Neuroprotective Potential of Phase II Enzyme Inducer D3T on Motor Neuron Survival in Vitro

Abstract: In this study， we want to investigate the role of phase II enzyme inducer 3H-1，2-dithiole-3-thione (D3T) on motor neuron survival. The organotypic spinal cord cultures were prepared from 7 day old rat pup lumbar spinal cords. Lumbar spinal cords were collected under sterile conditions， sectioned transversely at 350 mm intervals. Slices were placed on the inserts. After 1 week in culture， the threo-hydroxyaspartate (THA) group， treated with THA alone to achieve a final concentration of 100 mmol/L. For the D3T48h+THA group， tissues were treated with D3T to achieve a final concentration of 15， 30 μmol/L， 48 hour later， the same concentration D3T and 100 μmol/L THA were added to the medium. For the D3T+THA group， tissues were treated with D3T to achieve a final concentration of 15， 30 μmol/L and 100 μmol/L THA were added simultaneously. 0.1%DMSO was added to the drug solubilizer control， no drugs added to the control group. After 4 weeks in culture， tissue were harvested， the number of motor neurons and the ultrastructure of motor neuron were observed by immunohistochemistry and electromicrography. We also compared D3T48h (add D3T 48 h after 7 day culture) group with control (no drug add after 7 day culture) by counting the number of motor neuron. The results showed that D3T can prevent THA-induced motor neuron death， increase motor neuron survival. It suggested that D3T have neuroprotective potential on THA-induced motor neuron death. Phase II enzyme inducer may provide a novel neuroprotective strategy for the treatment of amyotrophic lateral sclerosis.

CSTR: 32200.14.cjcb.2007.01.0027