Caspase inhibitors increase short-term survival of progenitor-cell progeny in the adult rat dentate gyrus following status epilepticus
Caspase inhibitors increase short-term survival of progenitor-cell progeny in the adult rat dentate gyrus following status epilepticus
复制标题
DOI：
10.1046/j.0953-816x.2001.01713.x
复制
发表时间：
2001-09-01
影响因子：
3.4
通讯作者：
Lindvall, O
中科院分区：
文献类型：
--
作者：
Ekdahl, CT;Mohapel, P;Lindvall, O
齿状回(DG)是大脑中为数不多的在整个成年期继续产生新神经元的区域之一。癫痫发作不仅增加神经发生，而且还导致DG神经元死亡。我们通过阻断凋亡细胞死亡的关键成分半胱氨酸氨基转移酶来研究成年大鼠癫痫发作后DG细胞死亡与神经发生的关系。在锂-匹罗卡品致痫持续状态前、致痫后1天、致痫后2 h后1周，侧脑室多次注入caspase抑制剂(pancaspase抑制剂zVADfmk和caspase 3、9抑制剂)，可使致痫1周时颗粒下区末端脱氧核苷酸转移酶介导的荧光素-dUTP缺口末端标记(TUNEL)细胞数减少，溴脱氧尿苷(BrdU)染色的增殖细胞数增加。在癫痫发作后2天或5周，半胱氨酸天冬氨酸氨基转移酶抑制剂治疗组与对照组无差异。我们的发现表明，caspase可能通过调节新生神经元的凋亡来调节癫痫发作诱导的DG中的神经发生，这一作用可以被caspase抑制剂短暂地抑制。此外，尽管先前的研究表明，神经元死亡增加可以触发神经发生，但我们在这里表明，减少凋亡性死亡可能与增加神经发生有关。
The dentate gyrus (DG) is one of the few regions in the brain that continues to produce new neurons throughout adulthood. Seizures not only increase neurogenesis, but also lead to death of DG neurons. We investigated the relationship between cell death and neurogenesis following seizures in the DG of adult rats by blocking caspases, which are key components of apoptotic cell death. Multiple intracerebroventricular infusions of caspase inhibitors (pancaspase inhibitor zVADfmk, and caspase 3 and 9 inhibitor) prior to, just after, 1 day after, and 1 week following 2 h of lithium-pilocarpine-induced status epilepticus reduced the number of terminal deoxynucleotidyl transferase-mediated fluorescein-dUTP nick-end labelled (TUNEL) cells and increased the number of bromodeoxyuridine (BrdU)-stained proliferated cells in the subgranular zone at 1 week. The caspase inhibitor-treated group did not differ from control at 2 days or 5 weeks following the epileptic insult. Our findings suggest that caspases modulate seizure-induced neurogenesis in the DG, probably by regulating apoptosis of newly born neurons, and that this action can be suppressed transiently by caspase inhibitors. Furthermore, although previous studies have indicated that increased neuronal death can trigger neurogenesis, we show here that reduction in apoptotic death may be associated with increased neurogenesis.