Ascorbic acid insufficiency impairs spatial memory formation in juvenile AKR1A-knockout mice

AKR1A, an aldo-keto reductase, is involved in the synthesis of ascorbic acid as well as the reduction of a variety of aldehyde compounds. AKR1A−/− mice produce considerably less ascorbic acid (about 10%) compared to AKR1A^+/+ mice and require ascorbic acid supplementation in order to breed. To elucidate the roles played by AKR1A in spatial memory, AKR1A−/− male mice were weaned at 4 weeks of age and groups that received ascorbic acid supple-mentation and no supplementation were subjected to a Morris water maze test. Juvenile AKR1A−/− mice that received no supple-mentation showed impaired spatial memory formation, even though about 70% of the ascorbic acid remained in the brains of the AKR1A−/− mice at day 7 after weaning. To the contrary, the young adult AKR1A−/− mice at 13-15 weeks of age maintained only 15% of ascorbic acid but showed no significant difference in the spatial memory compared with the AKR1A^+/+ mice or ascorbic acid-supplemented AKR1A−/− mice. It is conceivable that juvenile mice require more ascorbic acid for the appropriate level of formation of spatial memory and that maturation of the neural system renders the memory forming process less sensitive to an ascorbic acid insufficiency.