This Is AuburnElectronic Theses and Dissertations

A bout analysis reveals age-dependent methylmercury neurotoxicity and nimodipine neuroprotection: Implications for the role of calcium homeostasis in aging




Shen, Andrew

Type of Degree





Learning and sensorimotor function decline in normal aging and these deficits may be related to elevations in intracellular calcium (Ca2+) levels [Ca2+]i. The neurotoxicity of methylmercury (MeHg), a ubiquitous environmental contaminant, also appears to be mediated, in part, by elevated [Ca2+]i. Calcium channel blockers (CCBs), which can lower [Ca2+]I, may confer neuroprotection against aging and/or MeHg-induced dysfunction. Studying the effects of chronic MeHg and/or CCB exposure presents a unique way by which to study potential mechanisms of aging. Experiments 1 and 2, conducted simultaneously, chronically exposed two age cohorts (adults and retired breeders) of BALB/c mice to 0 or 10 ppm MeHg and 0 or 200 ppm nimodipine, a CCB, for approximately 8.5 months. Experiment 1 investigated high-rate nose-poking meanwhile Experiment 2 investigated wheel-running and rotarod performance. A bout analysis approach was used to estimate motor and motivational contributions to both nose-poking and wheel-running. Methylmercury produced age-independent mortality and nimodipine afforded protection in an age-dependent manner; there was greater protection in younger animals. Reliably, MeHg-induced motor impairment of nose-poking, wheel-running, and rotarod performance appeared early into exposure while motivational deficits appeared only near mortality. Nimodipine delayed the onset of MeHg-induced behavior deficits and this protection was more pronounced in younger animals. For nose-poking, latency to motor impairment was shorter in older animals than in younger animals. These results provide a comprehensive profile of adult-onset MeHg exposure and also provide support for the use of a bout analysis approach as an analytical tool to delineate between motor and motivational components of behavior.