title: Effect of manganese treatment on the accumulation on biologically relevant metals in rat cochlea and brain by inductively coupled plasma mass spectrometry.
abstract: Manganese (Mn), iron (Fe), zinc (Zn), and copper (Cu) are essential transitions metals that are required in trace amounts, however chronic exposure to high concentrations can cause severe and irreversible neurotoxicity. Since prolonged exposure to Mn leads to manganism, a disorder exhibiting a diverse array of neurological impairments progressing to a debilitating and irreversible extrapyramidal condition symptomatically similar to Parkinson's disease, we measured the concentration of Mn as well as Fe, Zn and Cu in three region of the brain (globus pallidus, striatum and inferior colliculus) and three regions in the cochlea (stria vascularis, basilar membrane and modiolus) under normal conditions or after 30 or 60 days of oral administration of Mn (10 mg/ml ad libitum). Under normal conditions, Mn, Zn and Fe were typically higher in the cochlea than in the three brain regions whereas Cu was equal to or lower. Oral treatment with Mn for 30 or 60 days resulted in 20-75 % increases in Mn concentrations in both cochlea and brain samples, but had little effect on Cu and Fe levels. In contrast, Zn levels decreased (20-80 %) with Mn exposure. Our results show for the first time how prolonged oral Mn-ingestion affects the concentration of Mn, Cu, Zn and Fe, in the three regions of the cochlea, the inferior colliculus in auditory midbrain and the striatum and globus pallidus, two regions implicated in Parkinson's disorder. The Mn-induced changes in the concentration of Mn, Cu, Zn and Fe may provide new insights relevant to the neurotoxicity of Mn and the transport and accumulation of these metals in cochlea and brain.
authors.affiliation: Department of Chemistry, University at Buffalo, Buffalo, NY, 14260, USA. ejmullin@buffalo.edu.
authors.forename: Elizabeth J
authors.initials: EJ
authors.lastname: Mullin
authors.affiliation: Department of Chemistry, University at Buffalo, Buffalo, NY, 14260, USA. srwegst@buffalo.edu.
authors.forename: Stacia R
authors.initials: SR
authors.lastname: Wegst-Uhrich
authors.affiliation: Department of Communicative Disorders and Sciences, University at Buffalo, Buffalo, NY, 14214, USA. dding@acsu.buffalo.edu.|Department of Otolaryngology Head and Neck Surgery, Xiangya Hospital, Central South University, Changsha, 410008, Hunan, China. dding@acsu.buffalo.edu.
authors.forename: Dalian
authors.initials: D
authors.lastname: Ding
authors.affiliation: Center for Hearing and Deafness, University at Buffalo, Buffalo, NY, 14214, USA. smanohar@buffalo.edu.
authors.forename: Senthilvelan
authors.initials: S
authors.lastname: Manohar
authors.affiliation: Center for Hearing and Deafness, University at Buffalo, Buffalo, NY, 14214, USA. vijayapr@buffalo.edu.
authors.forename: Vijaya Prakash
authors.initials: VP
authors.lastname: Krishnan Muthaiah
authors.affiliation: Department of Communicative Disorders and Sciences, University at Buffalo, Buffalo, NY, 14214, USA. salvi@buffalo.edu.
authors.forename: Richard
authors.initials: R
authors.lastname: Salvi
authors.affiliation: Department of Chemistry, University at Buffalo, Buffalo, NY, 14260, USA. dianaaga@buffalo.edu.
authors.forename: Diana S
authors.initials: DS
authors.lastname: Aga
authors.affiliation: Department of Pharmacology and Toxicology, University at Buffalo, 11 Cary Hall, Buffalo, NY, 14214, USA. jaroth@buffalo.edu.
authors.forename: Jerome A
authors.initials: JA
authors.lastname: Roth
mesh_terms: D000284:Administration, Oral; D000818:Animals; D002413:Cations, Divalent; D002712:Chlorides / Q000494:pharmacology*; D003051:Cochlea / Q000187:drug effects* / Q000378:metabolism; D003300:Copper / Q000378:metabolism*; D003342:Corpus Striatum / Q000187:drug effects / Q000378:metabolism; D005260:Female; D005917:Globus Pallidus / Q000187:drug effects / Q000378:metabolism; D007245:Inferior Colliculi / Q000187:drug effects / Q000378:metabolism; D017136:Ion Transport; D007501:Iron / Q000378:metabolism*; D017895:Manganese Compounds / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013054:Spectrophotometry, Atomic; D015032:Zinc / Q000378:metabolism*
chemical_list: D002413:Cations, Divalent; D002712:Chlorides; D017895:Manganese Compounds; D003300:Copper; D007501:Iron; D015032:Zinc; C025340:manganese chloride
keywords: Cochlea; Copper; ICP-MS; Iron; Manganese; Trace analysis; Zinc