title: Manganese uptake and distribution in the brain after methyl bromide-induced lesions in the olfactory epithelia.
abstract: Manganese (Mn) is an essential nutrient with potential neurotoxic effects. Mn deposited in the nose is apparently transported to the brain through anterograde axonal transport, bypassing the blood-brain barrier. However, the role of the olfactory epithelial cells in Mn transport from the nasal cavity to the blood and brain is not well understood. We utilized the methyl bromide (MeBr) lesion model wherein the olfactory epithelium fully regenerates in a time-dependent and cell type-specific manner over the course of 6-8 weeks postinjury. We instilled (54)MnCl(2) intranasally at different recovery periods to study the role of specific olfactory epithelial cell types in Mn transport. (54)MnCl(2) was instilled at 2, 4, 7, 21, and 56 days post-MeBr treatment. (54)Mn concentrations in the blood were measured over the first 4-h period and in the brain and other tissues at 7 days postinstillation. Age-matched control rats were similarly studied at 2 and 56 days. Blood and tissue (54)Mn levels were reduced initially but returned to control values by day 7 post-MeBr exposure, coinciding with the reestablishment of sustentacular cells. Brain (54)Mn levels also decreased but returned to control levels only by 21 days, the period near the completion of neuronal regeneration/bulbar reinnervation. Our data show that Mn transport to the blood and brain temporally correlated with olfactory epithelial regeneration post-MeBr injury. We conclude that (1) sustentacular cells are necessary for Mn transport to the blood and (2) intact axonal projections are required for Mn transport from the nasal cavity to the olfactory bulb and brain.
authors.affiliation: Molecular and Integrative Physiological Sciences Program, Department of Environmental Health, Harvard School of Public Health, Boston, Massachusetts 02115, USA.
authors.forename: Khristy J
authors.initials: KJ
authors.lastname: Thompson
authors.forename: Ramon M
authors.initials: RM
authors.lastname: Molina
authors.forename: Thomas
authors.initials: T
authors.lastname: Donaghey
authors.forename: Sandeep
authors.initials: S
authors.lastname: Savaliya
authors.forename: James E
authors.initials: JE
authors.lastname: Schwob
authors.forename: Joseph D
authors.initials: JD
authors.lastname: Brain
mesh_terms: D000281:Administration, Intranasal; D000375:Aging / Q000097:blood / Q000378:metabolism; D000818:Animals; D001921:Brain / Q000378:metabolism*; D002712:Chlorides / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D006842:Hydrocarbons, Brominated / Q000633:toxicity; D007275:Injections, Intravenous; D008297:Male; D017895:Manganese Compounds / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D009831:Olfactory Mucosa / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012038:Regeneration / Q000502:physiology; D014018:Tissue Distribution
chemical_list: D002712:Chlorides; D006842:Hydrocarbons, Brominated; D017895:Manganese Compounds; C005218:methyl bromide; C025340:manganese chloride