Systems Tumor Necrosis Factor-alpha Neurodegeneration Experimental autoimmune encephalomyelitis Excitatory Postsynaptic Potentials Anandamide medicine.disease Endocannabinoid system Corpus Striatum Mice Inbred C57BL chemistry Immunoglobulin G Immunology Nerve Degeneration Settore MED/26 - Neurologia Female Cannabinoid Dizocilpine Maleate Endocannabinoids

description

Abstract Cannabinoid CB1 receptors (CB1Rs) regulate the neurodegenerative damage of experimental autoimmune encephalomyelitis (EAE) and of multiple sclerosis (MS). The mechanism by which CB1R stimulation exerts protective effects is still unclear. Here we show that pharmacological activation of CB1Rs dampens the tumor necrosis factor α (TNFα)-mediated potentiation of striatal spontaneous glutamate-mediated excitatory postsynaptic currents (EPSCs), which is believed to cogently contribute to the inflammation-induced neurodegenerative damage observed in EAE mice. Furthermore, mice lacking CB1Rs showed a more severe clinical course and, in parallel, exacerbated alterations of sEPSC duration after induction of EAE, indicating that endogenous cannabinoids activate CB1Rs and mitigate the synaptotoxic action of TNFα in EAE. Consistently, we found that mice lacking the fatty acid amide hydrolase (FAAH), and thus expressing abnormally high brain levels of the endocannabinoid anandamide, developed a less severe EAE associated with preserved TNFα-induced sEPSC alterations. CB1Rs are important modulators of EAE pathophysiology, and might play a mechanistic role in the neurodegenerative damage of MS patients.

year	journal	country	edition	language
2011-08-01	Brain, behavior, and immunity

10.1016/j.bbi.2011.03.017 https://pubmed.ncbi.nlm.nih.gov/21473912