Oxidative stress is induced in the rat brain following repeated inhalation exposure to manganese sulfate

Eight-week-old rats inhaled manganese (Mn) in the form of MnSO4 at 0, 0.03, 0.3, or 3.0 mg Mn/m(3) for 6 h/d for 7 d/wk (14 consecutive exposures). Brain manganese concentrations in these animals were reported by Dorman et al. in 2001, noting the following rank order: olfactory bulb > striatum > cerebellum. We assessed biochemical end points indicative of oxidative stress in these three brain regions, as well as the hypothalamus and hippocampus. Glutamine synthetase (GS) protein levels and total glutathione (GSH) levels were determined for all five regions. GS mRNA and metallothionein (MT) mRNA levels were also evaluated for the cerebellum, hypothalamus, and hippocampus. Statistically significant increases (p<0.05) in GS protein were observed in the olfactory bulb upon exposure to the medium and high manganese doses. In the hypothalamus, statistically significant (p<0.05) but more modest increases were also noted in the medium and high manganese dose. Total GSH levels significantly (p<0.05) decreased only in the hypothalamus (high manganese dose), and MT mRNA significantly increased in the hypothalamus (medium manganese dose). No significant changes were noted in any of the measured parameters in the striatum, although manganese concentrations in this region were also increased. These results demonstrate that the olfactory bulb and hypothalamus represent potentially sensitive areas to oxidative stress induced by exceedingly high levels of inhaled manganese sulfate and that other regions, and especially the striatum, are resistant to manganese-induced oxidative stress despite significant accumulation of this metal.