発生-発達期のアミノ酸系神経シグナルかく乱による遅発性中枢毒性発現の解明 : —幼若期雄マウスへのイボテン酸投与による成長後の脳高次機能障害について—

概要

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To demonstrate the induction of the delayed central nervous toxicity by disturbing neuronal activities in the developing brain, we administered a single oral dose of ibotenic acid (one of the mushroom toxin: 1 mg/kg), a potent glutamate receptor agonist, to the pregnant female mice at the gestational day of 14.5, infant male mice at 2 weeks old and adult male mice at 11 weeks old. The deviances of anxiety-related behaviors, impairment of memory and depleted information processing capability were suggested in male mice dosed with ibotenic acid at the juvenile stage by our behavioral analysis constructed by openfield test, light and dark transition test, elevated plus-maze test, contextual and cued fear conditioning test and auditory startle response/prepulse inhibition test. The overgrowth of neural processes and impairment of synaptic distribution were detected in the hippocampus of these mice. Gene expression analysis of mouse hippocampus by percellome methods indicated that the axonal repulsion and spine formation were affected by oral intake of ibotenic acid at the juvenile stage.