During normal development of many vertebrate species, substantial numbers of neurons in the central and peripheral nervous system undergo naturally occurring (or programmed) cell death. For example, approximately 50 of spinal motoneurons degenerate and die at a time when these cells are establishing synaptic connections with their target muscles in the chick, mouse, rat, and human. It is generally thought that the survival of developing motoneurons depends on access to trophic molecules. Motoneurons that survive the period of programmed cell death may also die following injury in the developing or adult animal. Increasing evidence suggests that glial-cell-line-derived neurotrophic factor (GDNF) plays a physiological and/or pharmacological role in the survival of various neuronal cell types, including motoneurons. In this paper, we review the survival and growth-promoting effects of GDNF on spinal motoneurons during the period of programmed cell death and following injury.
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