組織培養法による神経髄鞘形成および維持時の酵素組織化学的研究—hexose momphosphate shuntの骨髄鞘維持に対する意義

The Hexose Monophosphate Shunt-Its Significance for Maintenance of the Myelin Sheath

　神経組織の種々の疾患にさいし，そのほとんどすべての場合に主となり，あるいは副となつて現われる現象に髄鞘の消失すなわち脱髄demyelinationがある。この現象のからくりには，現在においても未知の問題が多く，ある場合には軸索損傷に基づく二次的変性であり，また他の場合には髄鞘に関連するオリゴデンドログリア，あるいはシュワン細胞の変性によつて生じ，また髄鞘の多層の膜構造における抗体付着現象による脱髄などと複雑な機構がひそんでおり，種々の因子が関係している。この報告は中枢および末梢神経組織を体外にて培養し，髄鞘の形成されていく様子，髄鞘維持に関連する因子，さらに髄鞘の破懐していく有様を連続的に観察し，酵素組織化学的検索の結果より，これらの背景となつている問題の二，三について考えてみたいと思う。

high levels of glucose consumption are a well-known metabolic feature of the nervous system insitu. In culture, nervous tissues are similarlycharacterized. Attempts are described below toanalyss this process in myelinating cultures ofmammalian central and peripheral nervous tissuesthrough histochemical studies of enzymes whichcatalyse glucose oxidation.

Nervous tissues developing in vitro over aperiod of weeks or months show a generally highreactivity of dehydrogenases, diaphorases and cyto-chrome oxidase in both neurons and supportingcells, but the patterns of activity among theseenzymes vary. During myelin formation succinicdehydrogenase and DPN and TPN diaphorases areespecially active in the supporting cells, but theiractivity subsides once the myelin sheath reachescompletion. Cytochrome oxidase however main-tains a continuous activity during later maintenanceof the myelin.

To determine whether the glycolytic pathwayshifts from the aerobic route and TCA cycle tosome other at this time, glucose-6-phosphate dehy-drogenase and 6-phosphogluconic dehydrogenasewere studied-as a characteristic enzymes in thehexose monophosphate shunt. Reactivity of G-6-P dehydrogenase and 6-P-G dehydrogenase in sup-porting cells diverges from that of diaphorasesafter myelination, and remains high during main-tenance. Thiamine acts as a co-factor at differentsteps in the TCA cycle and in the hexose mono-phosphate shunt. Administration of the antimeta-balite oxythiamine to culture in low concentrationso as to produce a chronic deficiency brings aboutmainly a degeneration of the myelin sheath. Thiscan be interpreted as a blocking of the HMPshunt. For these and other reasons conversionfrom TCA to HMP is thought to be an importantfactor in the maintenance of the myelin sheath.