Pirttilä Terhi J, Manninen Anni, Jutila Leena, Nissinen Jari, Kälviäinen Reetta, Vapalahti Matti, Immonen Arto, Paljärvi Leo, Karkola Kari, Alafuzoff Irina, Mervaala Esa, Pitkänen Asla
A. I. Virtanen Institute for Molecular Sciences, University of Kuopio, Kuopio, Finland.
Ann Neurol. 2005 Aug;58(2):211-23. doi: 10.1002/ana.20545.
Human temporal lobe epilepsy (TLE) is associated with cellular alterations (eg, hilar cell death, neurogenesis, and granule cell dispersion) in the dentate gyrus but their underlying molecular mechanism are not known. We previously demonstrated increased expression of cystatin C, a protease inhibitor linked to both neurodegeneration and neurogenesis, during epileptogenesis in the rat hippocampus. Here, we investigated cystatin C expression in the dentate gyrus in chronic epilepsy and its association with neuronal loss and neurogenesis. In both rats with epilepsy and human patients with TLE, cystatin C expression was increased in glial cells in the molecular layer of the dentate gyrus, being most prominent in cases with granule cell dispersion. In patients with TLE, high cystatin C expression associated with greater numbers of polysialylated neural cell adhesion molecule-positive newborn cells in the molecular layer, although the overall number was decreased, indicating that the newborn cells migrate to abnormal locations in the epileptic dentate gyrus. These data thus demonstrate that cystatin C expression is altered during the chronic phase of epilepsy and suggest that cystatin C plays a role in network reorganization in the epileptic dentate gyrus, especially in granule cell dispersion and guidance of migrating newborn granule cells.
人类颞叶癫痫（TLE）与齿状回中的细胞改变（如门区细胞死亡、神经发生和颗粒细胞分散）有关，但其潜在的分子机制尚不清楚。我们之前证明，在大鼠海马体癫痫发生过程中，胱抑素C（一种与神经退行性变和神经发生均相关的蛋白酶抑制剂）的表达增加。在此，我们研究了慢性癫痫中齿状回中胱抑素C的表达及其与神经元丢失和神经发生的关系。在癫痫大鼠和TLE人类患者中，齿状回分子层的胶质细胞中胱抑素C表达均增加，在颗粒细胞分散的病例中最为显著。在TLE患者中，高胱抑素C表达与分子层中多唾液酸神经细胞粘附分子阳性新生细胞数量增多相关，尽管总体数量减少，这表明新生细胞迁移至癫痫齿状回中的异常位置。因此，这些数据表明，在癫痫慢性期胱抑素C表达发生改变，并提示胱抑素C在癫痫齿状回的网络重组中发挥作用，尤其是在颗粒细胞分散和迁移的新生颗粒细胞的导向方面。
