title: Mercury-induced cognitive impairment in metallothionein-1/2 null mice.
abstract: Metallothioneins are central for the metabolism and detoxification of transition metals. Exposure to mercury during early neurodevelopment is associated with neurocognitive impairment. Given the importance of metallothioneins in mercury detoxification, metallothioneins may be a protective factor against mercury-induced neurocognitive impairment. Deletion of the murine metallothionein-1 and metallothionein-2 genes causes choice accuracy impairments in the 8-arm radial maze. We hypothesize that deletions of metallothioneins genes will make metallothionein-null mice more vulnerable to mercury-induced cognitive impairment. We tested this hypothesis by exposing MT1/MT2-null and wild-type mice to developmental mercury (HgCl(2)) and evaluated the resultant effects on cognitive performance on the 8-arm radial maze. During the early phase of learning metallothionein-null mice were more susceptible to mercury-induced impairment compared to wildtype mice. Neurochemical analysis of the frontal cortex revealed that serotonin levels were higher in metallothionein-null mice compared to wild-type mice. This effect was independent of mercury exposure. However, dopamine levels in mercury-exposed metallothionein-null mice were lower compared to mercury-exposed wild-type mice. This work shows that deleting metallothioneins increase the vulnerability to developmental mercury-induced neurocognitive impairment. Metallothionein effects on monoamine transmitters may be related to this cognitive effect.
authors.affiliation: Department of Psychiatry and Behavioral Sciences, Duke University Medical Center, USA.
authors.forename: Donnie
authors.initials: D
authors.lastname: Eddins
authors.forename: Ann
authors.initials: A
authors.lastname: Petro
authors.forename: Ninitia
authors.initials: N
authors.lastname: Pollard
authors.forename: Jonathan H
authors.initials: JH
authors.lastname: Freedman
authors.forename: Edward D
authors.initials: ED
authors.lastname: Levin
mesh_terms: D000818:Animals; D001923:Brain Chemistry / Q000187:drug effects; D003072:Cognition Disorders / Q000139:chemically induced / Q000235:genetics* / Q000523:psychology*; D005838:Genotype; D018782:Maze Learning / Q000187:drug effects; D020262:Mercury Poisoning, Nervous System / Q000235:genetics* / Q000523:psychology*; D008668:Metallothionein / Q000235:genetics* / Q000502:physiology; D051379:Mice; D018345:Mice, Knockout; D012701:Serotonin / Q000378:metabolism
chemical_list: C491054:Mt2 protein, mouse; C525355:metallothionein-1, mouse; D012701:Serotonin; D008668:Metallothionein