Translocation of inhaled ultrafine manganese oxide particles to the central nervous system

Alison Elder, Robert Gelein, Vanessa Silva, Tessa Feikert, Lisa Opanashuk, Janet Carter, Russell Potter, Andrew Maynard, Yasuo Ito, Jacob Finkelstein, Günter Oberdörster

Research output: Contribution to journalArticle

686 Citations (Scopus)

Abstract

Background: Studies in monkeys with intranasally instilled gold ultrafine particles (UFPs; <100 nm) and in rats with inhaled carbon UFPs suggested that solid UFPs deposited in the nose travel along the olfactory nerve to the olfactory bulb. Methods: To determine if olfactory translocation occuss for other solid metal UFPs and assess potential health effects, we exposed groups of rats to manganese (Mn) oxide UFPs (30 nm; - 500 μg/m3) with either both nostrils patent or the right nostril occluded. We analyzed Mn in lung, liver, olfactory bulb, and other brain regions, and we performed gene and protein analyses. Results: After 12 days of exposure with both nostrils patent, Mn concentrations in the olfactory bulb increased 3.5-fold, whereas lung Mn concentrations doubled; the were also increase in striatum, frontal cortex, and cerebellum. Lung lavage analysis showed no indications of lung inflammation, whereas increases in olfactory bulb tumor necrosis factor-α mRNA (- 8-fold) and protein (- 30-fold) were foung after 11 days of exposure and, to a lesser degree, in other brain regions with increased Mn levels. Macrophage inflammatory protein-2, glial fibrillary acidic protein, and neuronal cell adhesion molecule mRNA were also increased in olfactory bulb. With the right nostril occluded for a 2-day exposure, Mn accumulated only in the left olfactory bulb. Solubilization of the Mn oxide UFps was <1.5% per day. Conclusions: We conclude that the olfactory neuronal pathway is efficient for transcolating inhaled Mn oxide as solid UFPs to the central nervous system and that this can result in inflammatory changes. We suggest that despite differences between human and rodent olfactory systems, this pathway is relevant in humans.

Original languageEnglish (US)
Pages (from-to)1172-1178
Number of pages7
JournalEnvironmental Health Perspectives
Volume114
Issue number8
DOIs
StatePublished - Aug 2006
Externally publishedYes

Fingerprint

Olfactory Bulb
manganese oxide
Neurology
nervous system
Manganese
translocation
manganese
Central Nervous System
protein
Olfactory Pathways
fold
brain
Rats
Brain
Neuronal Cell Adhesion Molecules
Chemokine CXCL2
Messenger RNA
Olfactory Nerve
Glial Fibrillary Acidic Protein
solubilization

Keywords

  • Brain
  • Central nervous system
  • CNS
  • Inhalation
  • Intranasal instillation
  • Manganese
  • Metals
  • Nose
  • Olfactory bulb
  • Respiratory tract

ASJC Scopus subject areas

  • Environmental Science(all)
  • Environmental Chemistry
  • Public Health, Environmental and Occupational Health

Cite this

Elder, A., Gelein, R., Silva, V., Feikert, T., Opanashuk, L., Carter, J., ... Oberdörster, G. (2006). Translocation of inhaled ultrafine manganese oxide particles to the central nervous system. Environmental Health Perspectives, 114(8), 1172-1178. https://doi.org/10.1289/ehp.9030

Translocation of inhaled ultrafine manganese oxide particles to the central nervous system. / Elder, Alison; Gelein, Robert; Silva, Vanessa; Feikert, Tessa; Opanashuk, Lisa; Carter, Janet; Potter, Russell; Maynard, Andrew; Ito, Yasuo; Finkelstein, Jacob; Oberdörster, Günter.

In: Environmental Health Perspectives, Vol. 114, No. 8, 08.2006, p. 1172-1178.

Research output: Contribution to journalArticle

Elder, A, Gelein, R, Silva, V, Feikert, T, Opanashuk, L, Carter, J, Potter, R, Maynard, A, Ito, Y, Finkelstein, J & Oberdörster, G 2006, 'Translocation of inhaled ultrafine manganese oxide particles to the central nervous system', Environmental Health Perspectives, vol. 114, no. 8, pp. 1172-1178. https://doi.org/10.1289/ehp.9030
Elder, Alison ; Gelein, Robert ; Silva, Vanessa ; Feikert, Tessa ; Opanashuk, Lisa ; Carter, Janet ; Potter, Russell ; Maynard, Andrew ; Ito, Yasuo ; Finkelstein, Jacob ; Oberdörster, Günter. / Translocation of inhaled ultrafine manganese oxide particles to the central nervous system. In: Environmental Health Perspectives. 2006 ; Vol. 114, No. 8. pp. 1172-1178.
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abstract = "Background: Studies in monkeys with intranasally instilled gold ultrafine particles (UFPs; <100 nm) and in rats with inhaled carbon UFPs suggested that solid UFPs deposited in the nose travel along the olfactory nerve to the olfactory bulb. Methods: To determine if olfactory translocation occuss for other solid metal UFPs and assess potential health effects, we exposed groups of rats to manganese (Mn) oxide UFPs (30 nm; - 500 μg/m3) with either both nostrils patent or the right nostril occluded. We analyzed Mn in lung, liver, olfactory bulb, and other brain regions, and we performed gene and protein analyses. Results: After 12 days of exposure with both nostrils patent, Mn concentrations in the olfactory bulb increased 3.5-fold, whereas lung Mn concentrations doubled; the were also increase in striatum, frontal cortex, and cerebellum. Lung lavage analysis showed no indications of lung inflammation, whereas increases in olfactory bulb tumor necrosis factor-α mRNA (- 8-fold) and protein (- 30-fold) were foung after 11 days of exposure and, to a lesser degree, in other brain regions with increased Mn levels. Macrophage inflammatory protein-2, glial fibrillary acidic protein, and neuronal cell adhesion molecule mRNA were also increased in olfactory bulb. With the right nostril occluded for a 2-day exposure, Mn accumulated only in the left olfactory bulb. Solubilization of the Mn oxide UFps was <1.5{\%} per day. Conclusions: We conclude that the olfactory neuronal pathway is efficient for transcolating inhaled Mn oxide as solid UFPs to the central nervous system and that this can result in inflammatory changes. We suggest that despite differences between human and rodent olfactory systems, this pathway is relevant in humans.",
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AU - Carter, Janet

AU - Potter, Russell

AU - Maynard, Andrew

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KW - Respiratory tract

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