Airborne manganese exposure differentially affects end points of oxidative stress in an age- and sex-dependent manner

Keith M. Erikson, David C. Dorman, Lawrence H. Lash, Allison W. Dobson, Michael Aschner

Research output: Contribution to journalArticle

25 Citations (Scopus)

Abstract

Juvenile female and male (young) and 16-mo-old male (old) rats inhaled manganese in the form of manganese sulfate (MnSO4) at 0, 0.01, 0.1, and 0.5 mg Mn/m3 or manganese phosphate at 0.1 mg Mn/m3 in exposures of 6 h/d, 5 d/wk for 13 wk. We assessed biochemical end points indicative of oxidative stress in five brain regions: cerebellum, hippocampus, hypothalamus, olfactory bulb, and striatum. Glutamine synthetase (GS) protein levels, metallothionein (MT) and GS mRNA levels, and total glutathione (GSH) levels were determined for all five regions. Although most brain regions in the three groups of animals were unaffected by manganese exposure in terms of GS protein levels, there was significantly increased protein (p<0.05) in the hippocampus and decreased protein in the hypothalamus of young male rats exposed to manganese phosphate as well as in the aged rats exposed to 0.1 mg/m 3 MnSO4. Conversely, GS protein was elevated in the olfactory bulb of females exposed to the high dose of MnSO4. Statistically significant decreases (p<0.05) in MT and GS mRNA as a result of manganese exposure were observed in the cerebellum, olfactory bulb, and hippocampus in the young male rats, in the hypothalamus in the young female rats, and in the hippocampus in the senescent males. Total GSH levels significantly (p<0.05) decreased in the olfactory bulb of manganese exposed young male rats and increased in the olfactory bulb of female rats exposed to manganese. Both the aged and young female rats had significantly decreased (p<0.05) GSH in the striatum resulting from manganese inhalation. The old male rats also had depleted GSH levels in the cerebellum and hypothalamus as a result of the 0.1-mg/m3 manganese phosphate exposure. These results demonstrate that age and sex are variables that must be considered when assessing the neurotoxicity of manganese.

Original languageEnglish (US)
Pages (from-to)49-62
Number of pages14
JournalBiological Trace Element Research
Volume100
Issue number1
StatePublished - Jul 2004
Externally publishedYes

Fingerprint

Oxidative stress
Manganese
Rats
Oxidative Stress
Glutamate-Ammonia Ligase
Olfactory Bulb
Hypothalamus
Hippocampus
Cerebellum
Metallothionein
Proteins
Brain
Messenger RNA
Inhalation
Glutathione
Animals

Keywords

  • Brain
  • Glutamine synthetase
  • Glutathione
  • Manganese
  • Metallothionein
  • Oxidative stress
  • Rat

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Endocrinology
  • Endocrinology, Diabetes and Metabolism

Cite this

Airborne manganese exposure differentially affects end points of oxidative stress in an age- and sex-dependent manner. / Erikson, Keith M.; Dorman, David C.; Lash, Lawrence H.; Dobson, Allison W.; Aschner, Michael.

In: Biological Trace Element Research, Vol. 100, No. 1, 07.2004, p. 49-62.

Research output: Contribution to journalArticle

Erikson, Keith M. ; Dorman, David C. ; Lash, Lawrence H. ; Dobson, Allison W. ; Aschner, Michael. / Airborne manganese exposure differentially affects end points of oxidative stress in an age- and sex-dependent manner. In: Biological Trace Element Research. 2004 ; Vol. 100, No. 1. pp. 49-62.
@article{146ba46562b24447a9501df5e2096421,
title = "Airborne manganese exposure differentially affects end points of oxidative stress in an age- and sex-dependent manner",
abstract = "Juvenile female and male (young) and 16-mo-old male (old) rats inhaled manganese in the form of manganese sulfate (MnSO4) at 0, 0.01, 0.1, and 0.5 mg Mn/m3 or manganese phosphate at 0.1 mg Mn/m3 in exposures of 6 h/d, 5 d/wk for 13 wk. We assessed biochemical end points indicative of oxidative stress in five brain regions: cerebellum, hippocampus, hypothalamus, olfactory bulb, and striatum. Glutamine synthetase (GS) protein levels, metallothionein (MT) and GS mRNA levels, and total glutathione (GSH) levels were determined for all five regions. Although most brain regions in the three groups of animals were unaffected by manganese exposure in terms of GS protein levels, there was significantly increased protein (p<0.05) in the hippocampus and decreased protein in the hypothalamus of young male rats exposed to manganese phosphate as well as in the aged rats exposed to 0.1 mg/m 3 MnSO4. Conversely, GS protein was elevated in the olfactory bulb of females exposed to the high dose of MnSO4. Statistically significant decreases (p<0.05) in MT and GS mRNA as a result of manganese exposure were observed in the cerebellum, olfactory bulb, and hippocampus in the young male rats, in the hypothalamus in the young female rats, and in the hippocampus in the senescent males. Total GSH levels significantly (p<0.05) decreased in the olfactory bulb of manganese exposed young male rats and increased in the olfactory bulb of female rats exposed to manganese. Both the aged and young female rats had significantly decreased (p<0.05) GSH in the striatum resulting from manganese inhalation. The old male rats also had depleted GSH levels in the cerebellum and hypothalamus as a result of the 0.1-mg/m3 manganese phosphate exposure. These results demonstrate that age and sex are variables that must be considered when assessing the neurotoxicity of manganese.",
keywords = "Brain, Glutamine synthetase, Glutathione, Manganese, Metallothionein, Oxidative stress, Rat",
author = "Erikson, {Keith M.} and Dorman, {David C.} and Lash, {Lawrence H.} and Dobson, {Allison W.} and Michael Aschner",
year = "2004",
month = "7",
language = "English (US)",
volume = "100",
pages = "49--62",
journal = "Biological Trace Element Research",
issn = "0163-4984",
publisher = "Humana Press",
number = "1",

