Susceptibility to kainate-induced seizures under dietary zinc deficiency.
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 zinc-deficient 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 zinc-deficient 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.
Takeda
Atsushi
A
Department of Medical Biochemistry, School of Pharmaceutical Sciences, University of Shizuoka, Yada, Shizuoka, Japan. takedaa@u-shizuoka-ken.ac.jp
Hirate
Maki
M
Tamano
Haruna
H
Nisibaba
Daisuke
D
Oku
Naoto
N
D000818:Animals; D001921:Brain / Q000187:drug effects / Q000503:physiopathology; D001923:Brain Chemistry / Q000187:drug effects; D003677:Deficiency Diseases / Q000150:complications / Q000503:physiopathology*; D004198:Disease Susceptibility / Q000209:etiology / Q000503:physiopathology; D004305:Dose-Response Relationship, Drug; D005110:Extracellular Space / Q000737:chemistry / Q000378:metabolism; D005526:Food, Formulated; D018698:Glutamic Acid / Q000032:analysis / Q000378:metabolism; D006624:Hippocampus / Q000378:metabolism; D007608:Kainic Acid; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D017551:Microdialysis; D018377:Neurotransmitter Agents / Q000032:analysis / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D012640:Seizures / Q000139:chemically induced* / Q000150:complications / Q000503:physiopathology; D013572:Synaptic Vesicles / Q000378:metabolism / Q000473:pathology; D015032:Zinc / Q000032:analysis / Q000172:deficiency* / Q000378:metabolism; D005680:gamma-Aminobutyric Acid / Q000032:analysis / Q000378:metabolism
D018377:Neurotransmitter Agents; D018698:Glutamic Acid; D005680:gamma-Aminobutyric Acid; D015032:Zinc; D007608:Kainic Acid