Abnormal Ca2+ mobilization in hippocampal slices of epileptic animals fed a zinc-deficient diet.
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 Ca(2+) 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 (1 mM/1 microl, 1 s) 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 (100 Hz, 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 (10 Hz, 180 s) was significantly enhanced in zinc deficiency. These results indicate that intracellular Ca(2+) 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 Ca(2+) mobilization in neurons is involved in seizure susceptibility in zinc-deficient animals.
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
Itoh
Hiromasa
H
Nagayoshi
Akito
A
Oku
Naoto
N
D000818:Animals; D002118:Calcium / Q000378:metabolism*; D020013:Calcium Signaling / Q000187:drug effects; D004032:Diet; D004558:Electric Stimulation; D004827:Epilepsy / Q000378:metabolism*; D018690:Excitatory Amino Acid Agonists; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects; D005089:Exocytosis / Q000187:drug effects; D006624:Hippocampus / Q000378:metabolism*; D007150:Immunohistochemistry; D066298:In Vitro Techniques; D008297:Male; D051379:Mice; D019599:Mossy Fibers, Hippocampal / Q000187:drug effects; D016202:N-Methylaspartate; D017729:Presynaptic Terminals / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D017661:Receptors, Presynaptic / Q000187:drug effects; D012640:Seizures / Q000139:chemically induced / Q000503:physiopathology; D015032:Zinc / Q000172:deficiency*
D018690:Excitatory Amino Acid Agonists; D017661:Receptors, Presynaptic; D016202:N-Methylaspartate; D015032:Zinc; D002118:Calcium