Ⅱ型局灶性皮质发育不良特征性病变气球细胞及形态异常神经元哺乳动物雷帕霉素靶蛋白异常激活

Activation of mTOR in maldeveloped balloon cells and dysmorphic neurons of type Ⅱ focal corticaldysplasia

目的探讨难治性癫痫相关性Ⅱ型局灶性皮质发育不良（FCD）特征性病变气球细胞及形态异常神经元哺乳动物雷帕霉素靶蛋白（mTOR）是否异常激活。方法2008至2010年福建医科大学附属第一医院神经外科手术的12例FCDⅡ型相关性难治性癫痫患者病灶脑组织为实验组，上述实验组病灶周围的“正常脑组织”8例作为对照组。用免疫组织化学染色及免疫荧光双标染色检测p-mTOR（Ser2448）及其下游靶分子p-AKT（Ser473）、p-P70S6K（Thr389）在上述脑组织中的表达及细胞分布情况。结果FCDⅡ型病灶特征性病变气球细胞和形态异常神经元p-mTOR（Ser2448）、p-AKT（Ser473）和p-P70S6K（Thr389）呈不同程度的阳性表达，对照组只有少量的锥体神经元呈弱阳性表达。结论局灶性皮质发育不良特征性病变气球细胞及形态异常神经元mTOR异常激活，可能是其组织学改变及反复癫痫发作的一个重要分子机制。

Objective To investigate whether mammalian target of rapamycin （roTOR） kinase was abnormally activated in maldeveloped balloon cells and dysmorphic neurons of focal cortical dysplasia （FCD） with refractory epilepsy. Methods A total of 12 archival cases of FCD type Ⅱ with medically intractable epilepsy treated between 2008 and 2010 were retrieved. Perilesional brain tissue was used as control specimens （ n = 8 ）. The expression of phosphorylated p-AKT （ Ser473 ） , p-roTOR （ Ser2448 ） and p-P70S6K （Thr389） was investigated by imunocytoehemistry. Results The expression of p-AKT （Ser473） , p-mTOR （Ser2448） and p-P70S6K （Thr389） was found in meldeveloped balloon cells and dysmorphic neurons of FCD. A weak stain in a small amount of pyramid neurons was also found in the control group. Conclusion Abnormal activation of mTOR in maldeveloped balloon cells and dysmorphic neurons of FCD may be a key molecular mechanism underlying the histological changes and repeated seizures.