Apoptosis in the Nervous System: Morphological Features, Methods, Pathology, and Prevention

For nearly 70 years apoptosis has been known to be a form of cell death distinct from necrosis as well as an important regressive event during the normal development of the nervous system. For example, in the chick, mouse, rat and human approxiamately 50% of postmitotic neurons die naturally during embryonic or fetal development. It is generally accepted that neurons die during this period by apoptosis. After the period of naturally occurring cell death, the surviving neurons may undergo degeneration and death due to injury or disease later either during development or in adulthood. Recently, apoptosis has been suggested to be involved in the abnormal neuronal death that occurs following axonal injury or in neurodegenerative diseases such as amyotrophic lateral sclerosis and Alzheimer's. Although little is known about the etiology of these diseases, progress is steadilly being made toward understanding their underlying mechanisms. For diseases of spinal motoneurons, during the past two years gene mutations have been identified in patients with familial amyotrophic lateral sclerosis or spinal muscular atrophy. Furthermore, a number of in vitro, in vivo, and mutant animal models have been developed in order to study the factors which control motoneuron survival and/or death. Here, we review the morphological differences between necrotic and apoptotic cell death and some of the methods used to differentiate the two pathways. We also discuss motoneuron cell death during development, following injury and in disease, and its prevention by different agents, including neurotrophic factors.