Supplementation with L-histidine during dietary zinc repletion improves short-term memory in zinc-restricted young adult male rats

Zinc, an essential dietary element, modulates neurotransmission in brain re gions associated with cognition. Cognitive dysfunction has been reported in offspring of female rats fed zinc-restricted diets during gestation and/or lactation, Studies on the cognitive effects of zinc restriction during you ng adulthood are limited. After a 3-wk period of dietary zinc restriction, male rats (71-75 d old) were repleted with zinc chloride alone, or zinc chl oride supplemented with L-histidine, and short-term memory was measured usi ng the Morris water maze. During restriction, zinc-restricted rats demonstr ated significantly longer (86.0%) retrieval latencies than nonrestricted co ntrols, and significantly lower liver (25.5%), bone (32.5%) and hippocampal (3.2%) zinc concentrations. During subsequent repletion, rats repleted wit h zinc chloride supplemented with L-histidine improved their retrieval late ncies to the extent that they were no longer significantly different from c ontrols by repletion d 3. This was associated with a return of hippocampal zinc concentrations to control values by repletion d 3. The mean retrieval escape latencies of the zinc chloride-repleted rats remained significantly prolonged (75.0%). Collectively, these data indicate the following: 1) feed ing a zinc-restricted diet for 3 wk impairs short-term memory in young adul t male rats, and 2) repletion with dietary zinc supplemented with L-histidi ne improves short-term memory function more efficiently than dietary zinc c hloride alone. The latter point suggests that dietary zinc supplemented wit h L-histidine is more bioavailable to the brain than zinc provided as zinc chloride alone. These findings are important in that they highlight the imp ortance of both dietary zinc formulation and the use of functional assessme nts in determining zinc nutriture.