Subchronic, Low-Level Intraperitoneal Injections of Manganese (IV) Oxide and Manganese (II) Chloride Affect Rat Brain Neurochemistry

Brian S. Nielsen, Erik Huusfeldt Larsen, Ole Ladefoged, Henrik Rye Lam

Research output: Contribution to journalJournal articleResearchpeer-review

Abstract

Manganese (Mn) is neurotoxic and can induce manganism, a Parkinson-like disease categorized as being a serious central nervous system irreversible neurodegenerative disease. An increased risk of developing symptoms of Parkinson disease has been linked to work-related exposure, for example, for workers in agriculture, horticulture, and people living near areas with frequent use of Mn-containing pesticides. In this study, the focus was placed on neurochemical effects of Mn. Rats were dosed intraperitoneally with 0.9% NaCl (control), 1.22 mg Mn (as MnO2)/kg bodyweight (bw)/day, or 2.5 mg Mn (as MnCl2)/kg bw/day for 7 d/wk for 8 or 12 weeks. This dosing regimen adds relevant new knowledge about Mn neurotoxicity as a consequence of low-dose subchronic Mn dosing. Manganese concentrations increased in the striatum, the rest of the brain, and in plasma, and regional brain neurotransmitter concentrations, including noradrenaline, dopamine (DA), 5-hydroxytrytamine, glutamate, taurine, and γ-amino butyric acid, and the activity of acetylcholinesterase changed. Importantly, a target parameter for Parkinson disease and manganism, the striatal DA concentration, was reduced after 12 weeks of dosing with MnCl2. Plasma prolactin concentration was not significantly affected due to a potentially reduced dopaminergic inhibition of the prolactin release from the anterior hypophysis. No effects on the striatal α-synuclein and synaptophysin protein levels were detected.
Original languageEnglish
JournalInternational Journal of Toxicology
Volume36
Issue number3
Pages (from-to)239-251
ISSN1091-5818
DOIs
Publication statusPublished - 2017

Keywords

  • Parkinson’s disease
  • manganese
  • manganese speciation
  • manganism
  • neurotoxicity
  • subchronic

Cite this

Nielsen, Brian S. ; Larsen, Erik Huusfeldt ; Ladefoged, Ole ; Lam, Henrik Rye. / Subchronic, Low-Level Intraperitoneal Injections of Manganese (IV) Oxide and Manganese (II) Chloride Affect Rat Brain Neurochemistry. In: International Journal of Toxicology. 2017 ; Vol. 36, No. 3. pp. 239-251.
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title = "Subchronic, Low-Level Intraperitoneal Injections of Manganese (IV) Oxide and Manganese (II) Chloride Affect Rat Brain Neurochemistry",
abstract = "Manganese (Mn) is neurotoxic and can induce manganism, a Parkinson-like disease categorized as being a serious central nervous system irreversible neurodegenerative disease. An increased risk of developing symptoms of Parkinson disease has been linked to work-related exposure, for example, for workers in agriculture, horticulture, and people living near areas with frequent use of Mn-containing pesticides. In this study, the focus was placed on neurochemical effects of Mn. Rats were dosed intraperitoneally with 0.9{\%} NaCl (control), 1.22 mg Mn (as MnO2)/kg bodyweight (bw)/day, or 2.5 mg Mn (as MnCl2)/kg bw/day for 7 d/wk for 8 or 12 weeks. This dosing regimen adds relevant new knowledge about Mn neurotoxicity as a consequence of low-dose subchronic Mn dosing. Manganese concentrations increased in the striatum, the rest of the brain, and in plasma, and regional brain neurotransmitter concentrations, including noradrenaline, dopamine (DA), 5-hydroxytrytamine, glutamate, taurine, and γ-amino butyric acid, and the activity of acetylcholinesterase changed. Importantly, a target parameter for Parkinson disease and manganism, the striatal DA concentration, was reduced after 12 weeks of dosing with MnCl2. Plasma prolactin concentration was not significantly affected due to a potentially reduced dopaminergic inhibition of the prolactin release from the anterior hypophysis. No effects on the striatal α-synuclein and synaptophysin protein levels were detected.",
keywords = "Parkinson’s disease, manganese, manganese speciation, manganism, neurotoxicity, subchronic",
author = "Nielsen, {Brian S.} and Larsen, {Erik Huusfeldt} and Ole Ladefoged and Lam, {Henrik Rye}",
year = "2017",
doi = "10.1177/1091581817704378",
language = "English",
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journal = "International Journal of Toxicology",
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Subchronic, Low-Level Intraperitoneal Injections of Manganese (IV) Oxide and Manganese (II) Chloride Affect Rat Brain Neurochemistry. / Nielsen, Brian S.; Larsen, Erik Huusfeldt; Ladefoged, Ole; Lam, Henrik Rye.

