Pirttilä Terhi J, Lukasiuk Katarzyna, Håkansson Katarina, Grubb Anders, Abrahamson Magnus, Pitkänen Asla
A.I. Virtanen Institute for Molecular Sciences, University of Kuopio, PO Box 1627, FIN-70211 Kuopio, Finland.
Neurobiol Dis. 2005 Nov;20(2):241-53. doi: 10.1016/j.nbd.2005.03.006.
Brain damaging insults cause alterations in neuronal networks that trigger epileptogenesis, and eventually lead to the appearance of spontaneous seizures. The present experiments were designed to study the cellular expression and functions of a cysteine proteinase inhibitor, cystatin C, whose gene expression is previously shown to be upregulated in the rat hippocampus during status epilepticus (SE)-induced epileptogenesis. The present data showed that the expression of cystatin C protein increased in the mouse hippocampus 7 days following SE and localized mainly to astrocytes and microglia. Acute neuronal death in the hippocampus at 24 h after SE was reduced in cystatin C-/- mice. Also, the basal level of neurogenesis in the subgranular layer of dentate gyrus was decreased in cystatin C-/- mice compared to wildtype littermates. Interestingly, migration of newly born neurons within the granule cell layer was attenuated in cystatin C-/- mice. These data demonstrate that cystatin C has a role in neuronal death and neurogenesis during SE-induced network reorganization.
脑损伤性刺激会导致神经网络发生改变，进而引发癫痫发生，并最终导致自发性癫痫发作。本实验旨在研究一种半胱氨酸蛋白酶抑制剂——胱抑素C的细胞表达及功能，此前研究表明，在癫痫持续状态（SE）诱导的癫痫发生过程中，胱抑素C的基因表达在大鼠海马体中上调。目前的数据显示，SE后7天，胱抑素C蛋白在小鼠海马体中的表达增加，且主要定位于星形胶质细胞和小胶质细胞。与野生型同窝小鼠相比，胱抑素C基因敲除小鼠在SE后24小时海马体中的急性神经元死亡减少。此外，与野生型同窝小鼠相比，胱抑素C基因敲除小鼠齿状回颗粒下层的神经发生基础水平降低。有趣的是，胱抑素C基因敲除小鼠颗粒细胞层内新生神经元的迁移减弱。这些数据表明，胱抑素C在SE诱导的网络重组过程中的神经元死亡和神经发生中发挥作用。
