Susceptibility to kainate‐induced seizures under dietary zinc deficiency

Abstract

Zinc homeostasis in the brain is altered by dietary zinc deficiency, and its alteration may be associated with the etiology and manifestation of epileptic seizures. In the present study, susceptibility to kainate-induced seizures was enhanced in mice fed a zinc-deficient diet for 4 weeks. When Timm's stain was performed to estimate zinc concentrations in synaptic vesicles, Timm's stain in the brain was attenuated in the zincdeficient mice. In rats fed the zinc-deficient diet for 4 weeks, susceptibility to kainate-induced seizures was also enhanced. When the release of zinc and neurotransmitters in the hippocampal extracellular fluid of the zinc-deficient rats was studied using in vivo microdialysis, the zinc concentration in the perfusate was less than 50% of that of the control rats and the increased levels of zinc by treatment with kainate were lower than the basal level in control rats, suggesting that vesicular zinc is responsive to dietary zinc deficiency. The levels of glutamate in the perfusate of the zinc-deficient rats were more increased than in the control rats, whereas the levels of GABA in the perfusate were not at all increased in the zincdeficient rats, unlike in the control rats. The present results demonstrate an enhanced release of glutamate associated with a decrease in GABA concentrations as a possible mechanism for the increased seizure susceptibility under zinc deficiency.

Protective Effect of Zinc Against Ischemic Neuronal Injury in a Middle Cerebral Artery Occlusion Model

“…The results that the ZnEDTA-treated group exhibited no significant difference to the saline-treated group also supports this hypothesis. Furthermore, it has been reported that zinc transporter-3 (zincT-3)-null mice, which lack histochemically reactive zinc in synaptic vesicles, or zincdeficient mice are more sensitive to seizures induced with kainate (27,28). These reports also imply that vesicular zinc may exert an inhibitive effect on hyperexcitation.…”

Nutrient-gene interactions: a single nutrient and hundreds of target genes

“…A decreased T-cell number and altered responses of T-lymphocytes to phytomitogens are indicators of a zinc deficiency in the immune system (Allen et al, 1983;Beck et al, 1997;Bao et al, 2003). Endogenous zinc appears to modulate GABA-mediated synaptic transmission and can block Ca qq channels at Unauthenticated Download Date | 5/9/18 8:28 PM the presynaptic level, causing inhibition of neurotransmitter release (Winegar and Lansman, 1990;Harrison and Gibbons, 1994;Takeda et al, 2003).…”

Neo-Timm staining in the thalamus of chronically epileptic rats

“…Depending on the animal model, the receptor type and subunit configuration, zinc can act as a pro-or anticonvulsant agent (32)(33)(34)(35). In animal models of temporal lobe epilepsy, however, zinc seems to decrease seizure activity (34)(35)(36). …”

“…Mice lacking vesicular zinc and dietary zincdeficient rats are not only more susceptible to kainic acid-induced seizures, but also have a higher degree of neuronal injury in the hippocampus (34,35). Whether the neuroprotective effects of zinc derive from a reduced release of glutamate or an increase in the concentration of GABA remains elusive, since both mechanisms have been demonstrated in microdialysis studies (37)(38)(39).…”