title: Aging, motor function, and sensitivity to calcium channel blockers: An investigation using chronic methylmercury exposure.
abstract: Methylmercury (MeHg) neurotoxicity is thought to be mediated, in part, by dysregulation of calcium (Ca(2+)) homeostasis, a mechanism that may also slowly and progressively degrade neuronal function during normal aging. Longitudinal studies of MeHg exposure provide a powerful approach to studying neural and behavioral mechanisms by which both MeHg toxicity and aging affect motor function. Wheel-running and rotarod performance were assessed in two age groups of BALB/c mice chronically exposed to 0 or 1.2mg/kg/day MeHg and 0 or 20mg/kg/day nimodipine, a 1,4-dihyrdopyridine L-type calcium channel blocker (CCB), for approximately 8.5 months. Adults began exposure on postnatal day (PND) 72 and retired breeders on PND 296. A log-survivor bout analysis partitioned wheel-running into bouts that identified motor (within-bout rates) and motivational (bout-initiation rates) influences. Retired breeders ran farther, because of a higher bout-initiation rates, but performed more poorly on the rotarod than younger adults, a difference unaffected by nimodipine. MeHg produced relatively age-independent deficits in wheel-running and rotarod performance, whereas nimodipine afforded greater protection to adult mice than to retired breeders. Rotarod performance and within-bout response rate were more sensitive to and more reliable predictors of MeHg toxicity than bout-initiation rate, which was least affected by MeHg exposure. Thus the motivation to run was unimpaired as the ability to do so declined. While chronic MeHg exposure produced functionally similar behavior deficits between age groups, the age-dependent neuroprotection by nimodipine supports the notion that underlying neurobiological systems mediated by Ca(2+) signaling, are differentially affected in older adults.
authors.affiliation: Sanders-Brown Center on Aging, University of Kentucky, United States.
authors.forename: Andrew Nathanael
authors.initials: AN
authors.lastname: Shen
authors.affiliation: Department of Psychology, University of Alabama, United States.
authors.forename: Craig
authors.initials: C
authors.lastname: Cummings
authors.affiliation: Department of Psychology, Indiana University Southeast, United States.
authors.forename: Daniel
authors.initials: D
authors.lastname: Hoffman
authors.affiliation: Virginia Tech Carilion Research Institute's Addiction Recovery Research Center, United States.
authors.forename: Derek
authors.initials: D
authors.lastname: Pope
authors.affiliation: Department of Psychology, Behavioral Toxicology Lab, Auburn University, United States.
authors.forename: Megan
authors.initials: M
authors.lastname: Arnold
authors.affiliation: Department of Psychology, Behavioral Toxicology Lab, Auburn University, United States. Electronic address: newlamc@auburn.edu.
authors.forename: M Christopher
authors.initials: MC
authors.lastname: Newland
mesh_terms: D000375:Aging; D000818:Animals; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D008297:Male; D008630:Mercury Poisoning / Q000188:drug therapy* / Q000209:etiology; D008767:Methylmercury Compounds / Q000633:toxicity*; D051379:Mice; D008807:Mice, Inbred BALB C; D009042:Motivation / Q000187:drug effects; D009043:Motor Activity / Q000187:drug effects*; D009553:Nimodipine / Q000494:pharmacology*; D045442:Rotarod Performance Test; D013997:Time Factors
chemical_list: D002121:Calcium Channel Blockers; D008767:Methylmercury Compounds; D009553:Nimodipine
keywords: Aging; Bout analysis; Calcium; Methylmercury; Nimodipine; Rotarod; Wheel-running