title: Trigeminal uptake and clearance of inhaled manganese chloride in rats and mice.
abstract: Inhaled manganese (Mn) can enter the olfactory bulbs via the olfactory epithelium, and can then be further transported trans-synaptically to deeper brain structures. In addition to olfactory neurons, the nasal cavity is innervated by the maxillary division of the trigeminal nerve that projects to the spinal trigeminal nucleus. Direct uptake and transport of inhaled metal particles in the trigeminal system has not been investigated previously. We studied the uptake, deposition, and clearance of soluble Mn in the trigeminal system following nose-only inhalation of environmentally relevant concentrations. Rats and mice were exposed for 10-days (6 h/day, 5 days/week) to air or MnCl2 aerosols containing 2.3 +/- 1.3 mg/m3 Mn with mass median aerodynamic diameter (MMAD) of 3.1 +/- 1.4 microm for rats and 2.0 +/- 0.09 mg/m3 Mn MnCl2 with MMAD of 1.98 +/- 0.12 microm for mice. Mn concentrations in the trigeminal ganglia and spinal trigeminal nucleus were measured 2 h (0-day), 7-, 14-, or 30-days post-exposure using proton induced X-ray emission (PIXE). Manganese-exposed rats and mice showed statistically elevated levels of Mn in trigeminal ganglia 0-, 7- and 14-days after the 10-days exposure period when compared to control animals. The Mn concentration gradually decreased over time with a clearance rate (t1/2) of 7-8-days. Rats and mice were similar in both average accumulated Mn levels in trigeminal ganglia and in rates of clearance. We also found a small but significant elevation of Mn in the spinal trigeminal nucleus of mice 7-days post-exposure and in rats 0- and 7-days post-exposure. Our data demonstrate that the trigeminal nerve can serve as a pathway for entry of inhaled Mn to the brain in rodents following nose-only exposure and raise the question of whether entry of toxicants via this pathway may contribute to development of neurodegenerative diseases.
authors.affiliation: Community Environmental Health Program, College of Pharmacy, University of New Mexico Health Sciences Center, MSC 9 5360, Albuquerque, NM 87131-0001, USA. jlewis@cybermesa.com
authors.forename: J
authors.initials: J
authors.lastname: Lewis
authors.forename: G
authors.initials: G
authors.lastname: Bench
authors.forename: O
authors.initials: O
authors.lastname: Myers
authors.forename: B
authors.initials: B
authors.lastname: Tinner
authors.forename: W
authors.initials: W
authors.lastname: Staines
authors.forename: E
authors.initials: E
authors.lastname: Barr
authors.forename: K K
authors.initials: KK
authors.lastname: Divine
authors.forename: W
authors.initials: W
authors.lastname: Barrington
authors.forename: J
authors.initials: J
authors.lastname: Karlsson
mesh_terms: D000280:Administration, Inhalation; D000465:Algorithms; D000818:Animals; D002490:Central Nervous System / Q000737:chemistry / Q000378:metabolism; D002712:Chlorides / Q000008:administration & dosage / Q000032:analysis / Q000493:pharmacokinetics*; D005260:Female; D006207:Half-Life; D008297:Male; D017895:Manganese Compounds / Q000008:administration & dosage / Q000032:analysis / Q000493:pharmacokinetics*; D051379:Mice; D051381:Rats; D011916:Rats, Inbred F344; D013045:Species Specificity; D013052:Spectrometry, X-Ray Emission; D012668:Trigeminal Ganglion / Q000737:chemistry / Q000378:metabolism / Q000473:pathology; D014278:Trigeminal Nuclei / Q000737:chemistry / Q000378:metabolism* / Q000473:pathology
chemical_list: D002712:Chlorides; D017895:Manganese Compounds; C025340:manganese chloride