Vigabatrin Inhibits Seizures and mTOR Pathway Activation in a Mouse Model of Tuberous Sclerosis Complex
Figure 6
VGB decreased activation of the mTOR pathway in vitro.
A) Western blotting shows P-S6 (Ser 240/244), total S6, and beta-actin expression in primary cultured astrocytes derived from Tsc1GFAPCKO and non-KO control mice. Vehicle or VGB at a dose of 0.06, 0.3 and 0.6 mM was added to the culture medium for 16 hours. Overall, Tsc1GFAPCKO astrocytes showed increased P-S6 expression compared with astrocytes from control mice. VGB blocked the activation of P-S6 in a dose-dependent fashion in both control and KO astrocytes. The ratio of P-S6/total S6 was normalized to the vehicle-treated control group (Cont) or vehicle-treated Tsc1GFAPCKO group (KO). Quantitative summary demonstrates that VGB treatment at doses of 0.3 and 0.6 mM significantly inhibits the activation of P-S6 in astrocytes of both Tsc1GFAPCKO and control mice. B) In contrast to VGB, phenobarbital had no effect on P-S6 expression in control astrocytes at doses that are effective in potentiating GABA-mediated inhibition [25]. *p<0.05, **p<0.01 versus Veh by one-way ANOVA (n = 8 mice/group). Cont = control mice, KO = Tsc1GFAPCKO mice, Veh = vehicle.