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Increase in hippocampal cell death after treatment with kainate in zinc deficiency.

Takeda A, Tamano H, Nagayoshi A, Yamada K, Oku N

Department of Medical Biochemistry, School of Pharmaceutical Sciences, University of Shizuoka, 52-1 Yada, Shizuoka 422-8526, Japan. takedaa@u-shizuoka-ken.ac.jp

Susceptibility to kainate-induced seizures is enhanced by zinc deficiency. To evaluate kainate-induced excitotoxicity in zinc deficiency, the relationship between kainate-induced seizures and hippocampal cell death was examined in control and zinc-deficient mice. Mice were fed a control and zinc-deficient diet for 4 weeks, and then intraperitoneally injected with 12 mg/kg kainate every 60 min three times. The rate of dead mice to the total mice was higher in zinc-deficient group than in control group 3 days after the last injection of kainate. In the survivals, which exhibited tonic convulsions in both control and zinc-deficient groups, kainate-induced hippocampal cell death was also analyzed by cresyl violet staining. Neuronal loss was more observed in the CA1, CA2 and CA3 pyramidal cell layers of zinc-deficient group than those of the control group. TUNEL-positive cells were significantly more detected in the CA1 and CA3 pyramidal cell layers of zinc-deficient group. These results demonstrate that kainate-induced hippocampal cell death occurs more easily in zinc deficiency. Extracellular zinc concentration detected with ZnAF-2 was significantly decreased in the hippocampal CA3 of zinc-deficient mice, in agreement with the previous data measured by in vivo microdialsysis. Synaptically released zinc may be less involved in kainate-induced hippocampal cell death in zinc deficiency.

Published 17 October 2005 in Neurochem Int, 47(8): 539-44.
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