A behavioral and biomechanical analysis of the effects of MeHg-induced neurotoxicity on locomotor behaviors and the protective effects of N-Acetylcysteine in adult male mice.

Abstract

Methylmercury (MeHg) is a potent neurotoxin which humans are commonly exposed to through seafood consumption. Developmental exposure to MeHg is known to induce severe neurological deficits in the central nervous system (CNS) resulting in cognitive and locomotor impairments. However, the neurotoxic effects of MeHg in the adult nervous system are not well defined. Additionally, a number of recent studies have suggested damage to endogenous antioxidant functioning resulting in high concentrations of reactive oxygen species (ROS) as a causal factor for oxidative stress as the mechanism by which MeHg damages the CNS. Further exploration of the mechanism by which MeHg induces neurotoxicity in conjunction with an examination of the neurotoxic effects in adult behavior is necessary to provide a concrete understanding of the neurological damages associated with a developed nervous system. The present study observed adult mice administered a daily dose of 4.8 mg/kg MeHg in cookies and injections of a synthetic antioxidant N-Acetylcysteine (NAC) over the course of four weeks. A suite of behavioral tests such as inverted screen, rotor-rod, open field, and analyses of gait patterns, were conducted to measure strength, motor coordination, locomotor activity, and underlying biomechanical physiology following exposure to MeHg. Through the present investigation, quantitative deficits in the locomotor behavior of adult mice were observed through the development and application of sensitive quantitative biomechanical and behavioral measures of locomotor analysis. Furthermore, the exploration of protective effects of NAC on oxidative stress induced by MeHg revealed a positive effect on rate of survival, however, no effect on observed locomotor behaviors in mice exposed to MeHg. Further exploration of the methodologies implemented in the study may provide additional insight into the mechanism of MeHg-induced neurological deficits. This research may advance current understanding of the mechanisms by which MeHg neurological damage occurs in adults and aid in the development of treatment and protective measures.