Biochemical studies on the pathogenetic mechanism of toxic neuropathies by using axonal transport.
Grant-in-Aid for General Scientific Research (C)
|Allocation Type||Single-year Grants |
Pathological medical chemistry
|Research Institution||The University of Tokyo |
KOMIYA Yoshiaki University of Tokyo, Lecturer (Gunma University, Professor), 医学部, 講師 (50010046)
|Project Period (FY)
1986 – 1988
Completed (Fiscal Year 1988)
|Budget Amount *help
¥2,300,000 (Direct Cost: ¥2,300,000)
Fiscal Year 1988: ¥500,000 (Direct Cost: ¥500,000)
Fiscal Year 1987: ¥900,000 (Direct Cost: ¥900,000)
Fiscal Year 1986: ¥900,000 (Direct Cost: ¥900,000)
|Keywords||Axonal transport / Toxic neuropathy / Colchicine / , '-Iminodipropionitrile(IDPN) / 2,5-Hexanedione / Acrylamide / Neurofilament / 微小管 / 2.5-ヘキサンジオン / 二硫化炭素 / 神経毒性 / β, β′-イミノジプロピオニトリル(IDPN) / β,β´-イミノジプロピオニトリル(IDPN)|
Various neurotoxic chemicals are thought to be classified into several groups according to their main targets. Among them three major groups were chosen and in vivo model systems were developed to investigate their biochemical mechanism of action. By analysing slow axonal transport under the influence of these drugs, the following results were obtained.
u. Neurotoxicity of colchicine:
Colchicine completely and exclusively blocks tubulin transport, without affecting that of actin and neurofilament proteins. when 4 g of colchicine is injected into fifth lumbar dorsal root ganglion of 7 week-old rat, almost all unmyelinated axons as well as a small portion of myel-nated ones are degenerated, then start regenerating within 4 days after treatment. At the same time tubulin transport also recovers to normal.
2. Neurotoxicity of , '-iminodipropionitrile:
Neurological symptoms develop a few days after an intraperitoneal injection of IDPN with dose of 1.5g/kg of body weight. Under these conditions axonal transport of neurofilament proteins is severely inhibited, without any disturbance of that of tubulin and actin. Neurofilament transportbecomes normal 6 weeks after IDPN administration, thoughneurological abnormalities never show recovery.
3. Neurotoxicity of acrylamide:
Marked acceleration of all components of slow axonal transport is found in rats after 13 week-administration of acrylamide with dose of 200 ppm in drinking water. This finding is interpreted to be the results of axonal degeneration and regeneration.
4. Neurotoxicity of 2,5-hexanedione:
2, 5-Hexanedione causes an increase of rate of neurofilament transport, leaving that of tubulin and actin unchanged even in early stage of administration when no symptom appears.
5. Neurotoxicity of carbon disulfide:
This drug shows a similar effect on neurofilament transport to that of 2, 5-hexanedione.
Report (4 results)
Research Products (32 results)