Abstracts

Rationale: Hyperactivated mTORC was observed in many diseases with the epileptic seizure, including type II Focal cortical dysplasia (FCD). It is an open question of whether mTORC hyperactivity is the direct reason or the side effect of the epileptic seizure. To answer this question, shutdown mTORC activity in defective neuron serves as a test to detect the necessity of mTORC activity in an epileptic seizure. However, mTOR inhibitor (Rapamycin or Everolimus) cannot efficiently and specifically inhibit mTOR activity in defective neurons. While a peptide inhibitor of mTOR blocks the recruitment of mTOR to the lysosome to block mTOR activity. Methods: The inducible vector of mTORC inhibitor was delivered together with DepDC5 gRNA vector (the FCD model we developed in rat system with a spontanous epileptic seizure, Hu et al., 2018) into the developing lateral ventricle. In the 2-month-old animal, the regular epileptic seizure was observed as we described (Hu et al., 2018). Then, the expression of mTORC inhibitor was induced by Tamoxifen. Results: The phosphorylation of ribosome protein S6, an mTOR downstream protein, was detected with immunostaining and the signal decreased dramatically. It indicated the hyperactivity of mTOR in those defective neurons was mostly shut down.EEG was performed to record brain activity and seizure. After the induction of mTOR inhibitor, the epileptic seizure frequency dramatically decreased, with interictal decreased also. Conclusions: Combined all these results, a conclusion can be getting that hyperactivity of mTORC in FCD rat does cause the epileptic seizure. Our result indicates a possibility to target hyperactivated mTOR to block the seizure in type II FCD. Funding: No funding