Abnormal Ca²⁺ mobilization in hippocampal slices of epileptic animals fed a zinc-deficient diet

Summary 

On the basis of the evidence of the enhanced susceptibility to kainate-induced seizures in zinc-deficient mice and rats, the mechanism of the enhanced susceptibility was examined focused on neuronal Ca²⁺ mobilization. Brain slices were prepared from rats fed a zinc-deficient diet for 4 weeks. Intracellular fura-2 signals in the hippocampal CA3, in which the basal fura-2 signals were higher in zinc deficiency, were significantly more increased 4s after delivery of kainate (1mM/1μl, 1s) to the dentate granule cell layer. Calcium orange signal in mossy fiber boutons was also significantly more increased in zinc deficiency after delivery of tetanic stimuli (100Hz, 5s) to the dentate granule cell layer in the presence of CNQX, a blocker of AMPA/kainate receptors. The decrease in FM4-64 signal, a direct measure of vesicular exocytosis, in mossy fiber boutons during tetanic stimulation (10Hz, 180s) was significantly enhanced in zinc deficiency. These results indicate that intracellular Ca²⁺ mobilization in the hippocampus is affected in zinc deficiency, followed by the enhancement of exocytosis at mossy fiber boutons. In NMDA-challenged mice, which were fed the zinc-deficient diet for 4 weeks, furthermore, seizure susceptibility was significantly enhanced. It is likely that abnormal Ca²⁺ mobilization in neurons is involved in seizure susceptibility in zinc-deficient animals.

Keywords: Zinc deficiency, Epilepsy, NMDA receptor, Calcium mobilization, Hippocampus