Biochemical approach to the pathogenesis of uremic neuropathy --- Neurotoxicity of uremic toxins as determined by tissue culture method ---

Research Project

Project/Area Number	60570375
Research Category	Grant-in-Aid for General Scientific Research (C)
Allocation Type	Single-year Grants
Research Field	Neurology
Research Institution	THE JIKEI UNIVERSITY SCHOOL OF MEDICINE
Principal Investigator	MIYAHARA TADASHI THE JIKEI UNIVERSITY SCHOOL OF MEDICINE professor, 医学部, 教授 (70056456)
Co-Investigator(Kenkyū-buntansha)	KARASHIMA HITOSHI THE JIKEI UNIVERSITY SCHOOL OF MEDICINE Assistant, 医学部, 助手 (00169658) IMAI TAKEO THE JIKEI UNIVERSITY SCHOOL OF MEDICINE Assistant, 医学部, 助手 (80138718)
Project Period (FY)	1985 – 1986
Project Status	Completed (Fiscal Year 1986)
Budget Amount *help	¥1,400,000 (Direct Cost: ¥1,400,000) Fiscal Year 1986: ¥300,000 (Direct Cost: ¥300,000) Fiscal Year 1985: ¥1,100,000 (Direct Cost: ¥1,100,000)
Keywords	uremic neuropathy / uremic toxin / tissue culture method / myelin galactolipid / CNPase / Methylguanidine / メチルグアニジン / グアニジノコハク酸
Research Abstract	To clarify the pathogenesis of uremic neuropathy, the neurotoxicity of uremic toxin was studied by means of tissue culture method. The dorsal root ganglion of fetal mouse was planted in a collagen coated dish and incubated under 5% <CO_2> at 36 C. An in vitro assay of developemental study for the myelination of peripheral nerve was performed morphologically and biochemically. In the electronmicroscopy a compact myelin was observed at the third or fourth week of culture. Those myelin galactolipid as cerebroside and sulfatide and CNPase activity both increased its synthesis and enzyme activity in accord with the morphelogical changes described above. Under the same experimental condition changes of galactolipids of myelin was determined by adding uremic human sera, normal sera methylguanidine(MG), guanidino succinic acid(GSA). There were no changes of myelin galactolipid with addition of MG and GSA and 10 to 20% low concentration of uremic sera. In 80% concentration of uremic sera in medium the synthesis of cerebroside was inhibited while the contol sera in medium increased its synthesis. From above results it was postulated that either a ceratin uremic toxin other than MG and GSA played a role for the pathogenesis of uremic neuropathy or uremic sera contained unknown factor to inhibit myelin synthesis as observed adding normal sera in medium.