title: Genetic deletion of Fatty Acid Amide Hydrolase results in improved long-term outcome in chronic autoimmune encephalitis.
abstract: The enzyme Fatty Acid Amide Hydrolase (FAAH) is a key regulator of the endogenous levels of a family of biologically active lipid mediators, the fatty acid amides. These include anandamide, oleoyl ethanolamide and palmitoyl ethanolamide, and their effects are mediated by a variety of downstream targets including cannabinoid receptors and peroxisome proliferator-activated receptors (PPARs). Activation of both of these may have anti-inflammatory and neuroprotective effects. Levels of all three mediators are low in normal nervous tissue, but substantially elevated in mice lacking FAAH as a result of genetic deletion. There is a long anecdotal history of cannabis use by patients suffering from multiple sclerosis, and preclinical studies have indicated beneficial effects of cannabinoid receptor stimulation on both long-term outcome and acute muscle spasm in rodent models of multiple sclerosis (experimental autoimmune encephalitis; EAE). Thus far no report has appeared on the effect of inhibition of FAAH on the progression of EAE. Using a chronic mouse EAE model, we present data indicating that mice lacking FAAH experience an initial inflammatory phase of EAE similar in severity to wild type controls, but exhibited a more substantial clinical remission compared to wild type mice.
authors.affiliation: Johnson & Johnson Pharmaceutical Research & Development, L.L.C., 3210 Merryfield Row, San Diego, CA 92121, United States. mwebb5@prdus.jnj.com
authors.forename: Michael
authors.initials: M
authors.lastname: Webb
authors.forename: Lin
authors.initials: L
authors.lastname: Luo
authors.forename: Jing Ying
authors.initials: JY
authors.lastname: Ma
authors.forename: Chui-Se
authors.initials: CS
authors.lastname: Tham
mesh_terms: D000581:Amidohydrolases / Q000172:deficiency*; D000818:Animals; D017252:CD3 Complex / Q000378:metabolism; D002908:Chronic Disease; D003711:Demyelinating Diseases / Q000209:etiology; D004195:Disease Models, Animal; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000139:chemically induced / Q000235:genetics* / Q000473:pathology / Q000503:physiopathology*; D006023:Glycoproteins; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D063308:Myelin-Oligodendrocyte Glycoprotein; D010446:Peptide Fragments; D013116:Spinal Cord / Q000473:pathology; D013601:T-Lymphocytes / Q000473:pathology / Q000502:physiology; D013997:Time Factors; D000099252:Fatty Acid Amide Hydrolases
chemical_list: D000581:Amidohydrolases; D017252:CD3 Complex; D006023:Glycoproteins; D063308:Myelin-Oligodendrocyte Glycoprotein; D010446:Peptide Fragments; D000099252:Fatty Acid Amide Hydrolases; C445081:myelin oligodendrocyte glycoprotein (35-55)