Chapter 5 Target derived and putative local actions of neurotrophins in the peripheral nervous system

Abstract

Nerve growth factor (NGF) is the prototype of a family of growth factors including four structurally related proteins known as the neurotrophins. Other members of this family are brain-derived neurotrophic factor (BDNF), neurotrophin-3 (NT-3) and neurotrophin-4/5. In the peripheral nervous system the neurotrophins influence a partially overlapping population of neurons. In in vitro neurite outgrowth or cell survival assays, NGF stimulates embryonic sensory and sympathetic neurons of neural crest origin. BDNF and NT-3 influence certain populations of both neural crest and placode derived sensory neurons. NT-3, but not BDNF, elicits a weak response from sympathetic neurons. It is clear that NGF and BDNF are also important in vivo , because administration of anti-NGF antibodies shortly after the period of cell death substantially increases the loss of spinal sensory neurons, whereas exogenous administration of NGF, or BDNF, at the time of naturally occurring cell death markedly reduces the loss of dorsal root or nodose ganglion neurons. In addition, developing or lesioned motor neurons can be rescued by administration of BDNF.