title: Brain CB₁ receptor expression following lipopolysaccharide-induced inflammation.
abstract: Cannabinoid 1 receptors (CB(1)) are highly expressed on presynaptic terminals in the brain where they are importantly involved in the control of neurotransmitter release. Alteration of CB(1) expression is associated with a variety of neurological and psychiatric disorders. There is now compelling evidence that peripheral inflammatory disorders are associated with depression and cognitive impairments. These can be modeled in rodents with peripheral administration of lipopolysaccharide (LPS), but central effects of this treatment remain to be fully elucidated. As a reduction in endocannabinoid tone is thought to contribute to depression, we asked whether the expression of CB(1) in the CNS is altered following LPS treatment. CD1 mice received LPS (0.1-1mg/kg, ip) and 6h later activated microglial cells were observed only in circumventricular organs and only at the higher dose. At 24h, activated microglial cells were identified in other brain regions, including the hippocampus, a structure implicated in some mood disorders. Immunohistochemistry and real-time polymerase chain reaction (PCR) were utilized to evaluate the change of CB(1) expression 24h after inflammation. LPS induced an increase of CB(1) mRNA in the hippocampus and brainstem. Subsequent immunohistochemical analysis revealed reduced CB(1) in the hippocampus, especially in CA3 pyramidal layer. Analysis of co-localization with markers of excitatory and inhibitory terminals indicated that the decrease in CB(1) expression was restricted to glutamatergic terminals. Despite widespread microglial activation, these results suggest that peripheral LPS treatment leads to limited changes in CB(1) expression in the brain.
authors.affiliation: Hotchkiss Brain Institute, Department of Physiology and Pharmacology, University of Calgary, Calgary, Alberta, Canada T2N 4N1.
authors.forename: H
authors.initials: H
authors.lastname: Hu
authors.forename: W
authors.initials: W
authors.lastname: Ho
authors.forename: K
authors.initials: K
authors.lastname: Mackie
authors.forename: Q J
authors.initials: QJ
authors.lastname: Pittman
authors.forename: K A
authors.initials: KA
authors.lastname: Sharkey
mesh_terms: D000818:Animals; D001921:Brain / Q000187:drug effects / Q000378:metabolism*; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D005786:Gene Expression Regulation / Q000187:drug effects* / Q000235:genetics; D005968:Glutamate Decarboxylase / Q000378:metabolism; D007249:Inflammation / Q000139:chemically induced* / Q000473:pathology*; D008070:Lipopolysaccharides / Q000633:toxicity*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D012333:RNA, Messenger / Q000378:metabolism; D043884:Receptor, Cannabinoid, CB1 / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D013997:Time Factors; D050598:Vesicular Glutamate Transport Protein 1 / Q000378:metabolism
chemical_list: D008070:Lipopolysaccharides; D012333:RNA, Messenger; D043884:Receptor, Cannabinoid, CB1; D050598:Vesicular Glutamate Transport Protein 1; D005968:Glutamate Decarboxylase; C401141:glutamate decarboxylase 2