}

TY - JOUR

T1 - Airborne manganese exposure differentially affects end points of oxidative stress in an age- and sex-dependent manner

AU - Erikson, Keith M.

AU - Dorman, David C.

AU - Lash, Lawrence H.

AU - Dobson, Allison W.

AU - Aschner, Michael

PY - 2004/7

Y1 - 2004/7

N2 - Juvenile female and male (young) and 16-mo-old male (old) rats inhaled manganese in the form of manganese sulfate (MnSO4) at 0, 0.01, 0.1, and 0.5 mg Mn/m3 or manganese phosphate at 0.1 mg Mn/m3 in exposures of 6 h/d, 5 d/wk for 13 wk. We assessed biochemical end points indicative of oxidative stress in five brain regions: cerebellum, hippocampus, hypothalamus, olfactory bulb, and striatum. Glutamine synthetase (GS) protein levels, metallothionein (MT) and GS mRNA levels, and total glutathione (GSH) levels were determined for all five regions. Although most brain regions in the three groups of animals were unaffected by manganese exposure in terms of GS protein levels, there was significantly increased protein (p<0.05) in the hippocampus and decreased protein in the hypothalamus of young male rats exposed to manganese phosphate as well as in the aged rats exposed to 0.1 mg/m 3 MnSO4. Conversely, GS protein was elevated in the olfactory bulb of females exposed to the high dose of MnSO4. Statistically significant decreases (p<0.05) in MT and GS mRNA as a result of manganese exposure were observed in the cerebellum, olfactory bulb, and hippocampus in the young male rats, in the hypothalamus in the young female rats, and in the hippocampus in the senescent males. Total GSH levels significantly (p<0.05) decreased in the olfactory bulb of manganese exposed young male rats and increased in the olfactory bulb of female rats exposed to manganese. Both the aged and young female rats had significantly decreased (p<0.05) GSH in the striatum resulting from manganese inhalation. The old male rats also had depleted GSH levels in the cerebellum and hypothalamus as a result of the 0.1-mg/m3 manganese phosphate exposure. These results demonstrate that age and sex are variables that must be considered when assessing the neurotoxicity of manganese.

AB - Juvenile female and male (young) and 16-mo-old male (old) rats inhaled manganese in the form of manganese sulfate (MnSO4) at 0, 0.01, 0.1, and 0.5 mg Mn/m3 or manganese phosphate at 0.1 mg Mn/m3 in exposures of 6 h/d, 5 d/wk for 13 wk. We assessed biochemical end points indicative of oxidative stress in five brain regions: cerebellum, hippocampus, hypothalamus, olfactory bulb, and striatum. Glutamine synthetase (GS) protein levels, metallothionein (MT) and GS mRNA levels, and total glutathione (GSH) levels were determined for all five regions. Although most brain regions in the three groups of animals were unaffected by manganese exposure in terms of GS protein levels, there was significantly increased protein (p<0.05) in the hippocampus and decreased protein in the hypothalamus of young male rats exposed to manganese phosphate as well as in the aged rats exposed to 0.1 mg/m 3 MnSO4. Conversely, GS protein was elevated in the olfactory bulb of females exposed to the high dose of MnSO4. Statistically significant decreases (p<0.05) in MT and GS mRNA as a result of manganese exposure were observed in the cerebellum, olfactory bulb, and hippocampus in the young male rats, in the hypothalamus in the young female rats, and in the hippocampus in the senescent males. Total GSH levels significantly (p<0.05) decreased in the olfactory bulb of manganese exposed young male rats and increased in the olfactory bulb of female rats exposed to manganese. Both the aged and young female rats had significantly decreased (p<0.05) GSH in the striatum resulting from manganese inhalation. The old male rats also had depleted GSH levels in the cerebellum and hypothalamus as a result of the 0.1-mg/m3 manganese phosphate exposure. These results demonstrate that age and sex are variables that must be considered when assessing the neurotoxicity of manganese.

KW - Brain

KW - Glutamine synthetase

KW - Glutathione

KW - Manganese

KW - Metallothionein

KW - Oxidative stress

KW - Rat

UR - http://www.scopus.com/inward/record.url?scp=4043074117&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=4043074117&partnerID=8YFLogxK

M3 - Article

C2 - 15258319

AN - SCOPUS:4043074117

VL - 100

SP - 49

EP - 62

JO - Biological Trace Element Research

JF - Biological Trace Element Research

SN - 0163-4984

IS - 1

ER -