Impaired cognitive performance in ornithine transcarbamylase-deficient mice on arginine-free diet

Abstract

Sparse-fur ( spf) mice are a model for the congenital deficiency of ornithine transcarbamylase (OTC), the most common inborn error of urea synthesis in man. In this study, performance of clinically stable spf and control mice (8–10-weeks-old) on two learning tests was assessed under normal Arg(+) or arginine-free Arg(−) diet conditions. Used as an indicator of the metabolic status of the animals, plasma ammonia concentrations were significantly higher in spf than in controls on normal diet, and increased even more during the Arg(−) diet episode. Behaviourally, we found no difference in passive avoidance learning between control and spf mice on Arg(+) diet, whereas in spf mice receiving Arg(−) diet during training, retention performance was significantly reduced. In the hidden-platform water maze, spf mice on Arg(+) diet only showed decreased swimming velocity compared to controls. In mice on Arg(−) diet during the first week of acquisition training, performance on acquisition and retention (probe) trials showed that spf mice experienced more difficulties in actually locating the platform. Visible-platform control experiments only showed a reduction in swimming velocity in spf mice on either diet. We conclude that cognitive performance is impaired in spf mice as a consequence of Arg(−) diet-induced neurochemical alterations.