Inhibiting the glycogen synthase kinase-3β activity suppress mossy fiber sprouting and epileptogenesis in pentylenetetrazole kindling rat model of epilepsy

Abstract Background Epilepsy is a chronic neurodegenerative disease. Emerging data have implicated mossy fiber sprouting (MFS) as one of the most common pathological features of epilepsy. Glycogen synthase kinase 3β (GSK-3β), a multifunctional protein kinase, can phosphorylate tau at many sites. Its roles in MFS and epileptogenesis remain to be investigated deeply. Our research is to explore the effects of GSK-3β activity on MFS and tau phosphorylation sites in epileptogenesis. Methods The pentylenetetrazol-kindled rat model was established and the expression of P-tau(Ser396) was measured at 3 days and at 1, 2, 4 and 6 weeks after the first PTZ injection. Then the GSK-3β activity was inhibited by injecting SB216763 into the lateral ventricle in pentylenetetrazol-treated rats. The epileptic-associated behavior, expressions of GSK-3β, P-GSK-3β(s9), P-tau(Ser396) and degree of MFS at several time points were measured in pentylenetetrazol-treated rats with intracerebroventricular injection of SB216763. Results Compared with control group, the expression of P-tau(Ser396) was up-regulated in PTZ group. The GSK-3β activity in pentylenetetrazol-treated rats was inhibited by intracerebroventricular injection of SB216763. With the administration of SB216763, increased expression of P-GSK-3β(s9), decreased expression of P-tau (Ser396) and lesser severity of MFS and seizure were observed in PTZ-treated rat. Conclusions Our findings indicate the GSK-3β activity contributed to formation of MFS and epileptogenesis and tau phosphorylation at the ser396 site may be involved in this process.