title: An endocannabinoid system is present in the mouse olfactory epithelium but does not modulate olfaction.
abstract: Endocannabinoids modulate a diverse array of functions including progenitor cell proliferation in the central nervous system, and odorant detection and food intake in the mammalian central olfactory system and larval Xenopus laevis peripheral olfactory system. However, the presence and role of endocannabinoids in the peripheral olfactory epithelium have not been examined in mammals. We found the presence of cannabinoid type 1 (CB1) and cannabinoid type 2 (CB2) receptor protein and mRNA in the olfactory epithelium. Using either immunohistochemistry or calcium imaging we localized CB1 receptors on neurons, glia-like sustentacular cells, microvillous cells and progenitor-like basal cells. To examine the role of endocannabinoids, CB1- and CB2- receptor-deficient (CB1(-/-)/CB2(-/-)) mice were used. The endocannabinoid 2-arachidonylglycerol (2-AG) was present at high levels in both C57BL/6 wildtype and CB1(-/-)/CB2(-/-) mice. 2-AG synthetic and degradative enzymes are expressed in wildtype mice. A small but significant decrease in basal cell and olfactory sensory neuron numbers was observed in CB1(-/-)/CB2(-/-) mice compared to wildtype mice. The decrease in olfactory sensory neurons did not translate to impairment in olfactory-mediated behaviors assessed by the buried food test and habituation/dishabituation test. Collectively, these data indicate the presence of an endocannabinoid system in the mouse olfactory epithelium. However, unlike in tadpoles, endocannabinoids do not modulate olfaction. Further investigation on the role of endocannabinoids in progenitor cell function in the olfactory epithelium is warranted.
authors.affiliation: Neuroscience Program, Michigan State University, 293 Farm Lane, East Lansing, MI 48824, USA; Environmental and Integrative Toxicological Sciences, Michigan State University, 1129 Farm Lane, East Lansing, MI 48824, USA. Electronic address: hutchche@umich.edu.
authors.forename: C R
authors.initials: CR
authors.lastname: Hutch
authors.affiliation: Department of Pharmacology and Toxicology, Medical College of Wisconsin, 8701 Watertown Plank Road, Milwaukee, WI 53226, USA. Electronic address: chillard@mcw.edu.
authors.forename: C J
authors.initials: CJ
authors.lastname: Hillard
authors.affiliation: Department of Pharmacology and Toxicology, Michigan State University, 1355 Bogue Street, East Lansing, MI 48824, USA. Electronic address: JIAC01@mail.etsu.edu.
authors.forename: C
authors.initials: C
authors.lastname: Jia
authors.affiliation: Neuroscience Program, Michigan State University, 293 Farm Lane, East Lansing, MI 48824, USA; Environmental and Integrative Toxicological Sciences, Michigan State University, 1129 Farm Lane, East Lansing, MI 48824, USA; Department of Pharmacology and Toxicology, Michigan State University, 1355 Bogue Street, East Lansing, MI 48824, USA. Electronic address: hegg@msu.edu.
authors.forename: C C
authors.initials: CC
authors.lastname: Hegg
mesh_terms: D000818:Animals; D001095:Arachidonic Acids / Q000378:metabolism*; D063388:Endocannabinoids / Q000378:metabolism*; D005989:Glycerides / Q000378:metabolism*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009831:Olfactory Mucosa / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D018034:Olfactory Receptor Neurons / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D043884:Receptor, Cannabinoid, CB1 / Q000235:genetics / Q000378:metabolism*; D043885:Receptor, Cannabinoid, CB2 / Q000235:genetics / Q000378:metabolism*; D012903:Smell / Q000502:physiology*; D046509:Tissue Culture Techniques
chemical_list: D001095:Arachidonic Acids; C578453:CNR1 protein, mouse; C571431:Cnr2 protein, mouse; D063388:Endocannabinoids; D005989:Glycerides; D012333:RNA, Messenger; D043884:Receptor, Cannabinoid, CB1; D043885:Receptor, Cannabinoid, CB2; C094503:glyceryl 2-arachidonate
keywords: 2-AG; cannabinoids; olfaction; progenitor cells