Purpose: Extracellular superoxide dismutase(ecSOD) is the only extracellular enzyme that provides protection against oxidative stress(superoxide) and its expression is tissue dependent.Over-expression of ecSOD has been associated with improved cognitive performance of aged mice in the radial arm maze,whereas in young mice it has been associated with deleterious effects, including impaired long-term potentiation. Previous studies have determined that expression of ecSOD is higher in plasma of 129P3 than C57BL/6 mice, strains which carry wild-type or mutant alleles for ecSOD, respectively.To determine the influence of the different alleles on brain function, congenic mice were developed carrying the wild-type(C57) or mutant(129) alleles on a C57BL/6 background.The purpose of this study was to determine the contribution of allele-dependent differential expression of ecSOD to age-related differences in psychomotor and cognitive performance.
Methods: There were four groups of congenic female C57BL/6 mice in this study 10-or17-month-old mice carrying either the 129 or wild type ecSOD gene(N=13-21).Brain function was assessed in these groups using tests of behavioral arousal,anxiety level,motor skills,and cognition.The cognitive tasks included the water maze, a measure of spatial memory, and a discriminated avoidance task. Anxiety level in the mice was measured by their avoidance of the open arms of an elevated plus maze(EPM).
Results: Age-related declines in performance were detected in most motor and cognitive tasks,independent of the ecSOD genotype.There were no allele-specific effects in the young mice;however such an effect was detected on performance in tests of behavioral arousal and anxiety in the old mice. Seventeen-month-old mice expressing the mutant(129) ecSOD spent more time in the center of an open field and in the open arms of the EPM,and their swim speed in the water maze was slower, when compared to age-matched mice carrying the wild-type(C57)allele.
Conclusions: These results suggest that the differential expression of ecSOD in C57BL/6 mice was not associated with differences in the performance of mice on the majority of the psychomotor and cognitive behavioral tasks.However,the data from the tests of behavioral arousal, the elevated plus maze, and swim speed suggest that there is an anxiolytic effect associated with the mutant(129)allele. Thus, the extracellular redox state in the brain may have a significant influence on level of anxiety.