Persistent alterations in biomarkers of oxidative stress resulting from combined in utero and neonatal manganese inhalation

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

Research output: Contribution to journalArticle

20 Citations (Scopus)

Abstract

Neonatal female and male rats were exposed to airborne manganese sulfate (MnSO4) during gestation and postnatal d 1-18. Three weeks post-exposure, rats were killed and 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. Overall, there was a statistically significant effect of manganese exposure on decreasing brain GS protein levels (p=0.0061), although only the highest dose of manganese (1 mg Mn/m3) caused a significant increase in GS messenger RNA (mRNA) in both the hypothalamus and olfactory bulb of male rats and a significant decrease in GS mRNA in the striatum of female rats. This highest dose of manganese had no effect on MT mRNA in either males or females; however, the lowest dose (0.05 mg Mn/m3) decreased MT mRNA in the hippocampus, hypothalamus, and striatum in males. The median dose (0.5 mg Mn/m3) led to decreased MT mRNA in the hippocampus and hypothalamus of the males and olfactory bulb of the females. Overall, manganese exposure did not affect total GSH levels, a finding that is contrary to those in our previous studies. Only the cerebellum of manganese-exposed young male rats showed a significant reduction (p<0.05) in total GSH levels compared to control levels. These data reveal that alterations in biomarkers of oxidative stress resulting from in utero and neonatal exposures of airborne manganese remain despite 3 wk of recovery; however, it is important to note that the doses of manganese utilized represent levels that are 100-fold to a 1000-fold higher than the inhalation reference concentration set by the US Environmental Protection Agency.

Original languageEnglish (US)
Pages (from-to)151-163
Number of pages13
JournalBiological Trace Element Research
Volume104
Issue number2
DOIs
StatePublished - May 2005
Externally publishedYes

Fingerprint

Oxidative stress
Biomarkers
Manganese
Inhalation
Glutamate-Ammonia Ligase
Oxidative Stress
Metallothionein
Rats
Messenger RNA
Hypothalamus
Olfactory Bulb
Hippocampus
Cerebellum
Brain
United States Environmental Protection Agency
Level control
Environmental Protection Agency
Glutathione
Proteins
Recovery

Keywords

  • Brain
  • Glutamine synthetase
  • Glutathione
  • In utero
  • Manganese
  • Metallothionein
  • Rat

ASJC Scopus subject areas

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

Cite this

Persistent alterations in biomarkers of oxidative stress resulting from combined in utero and neonatal manganese inhalation. / Erikson, Keith M.; Dorman, David C.; Lash, Lawrence H.; Aschner, Michael.

In: Biological Trace Element Research, Vol. 104, No. 2, 05.2005, p. 151-163.

Research output: Contribution to journalArticle

@article{801f661463f94b01aaafe462149c1092,
title = "Persistent alterations in biomarkers of oxidative stress resulting from combined in utero and neonatal manganese inhalation",
abstract = "Neonatal female and male rats were exposed to airborne manganese sulfate (MnSO4) during gestation and postnatal d 1-18. Three weeks post-exposure, rats were killed and 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. Overall, there was a statistically significant effect of manganese exposure on decreasing brain GS protein levels (p=0.0061), although only the highest dose of manganese (1 mg Mn/m3) caused a significant increase in GS messenger RNA (mRNA) in both the hypothalamus and olfactory bulb of male rats and a significant decrease in GS mRNA in the striatum of female rats. This highest dose of manganese had no effect on MT mRNA in either males or females; however, the lowest dose (0.05 mg Mn/m3) decreased MT mRNA in the hippocampus, hypothalamus, and striatum in males. The median dose (0.5 mg Mn/m3) led to decreased MT mRNA in the hippocampus and hypothalamus of the males and olfactory bulb of the females. Overall, manganese exposure did not affect total GSH levels, a finding that is contrary to those in our previous studies. Only the cerebellum of manganese-exposed young male rats showed a significant reduction (p<0.05) in total GSH levels compared to control levels. These data reveal that alterations in biomarkers of oxidative stress resulting from in utero and neonatal exposures of airborne manganese remain despite 3 wk of recovery; however, it is important to note that the doses of manganese utilized represent levels that are 100-fold to a 1000-fold higher than the inhalation reference concentration set by the US Environmental Protection Agency.",
keywords = "Brain, Glutamine synthetase, Glutathione, In utero, Manganese, Metallothionein, Rat",
author = "Erikson, {Keith M.} and Dorman, {David C.} and Lash, {Lawrence H.} and Michael Aschner",
year = "2005",
month = "5",
doi = "10.1385/BTER:104:2:151",
language = "English (US)",
volume = "104",
pages = "151--163",
journal = "Biological Trace Element Research",
issn = "0163-4984",
publisher = "Humana Press",
number = "2",

