Effect of methylmercury (MeHg) on DNA oxidation in the brains of adult male mice.

Abstract

Interest in the cellular and biochemical mechanism of MeHg toxicity has stemmed from observed motor and cognitive impairments caused by this organometallic cation in adult humans and rodents. This lab group has confirmed that chronic oral MeHg exposure causes coordinated motor deficits and increased levels of oxidative stress in brain tissue. In the present study, we investigate specific neuroanatomical areas associated with motor and cognitive behaviors that are damaged by MeHg-induced oxidative stress. Adult male mice received 4.8 μg/g/day MeHg orally for 28 days. In order to assess oxidative stress, 8-hydroxy-2’-deoxyguanosine (8-OHdG) was immunohistochemically labeled and analyzed as a biomarker of MeHg-induced DNA oxidation. As hypothesized, MeHg treatment increased 8-OHdG immunoreactivity in the motor cortex. Interestingly, MeHg treatment caused no change in 8-OHdG immunoreactivity in the CA3 region of the hippocampus (CA3) and decreased 8-OHdG immunoreactivity in the magnocellular red nucleus (RMC) and accessory oculomotor nucleus (MA3). These data indicate that 8-OHdG can be used as a sensitive and reliable measure of region specific MeHg-induced oxidative stress in adults. Further investigation is necessary to confirm areas of MeHg-induced neurodegeneration, determine how MeHg-induced oxidative stress causes this degeneration, and identify how this damage produces motor and cognitive impairments.