Increase in hippocampal cell death after treatment with kainate in zinc deficiency.
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.
Takeda
Atsushi
A
Department of Medical Biochemistry, School of Pharmaceutical Sciences, University of Shizuoka, 52-1 Yada, Shizuoka 422-8526, Japan. takedaa@u-shizuoka-ken.ac.jp
Tamano
Haruna
H
Nagayoshi
Akito
A
Yamada
Kohei
K
Oku
Naoto
N
D000818:Animals; D016923:Cell Death / Q000187:drug effects / Q000502:physiology; D004195:Disease Models, Animal; D004198:Disease Susceptibility / Q000378:metabolism / Q000503:physiopathology; D004827:Epilepsy / Q000139:chemically induced / Q000378:metabolism* / Q000503:physiopathology; D018690:Excitatory Amino Acid Agonists / Q000633:toxicity; D045604:Extracellular Fluid / Q000378:metabolism; D005526:Food, Formulated; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism* / Q000503:physiopathology; D020287:In Situ Nick-End Labeling; D007274:Injections, Intraperitoneal; D007608:Kainic Acid / Q000633:toxicity*; D008297:Male; D051379:Mice; D009410:Nerve Degeneration / Q000139:chemically induced / Q000378:metabolism* / Q000503:physiopathology; D009498:Neurotoxins / Q000633:toxicity; D017966:Pyramidal Cells / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D015854:Up-Regulation / Q000187:drug effects / Q000502:physiology; D015032:Zinc / Q000172:deficiency*
D018690:Excitatory Amino Acid Agonists; D009498:Neurotoxins; D015032:Zinc; D007608:Kainic Acid