TY - JOUR
T1 - Alterations of oxidative stress biomarkers due to in utero and neonatal exposures of airborne manganese
AU - Erikson, Keith M.
AU - Dorman, David C.
AU - Fitsanakis, Vanessa
AU - Lash, Lawrence H.
AU - Aschner, Michael
N1 - Funding Information:
This article is based on a study sponsored and funded by Afton Chemical Corporation in satisfaction of registration requirements arising under Section 211(a) and (b) of the Clean Air Act and corresponding regulations at 40 C.F.R. Subsections 79.50 et seq.
PY - 2006
Y1 - 2006
N2 - Neonatal rats were exposed to airborne manganese sulfate (MnSO4) (0, 0.05, 0.5, or 1.0 mg Mn/m3) during gestation (d 0-19) and postnatal days (PNDs) 1-18. On PND 19, 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) and tyrosine hydroxylase (TH) protein levels, metallothionein (MT), TH and GS mRNA levels, and reduced and oxidized glutathione (GSH and GSSG, respectively) levels were determined for all five regions. Mn exposure (all three doses) significantly (p ≤ 0.0021) decreased GS protein levels in the cerebellum, and GS mRNA levels were significantly (p ≤ 0.0008) decreased in the striatum. Both the median and high dose of Mn significantly (p ≤ 0.0114) decreased MT mRNA in the striatum. Mn exposure had no effect on TH protein levels, but it significantly lowered TH mRNA levels in the olfactory bulb (p ≤ 0.0402) and in the striatum (p ≤ 0.0493). Mn exposure significantly lowered GSH levels at the median dose in the olfactory bulb (p ≤ 0.0032) and at the median and high dose in the striatum (p ≤ 0.0346). Significantly elevated (p ≤ 0.0247) GSSG, which can be indicative of oxidative stress, was observed in the cerebellum of pups exposed to the high dose of Mn. These data reveal that alterations of oxidative stress biomarkers resulting from in utero and neonatal exposures of airborne Mn exist. Coupled with our previous study in which similarly exposed rats were allowed to recover from Mn exposure for 3 wk, it appears that many of these changes are reversible. It is important to note that the doses of Mn utilized represent levels that are a hundred- to a thousand-fold higher than the inhalation reference concentration set by the United States Environmental Protection Agency.
AB - Neonatal rats were exposed to airborne manganese sulfate (MnSO4) (0, 0.05, 0.5, or 1.0 mg Mn/m3) during gestation (d 0-19) and postnatal days (PNDs) 1-18. On PND 19, 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) and tyrosine hydroxylase (TH) protein levels, metallothionein (MT), TH and GS mRNA levels, and reduced and oxidized glutathione (GSH and GSSG, respectively) levels were determined for all five regions. Mn exposure (all three doses) significantly (p ≤ 0.0021) decreased GS protein levels in the cerebellum, and GS mRNA levels were significantly (p ≤ 0.0008) decreased in the striatum. Both the median and high dose of Mn significantly (p ≤ 0.0114) decreased MT mRNA in the striatum. Mn exposure had no effect on TH protein levels, but it significantly lowered TH mRNA levels in the olfactory bulb (p ≤ 0.0402) and in the striatum (p ≤ 0.0493). Mn exposure significantly lowered GSH levels at the median dose in the olfactory bulb (p ≤ 0.0032) and at the median and high dose in the striatum (p ≤ 0.0346). Significantly elevated (p ≤ 0.0247) GSSG, which can be indicative of oxidative stress, was observed in the cerebellum of pups exposed to the high dose of Mn. These data reveal that alterations of oxidative stress biomarkers resulting from in utero and neonatal exposures of airborne Mn exist. Coupled with our previous study in which similarly exposed rats were allowed to recover from Mn exposure for 3 wk, it appears that many of these changes are reversible. It is important to note that the doses of Mn utilized represent levels that are a hundred- to a thousand-fold higher than the inhalation reference concentration set by the United States Environmental Protection Agency.
KW - Brain
KW - Glutamine synthetase
KW - Glutathione
KW - In utero
KW - Manganese
KW - Metallothionein
KW - Rat
KW - Tyrosine hydroxylase
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U2 - 10.1385/BTER:111:1:199
DO - 10.1385/BTER:111:1:199
M3 - Article
C2 - 16943606
AN - SCOPUS:33748603757
SN - 0163-4984
VL - 111
SP - 199
EP - 215
JO - Biological Trace Element Research
JF - Biological Trace Element Research
IS - 1-3
ER -