Ep系マウスにおける腦アセチルコリンの研究

Acetylcholine metabolism in the ep strain of mouse

I．はじめに

　われわれが脳のアセチルコリン（ACh）代謝に興味をいだいたのは，はじめ加藤^9）によつてep系マウスの脳におけるAChの量的異常が示されたことに端を発している。その後の研究を通じてepマウスにおけるAChの変化は，このマウスの特徴である先天性痙攣素因を理解するための有力な資料のひとつであると同時に，より一般的な視野から脳のACh代謝を検討する場合にも，好都合な材料であることが推定されるようになつた。本稿では加藤，矢部，町山および筆者の協同実験においてえられた所見を中心とし，また他の研究室からの報告をも参照して，epマウスにおけるACh代謝の異常を要約してみた。

Aspects of brain metabolism in a special strain of convulsive mouse (ep strain) is reviewed, with special reference to abnormalities in the ACh metabolism. Generalised tonus-clonus is induced in the ep mouse by applying gentle stimulation which causes loss of postural equi-librium of the animal; the convulsive characteristic appears to be hereditary as a Mendelian dominant. Factors affecting the convulsive predisposition are described. The level of ACh in the ep brain as a whole is higher by approximately 50 per cent than in control strains, in determinations with both decapitated (Table 1) and frozen animals (Table 4). This is practically attributable to an increase of osmotically-labile fraction of the particle-bound ACh which is more than doubled in comparison with that of control strains (Table 2). In contrast, the level of osmotically-stable fraction of particle-bound ACh is fairly constant among strains. Evidence is presented which indicates that changes in thelabile ACh are responsible for the decrease and increase of ACh accompanying convulsions and anaesthesia respectively (Table 4). Exhaustion of labile ACh only is expected to occur during maximal convulsive activity (Fig. 1), and restoration of labile ACh after ep- and electro-convulsions is preceded by a transient rise in the level of stable ACh. The choline acylase activity in ep brain is higher by about 50 per cent than that of control stains (Fig. 2), which appears to furnish an explanation for the higher value of ACh in situ. ACh formation in the sliced brain tissue is also higher in the ep mouse, in both low and high potassium media (Table 5). AChE activity of the cerebral cortex from the non-convulsed ep mouse is slightly enhanced (Fig. 3), but this can be reduced to three-fourths by convulsing the animal once a week with postural stimulation (Fig. 4). A possibility of metabolic approach to convulsive -disposition as well as an availability of the ep mouse in the study of ACh regulation in the brain are discussed.