Animal Models of Induced Apoptotic Death in the Substantia Nigra

Apoptosis is a form of cell death in which genetically regulated programs intrinsic to the cell bring about its own demise. In recent years, there has been a tremendous growth of interest in apoptosis as a mechanism of disease in a wide range of human disorders including the neurodegenerative diseases, such as Parkinson’s disease (PD) (1 ). This growth of interest has spawned an extraordinary number of recent discoveries about the molecular basis of apoptosis. It is important to emphasize, however, that much of this new knowledge has been attained in the study of relatively simple systems, such as invertebrate models or mammalian nonneural cell culture systems. Less is known about these mechanisms in neural cells, and much of what is known is based on studies of peripheral neural cells (such as sympathetic ganglia and PC 12 cells) in tissue culture. Much less is known about central neurons; in particular, we know little about the regulation of apoptotic death in central neurons in living animals. It is especially important to try to identify the mechanisms of cell death in central neurons of known phenotype, particularly those implicated in human neurodegenerative disease, such as the dopamine neurons in PD. The purpose of the models we have developed of induced apoptosis in dopamine neurons of the substantia nigra (SN) is to try to translate what is being learned about the molecular mechanisms of apoptosis in simpler systems to these neurons.