}

TY - JOUR

T1 - Persistent alterations in biomarkers of oxidative stress resulting from combined in utero and neonatal manganese inhalation

AU - Erikson, Keith M.

AU - Dorman, David C.

AU - Lash, Lawrence H.

AU - Aschner, Michael

PY - 2005/5

Y1 - 2005/5

N2 - Neonatal female and male rats were exposed to airborne manganese sulfate (MnSO4) during gestation and postnatal d 1-18. Three weeks post-exposure, rats were killed and 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. Overall, there was a statistically significant effect of manganese exposure on decreasing brain GS protein levels (p=0.0061), although only the highest dose of manganese (1 mg Mn/m3) caused a significant increase in GS messenger RNA (mRNA) in both the hypothalamus and olfactory bulb of male rats and a significant decrease in GS mRNA in the striatum of female rats. This highest dose of manganese had no effect on MT mRNA in either males or females; however, the lowest dose (0.05 mg Mn/m3) decreased MT mRNA in the hippocampus, hypothalamus, and striatum in males. The median dose (0.5 mg Mn/m3) led to decreased MT mRNA in the hippocampus and hypothalamus of the males and olfactory bulb of the females. Overall, manganese exposure did not affect total GSH levels, a finding that is contrary to those in our previous studies. Only the cerebellum of manganese-exposed young male rats showed a significant reduction (p<0.05) in total GSH levels compared to control levels. These data reveal that alterations in biomarkers of oxidative stress resulting from in utero and neonatal exposures of airborne manganese remain despite 3 wk of recovery; however, it is important to note that the doses of manganese utilized represent levels that are 100-fold to a 1000-fold higher than the inhalation reference concentration set by the US Environmental Protection Agency.

AB - Neonatal female and male rats were exposed to airborne manganese sulfate (MnSO4) during gestation and postnatal d 1-18. Three weeks post-exposure, rats were killed and 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. Overall, there was a statistically significant effect of manganese exposure on decreasing brain GS protein levels (p=0.0061), although only the highest dose of manganese (1 mg Mn/m3) caused a significant increase in GS messenger RNA (mRNA) in both the hypothalamus and olfactory bulb of male rats and a significant decrease in GS mRNA in the striatum of female rats. This highest dose of manganese had no effect on MT mRNA in either males or females; however, the lowest dose (0.05 mg Mn/m3) decreased MT mRNA in the hippocampus, hypothalamus, and striatum in males. The median dose (0.5 mg Mn/m3) led to decreased MT mRNA in the hippocampus and hypothalamus of the males and olfactory bulb of the females. Overall, manganese exposure did not affect total GSH levels, a finding that is contrary to those in our previous studies. Only the cerebellum of manganese-exposed young male rats showed a significant reduction (p<0.05) in total GSH levels compared to control levels. These data reveal that alterations in biomarkers of oxidative stress resulting from in utero and neonatal exposures of airborne manganese remain despite 3 wk of recovery; however, it is important to note that the doses of manganese utilized represent levels that are 100-fold to a 1000-fold higher than the inhalation reference concentration set by the US Environmental Protection Agency.

KW - Brain

KW - Glutamine synthetase

KW - Glutathione

KW - In utero

KW - Manganese

KW - Metallothionein

KW - Rat

UR - http://www.scopus.com/inward/record.url?scp=23844485986&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=23844485986&partnerID=8YFLogxK

U2 - 10.1385/BTER:104:2:151

DO - 10.1385/BTER:104:2:151

M3 - Article

C2 - 15894815

AN - SCOPUS:23844485986

VL - 104

SP - 151

EP - 163

JO - Biological Trace Element Research

JF - Biological Trace Element Research

SN - 0163-4984

IS - 2

ER -