In: International Journal of Toxicology, Vol. 36, No. 3, 2017, p. 239-251.

Research output: Contribution to journalJournal articleResearchpeer-review

TY - JOUR

T1 - Subchronic, Low-Level Intraperitoneal Injections of Manganese (IV) Oxide and Manganese (II) Chloride Affect Rat Brain Neurochemistry

AU - Nielsen, Brian S.

AU - Larsen, Erik Huusfeldt

AU - Ladefoged, Ole

AU - Lam, Henrik Rye

PY - 2017

Y1 - 2017

N2 - Manganese (Mn) is neurotoxic and can induce manganism, a Parkinson-like disease categorized as being a serious central nervous system irreversible neurodegenerative disease. An increased risk of developing symptoms of Parkinson disease has been linked to work-related exposure, for example, for workers in agriculture, horticulture, and people living near areas with frequent use of Mn-containing pesticides. In this study, the focus was placed on neurochemical effects of Mn. Rats were dosed intraperitoneally with 0.9% NaCl (control), 1.22 mg Mn (as MnO2)/kg bodyweight (bw)/day, or 2.5 mg Mn (as MnCl2)/kg bw/day for 7 d/wk for 8 or 12 weeks. This dosing regimen adds relevant new knowledge about Mn neurotoxicity as a consequence of low-dose subchronic Mn dosing. Manganese concentrations increased in the striatum, the rest of the brain, and in plasma, and regional brain neurotransmitter concentrations, including noradrenaline, dopamine (DA), 5-hydroxytrytamine, glutamate, taurine, and γ-amino butyric acid, and the activity of acetylcholinesterase changed. Importantly, a target parameter for Parkinson disease and manganism, the striatal DA concentration, was reduced after 12 weeks of dosing with MnCl2. Plasma prolactin concentration was not significantly affected due to a potentially reduced dopaminergic inhibition of the prolactin release from the anterior hypophysis. No effects on the striatal α-synuclein and synaptophysin protein levels were detected.

AB - Manganese (Mn) is neurotoxic and can induce manganism, a Parkinson-like disease categorized as being a serious central nervous system irreversible neurodegenerative disease. An increased risk of developing symptoms of Parkinson disease has been linked to work-related exposure, for example, for workers in agriculture, horticulture, and people living near areas with frequent use of Mn-containing pesticides. In this study, the focus was placed on neurochemical effects of Mn. Rats were dosed intraperitoneally with 0.9% NaCl (control), 1.22 mg Mn (as MnO2)/kg bodyweight (bw)/day, or 2.5 mg Mn (as MnCl2)/kg bw/day for 7 d/wk for 8 or 12 weeks. This dosing regimen adds relevant new knowledge about Mn neurotoxicity as a consequence of low-dose subchronic Mn dosing. Manganese concentrations increased in the striatum, the rest of the brain, and in plasma, and regional brain neurotransmitter concentrations, including noradrenaline, dopamine (DA), 5-hydroxytrytamine, glutamate, taurine, and γ-amino butyric acid, and the activity of acetylcholinesterase changed. Importantly, a target parameter for Parkinson disease and manganism, the striatal DA concentration, was reduced after 12 weeks of dosing with MnCl2. Plasma prolactin concentration was not significantly affected due to a potentially reduced dopaminergic inhibition of the prolactin release from the anterior hypophysis. No effects on the striatal α-synuclein and synaptophysin protein levels were detected.

KW - Parkinson’s disease

KW - manganese

KW - manganese speciation

KW - manganism

KW - neurotoxicity

KW - subchronic

U2 - 10.1177/1091581817704378

DO - 10.1177/1091581817704378

M3 - Journal article

VL - 36

SP - 239

EP - 251

JO - International Journal of Toxicology

JF - International Journal of Toxicology

SN - 1091-5818

IS - 3

ER -