[Changes in GAT-3 and GABA-T mRNA expression of C6 glioma cells in response to a 2-week treatment with sodium valproate and withdrawal].

OBJECTIVE

To examine the effects of sodium valproate(VPA) treatment and withdrawal on the expression of GABA transporter-3 (GAT-3) and GABA transaminase (GABA-T) mRNA in C6 glioma cells, and to explore the role of GAT-3 and GABA-T in the rebound mechanism of VPA withdrawal.

METHODS

C6 glioma cells were maintained for 2 weeks in DMEM medium containing VPA (50 mg/L) to establish the cell model of chronic exposure to VPA. Semi-quantitative RT-PCR was used to examine the changes of GAT-3 and GABA-T mRNA expression in response to VPA treatment and withdrawal.

RESULTS

Chronic exposure to VPA down-regulated GAT-3 mRNA expression to 39.1% +/-0.5% from 46% +/-1.3% in the control group; After VPA withdrawal, GAT-3 mRNA expression level kept decreasing, reaching the minimum (11.7% +/-1.6%) 24 h after the withdrawal and with an increase to the level of 33.5%+/-1.1% after another 24 hr. GABA-T mRNA expression was up-regulated to 71.31% +/-8.39% from 34.77% +/-2.36% of the control level after VPA treatment, the withdrawal of which resulted in decreased GABA-T mRNA expression. Till 12 h after the withdrawal, the GABA-T mRNA expression level decreased to the minimum, 25.36% +/-7.68%.

CONCLUSIONS

Chronic treatment with VPA can down-regulate GAT-3 mRNA expression and up-regulate GABA-T mRNA expression in C6 glioma cells, and this undulation may involve VPA withdrawal rebound.