1989 Fiscal Year Final Research Report Summary
Mechanism of cytoprotection against neuronal damage
| Project/Area Number |
63570372
|
|---|
| Research Category |
Grant-in-Aid for General Scientific Research (C)
|
| Allocation Type | Single-year Grants |
|---|
| Research Field |
Neurology
|
|---|
| Research Institution | University of Occupational and Environmental Health |
|---|
Principal Investigator |
OISHI Tomonari University of Occupational and Environmental Health, Faculty of Medicine, 医学部, 講師 (50038907)
|
|---|
| Project Period (FY) |
1988 – 1989
|
| Keywords | cytoprotection / glutathione / MPTP / cyclohexene-1-one / reserpine / dopamine |
|---|
| Research Abstract |
1. Simultaneous defermination of reduced and oxidized glutathione in the rat brain by high- performance liquid chromatography with electrochemical detection. Reduced and oxidized glutathiones in various regions of the rat brain were measured simultaneously by HPLC with ECD, using a dual Hg / Au electrode thin-layer cell.
2. Effect of reserpine on dopamine and glutathione turnover in the rat brain. Reserpine (2.5 mg/kg, i.p.) increased brain dopamine and its metabolites, DOPAC and HVA. GSH and GSSG levels showed regional distributions: they were low in the hypotalamus, stratum, midbrain and medulla oblongata. Reserpine decreased GSSG / GSH ratio in the stratum. These results suggest that the oxidative stress may be induced by the increase in dopamine turnover and activate glutathione peroxidase system.
3. Effect of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) on amines and glutathione turnover in the mouse brain. MPTP (20 or 40 mg/kg, s.c.) decreased DA, DOPAC and HVA 7 days after the injection in the mouse (C57BL, male, 20g). MPTP caused a transient increase in DA and HVA, but a decrease in DOPAC 1 or 2 hours after the injection. At the same time, GSSG / GSH ratio decreased in the stratum, but increased in the other brain regions. These results indicate that MPTP causes the activation of glutathione peroxidase system in the brain except for the stratum, and this may reflect the selective degeneration of nigro- striatal DA neurons.
4. Effect of MPTP on brain glutathione turnover in the CHX-treated mouse. Cyclohexene-l-one (CHX, 100 mg/kg, i.p.) decreased brain GSH and GSSH in the mouse 3 hours after the injection. MPTP (20 mg/kg, s.c.) increased GSSG / GSH ratio in the stratum in CHX-treated mouse. MPTP decreased GSSG / GSH ratio in the midbrain. These results suggest that GSH level may not be a rate-limiting factor, and the response to oxidative stress is different between in the stratum and in the midbrain.
|
