Improved survival of injured sciatic nerve Schwann cells in mice lacking the p75 receptor.

Following nerve injury, there is a dramatic increase in the expression of the p75 neurotrophin receptor on Schwann cells (Heumann, R., Korsching, S., Bandtlow, C. and Thoenen, H., Changes of nerve growth factor synthesis in non-neuronal cells in response to sciatic nerve transection. J. Cell Biol., 104 (1987) 1623-1631. Taniuchi, M., Clark, H.B., Schweitzer, J.B. and Johnson, E.M., Expression of nerve growth factor by Schwann cells of axotomized peripheral nerves: ultrastructural location, suppression by axonal contact, and binding properties. J. Neurosci., 8 (1988) 664-681.), however the role of the p75 receptor following injury remains unclear. Previous studies have shown that the p75 receptor may play a role in the apoptosis of several cell types. To better understand the role of the p75 receptor in the events following nerve injury, we have compared apoptosis in injured sciatic nerves of adult mice lacking functional p75 receptors and Balb-C (wild-type) mice. Following sciatic nerve crush or resection injuries, we used a fluorescent FragEL DNA fragmentation method to examine the extent of cellular apoptosis in distal nerve segments 5 days, 21 days and 4 months later. Nerve injury induced large numbers of apoptotic nuclei in nerves of both strains, but in p75 knockout mice, the density of apoptotic cells was lower compared to Balb-C mice, 21 days following injury. The p75 receptor may promote apoptosis in Schwann cells when axons are regenerating into the denervated nerve stump.