PROGRAMMED CELL DEATH IN THE NERVOUS SYSTEM

我们已经研究了神经系统中的程序性细胞死亡， 细胞凋亡的生化机制。 为了接近紧张的 系统，更敏感和原位的方法来识别细胞 细胞程序性死亡 我们开发了两种新方法， 在显微镜下识别凋亡细胞。 (1)我们发现 胸腺细胞程序性细胞死亡可以在形态学上遵循 Nomarski光学和胸腺细胞死亡类似于神经元细胞 死亡核分裂的形态学分析使我们能够 为了测试细胞死亡是由于产生毒性因子还是由于 失去了保护性因素。利用新的显微镜方法， 鉴定细胞凋亡时，发现异核体中的细胞核 母体细胞的原始和独特的命运，而不是转移 细胞凋亡或细胞核之间的活力。这种新方法也让我们 鉴定凋亡是小脑颗粒细胞死亡的方法 体外MPP +处理后。(2)我们还开发了一种分子 原位测量DNA链断裂的检测方法。这使我们能够 研究动物的大脑在经历神经退行性变化期间， 缺血、MPTP治疗和发育期间。 这种新方法应该 阐明细胞凋亡在发育过程中和各种 神经系统的疾病状态。

We have studied programmed cell death in the nervous system and the biochemical mechanism of apoptosis in general. To approach the nervous system, more sensitive and in situ methods are needed to identify cells undergoing programmed cell death. We have developed two new methods to identify apoptotic cells under the microscope. (1) We have found that thymocyte-programmed cell death can be followed morphologically with Nomarski optics and that the thymocyte death resembles neuronal cell death. The morphologic analysis of nuclear disintegration has allowed us to test whether cell death is due to production of a toxic factor or due to the loss of a protective factor. Using the new microscopic method to identify apoptosis, the nuclei in the heterokaryons were found to follow the original and distinct fate of the parent cells and not to transfer apoptosis nor viability between nuclei. This new method also allowed us to identify apoptosis as the method of cerebellar granule cell death after MPP + treatment in vitro. (2) We have also developed a molecular detection method to measure DNA strand breaks in situ. This allows us to examine brains of animals undergoing neurodegenerative changes during ischemia, MPTP treatment, and during development. This new method should illuminate the role apoptosis plays during development and during various disease states of the nervous system.