title: Alteration of the endocannabinoid system in mouse brain during prion disease.
abstract: Prion diseases are neurodegenerative disorders characterized by deposition of the pathological prion protein (PrPsc) within the brain of affected humans and animals. Microglial cell activation is a common feature of prion diseases; alterations of various neurotransmitter systems and neurotransmission have been also reported. Owing to its ability to modulate both neuroimmune responses and neurotransmission, it was of interest to study the brain endocannabinoid system in a prion-infected mouse model. The production of the endocannabinoid, 2-arachidonoyglycerol (2-AG), was enhanced 10 weeks post-infection, without alteration of the other endocannabinoid, anandamide. The CB2 receptor expression was up-regulated in brains of prion-infected mice as early as 10 weeks and up to 32 weeks post-infection whereas the mRNAs of other cannabinoid receptors (CBRs) remain unchanged. The observed alterations of the endocannabinoid system were specific for prion infection since no significant changes were observed in the brain of prion-resistant mice, that is, mice devoid of the Prnp gene. Our study highlights important alterations of the endocannabinoid system during early stages of the disease long before the clinical signs of the disease.
authors.affiliation: Endocannabinoid Research Group, Istituto di Chimica Biomolecolare, CNR Via Campi Flegrei 34, Comprensorio Olivetti, 80078 Pozzuoli (NA), Italy.
authors.forename: S
authors.initials: S
authors.lastname: Petrosino
authors.forename: B
authors.initials: B
authors.lastname: Ménard
authors.forename: N
authors.initials: N
authors.lastname: Zsürger
authors.forename: V
authors.initials: V
authors.lastname: Di Marzo
authors.forename: J
authors.initials: J
authors.lastname: Chabry
mesh_terms: D000818:Animals; D001095:Arachidonic Acids / Q000378:metabolism; D001927:Brain Diseases / Q000378:metabolism* / Q000473:pathology; D063385:Cannabinoid Receptor Modulators / Q000378:metabolism*; D002460:Cell Line; D002478:Cells, Cultured; D004195:Disease Models, Animal; D063388:Endocannabinoids; D005989:Glycerides / Q000378:metabolism; D051379:Mice; D057507:Mice, 129 Strain; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D017096:Prion Diseases / Q000378:metabolism* / Q000473:pathology*; D043885:Receptor, Cannabinoid, CB2 / Q000235:genetics / Q000378:metabolism; D043882:Receptors, Cannabinoid / Q000235:genetics / Q000378:metabolism*; D015854:Up-Regulation / Q000502:physiology
chemical_list: D001095:Arachidonic Acids; D063385:Cannabinoid Receptor Modulators; D063388:Endocannabinoids; D005989:Glycerides; D043885:Receptor, Cannabinoid, CB2; D043882:Receptors, Cannabinoid; C094503:glyceryl 2-arachidonate