Abnormal activation of mammalian target of rapamycin distinguishes type II from type I focal cortical dysplasias with intractable epilepsy

Abstract

Objective To investigate whether mammalian target of rapamycin (mTOR) kinase is abnormally activated in type Ⅱ and type Ⅰ focal cortical dysplasias (FCD) with intractable epilepsy.Methods We investigated the expression of phosphorylated phosphorylated protein kinase B (p-AKT,Ser473),p-mTOR (Ser2448),p-P70S6K (Thr389) in 12 cases of FCD type Ⅱ,12 cases of FCD type Ⅰ and 8 cases of perilesional brain tissue by using immunohistochemistry and immunofluorescence double staining.Resuits The expression of p-AKT (Ser473),p-mTOR (Ser2448),p-P70S6K (Thr389) in FCD type Ⅱ was positive to varying degrees,the expression in FCD type Ⅰ was almost completely negative,and the expression in small amount of pyramid neurons of perilesional brain tissue was weak staining.Conclusion Abnormal activation of mTOR in FCD type Ⅱ may be an important molecular mechanism of the histological changes and repeated seizures,but mTOR is not abnormally activated in FCD type Ⅰ,indicating that FCD type Ⅰ and FCD type Ⅱ may have different pathogenic mechanisms. Key words: Focal cortical dysplasias ; Intractable epilepsy ; Target of rapamycin