Responsiveness to kainate in young rats after 2-week zinc deprivation

Abstract

On the basis of the evidence of the enhanced susceptibility to kainate-induced seizures in young rats fed a zinc-deficient diet for 4 weeks, the relationship between zinc release from hippocampal neuron terminals and seizure susceptibility was studied in young rats fed the zinc-deficient diet for 2 weeks. Timm's stain, with which histochemically reactive zinc in the presynaptic vesicle is detected, was not attenuated in mossy fibers and other areas in the hippocampus after 2-week zinc deprivation, whereas the attenuation was observed after 4-week zinc deprivation. Extracellular zinc concentration was not also decreased after 2-week zinc deprivation, unlike the case after 4-week zinc deprivation. To check the capacity for zinc release from neuron terminals after 2-week zinc deprivation, the hippocampus was excessively stimulated with 100 mM KCl. The increase in extracellular zinc concentration of zinc-deficient group was significantly more than that of control group. These results suggest that zinc release from hippocampal neuron terminals is not affected by 2-week zinc deprivation. On the other hand, the latency in myoclonic jerks of zinc-deficient group was significantly shorter than in the control group after treatment with kainate, while the latency in clonic convulsions was not different between the two groups. Intracellular fura-2 signal, a calcium indicator, was significantly higher in the hippocampal CA3 areas of zinc-deficient group 4 s after delivery of kainate to dentate granule cells. These results suggest that susceptibility to kainate-induced seizures is altered prior to the decrease in extracellular zinc concentration and zinc release from neuron terminals in zinc-deficient young rats. The alteration of calcium signaling seems to be involved in the susceptibility in zinc deficiency.

Zinc Signaling in the Hippocampus and Its Relation to Pathogenesis of Depression

“…The increase in depression-like behavior is reported in zinc-deficient mice [111] and rats [112], and is observed in no appreciable decrease in zinc concentration in the brain [113]. Neuropsychological symptoms are caused prior to the decreases in histochemically reactive zinc and/or extracellular zinc in the brain, which are responsive to zinc deficiency [109,110,114,115]. Thus, abnormal corticosterone secretion induced by dietary zinc deficiency may be critical for neuropsychological symptoms such as depression (Fig.…”

“…Histochemically reactive zinc levels are also lower in aged animals than in adult animals [119,120]. Judging from the evidence that subclinical zinc deficiency is common in old age, it is possible that histochemically reactive zinc levels are reduced with normal aging in humans [16], as well as chronic dietary zinc deficiency in experimental animals [87,114,115] (Fig. 4).…”

High K+-induced Increase in Extracellular Glutamate in Zinc Deficiency and Endogenous Zinc Action

“…21,25) Susceptibility to kainateinduced seizures is altered in young rats after 2-week zinc deprivation. 22) It is possible that the affected Ca 2+ homeostasis influences neuronal activity and seizure susceptibility. On the other hand, Rats were fed a control or zinc-deficient diet.…”

“…The increase in corticosterone secretion is observed prior to the decrease in extracellular zinc concentration in the brain in zinc deficiency. 21,22) In contrast, serum zinc concentration of zinc-deficient rats is less than 50% of that of the control. 21) It is possible that the decrease in serum zinc concentration is linked to the change in corticosterone secretion in zinc deficiency.…”

“…22) To understand the physiological significance of endogenous zinc release under excess excitation in the hippocampus, in the present study, high K + -induced increase in extracellular glutamate and endogenous zinc action against its increase were examined in young rats fed a zinc-deficient diet for 2 weeks.…”