Metallothionein I,II deficient mice do not exhibit significantly worse long-term behavioral outcomes following neonatal hypoxia-ischemia: MT-I,II deficient mice have inherent behavioral impairments.
Metallothionein I and II are small metal binding proteins with a high affinity for zinc. They are found in the CNS and are thought to play a role in modulating the effects of free zinc. We hypothesized that MT-I,II deficient mice would have more neurological deficits both functionally and anatomically following a neonatal hypoxic-ischemic (HI) insult than wild-type mice subjected to the same insult. Forty wild-type and 40 MT-I,II deficient C57 X 129T2 F1 P10 mice were randomized to either 45 min of HI or sham HI. Beginning on P50, the mice were given a series of behavioral tests including locomotor activity, novel object recognition, Morris water maze (cued, hidden platform, reduced platform), a 2-week-delayed probe trial and an apomorphine-induced rotation test. At the conclusion of testing, the brains were removed for histological analysis including staining with NeuN and GFAP to assess neuronal loss and reactive gliosis. There were no significant differences in functional or anatomic measures between the wild-type HI mice and the MT-I,II deficient HI mice. The MT-I,II deficient mice exhibited an impaired rate of learning in the spatially oriented mazes but once learned retained the information as well as the wild-type mice. The absence of functional MT-I,II proteins does not result in significantly worse injury following 45 min of HI on P10. The MT-I,II deficient mice have baseline impairments in spatial learning but not retention.
McAuliffe
John J
JJ
Department of Anesthesia, Cincinnati Children's, Hospital Medical Center and The University of Cincinnati, Cincinnati OH 45229, USA. john.mcauliffe@cchmc.org
Joseph
Bernadin
B
Hughes
Elizabeth
E
Miles
Lili
L
Vorhees
Charles V
CV
D000704:Analysis of Variance; D000818:Animals; D000831:Animals, Newborn; D005106:Exploratory Behavior / Q000502:physiology; D007839:Functional Laterality / Q000502:physiology; D006624:Hippocampus / Q000201:enzymology* / Q000473:pathology / Q000503:physiopathology; D020925:Hypoxia-Ischemia, Brain / Q000201:enzymology* / Q000473:pathology / Q000503:physiopathology; D007527:Isoenzymes / Q000172:deficiency / Q000235:genetics / Q000378:metabolism; D018782:Maze Learning / Q000502:physiology*; D008668:Metallothionein / Q000172:deficiency* / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008817:Mice, Mutant Strains; D009043:Motor Activity / Q000502:physiology; D009929:Organ Size; D011897:Random Allocation; D012153:Retention, Psychology / Q000502:physiology*; D016037:Single-Blind Method; D015032:Zinc / Q000378:metabolism
D007527:Isoenzymes; C491054:Mt2 protein, mouse; D008668:Metallothionein; D015032:Zinc