Ekdahl C T, Mohapel P, Elmér E, Lindvall O
Section of Restorative Neurology, Wallenberg Neuroscience Center, BMC A11, SE-221 84 Lund, Sweden.
Eur J Neurosci. 2001 Sep;14(6):937-45. doi: 10.1046/j.0953-816x.2001.01713.x.
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.
齿状回（DG）是大脑中少数在成年期仍持续产生新神经元的区域之一。癫痫发作不仅会增加神经发生，还会导致DG神经元死亡。我们通过阻断半胱天冬酶（凋亡细胞死亡的关键成分）来研究成年大鼠DG区癫痫发作后细胞死亡与神经发生之间的关系。在锂-匹罗卡品诱导的癫痫持续状态2小时之前、之后、1天后和1周后多次脑室内注入半胱天冬酶抑制剂（泛半胱天冬酶抑制剂zVADfmk以及半胱天冬酶3和9抑制剂），可减少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）细胞的数量，并增加溴脱氧尿苷（BrdU）染色的增殖细胞数量。癫痫发作后2天或5周时，半胱天冬酶抑制剂治疗组与对照组无差异。我们的研究结果表明，半胱天冬酶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区神经发生，并且这种作用可被半胱天冬酶抑制剂短暂抑制。此外，尽管先前的研究表明神经元死亡增加可触发神经发生，但我们在此表明凋亡性死亡的减少可能与神经发生增加有关。
