Levels of nerve growth factor and neurotrophin-3 are affected differentially by the presence of p75 in sympathetic neurons in vivo

The development and survival of sympathetic neurons is critically dependent on the related neurotrophic factors nerve growth factor (NGF) and neurotro phin-3 (NT3), the actions of which must be executed appropriately despite s patial and temporal overlaps in their activities. The tyrosine receptor kin ases, trkA. and trkC, are the cognate receptors for NGF and NT3, respective ly. The p75 neurotrophin receptor has been implicated in neurotrophin bindi ng and signaling for both NGF and NT3. In this study, the authors used mice that overexpressed NGF (NGF-OE) or NT3 (NT3-OE) in skin and mice that lack ed p75 (p75(-/-)) to understand the dynamics of sympathetic neuron response to each neurotrophin and to address the role of p75. NGF and NT3 were meas ured in sympathetic ganglia and skin (a major target of sympathetic neurons ) by using the enzyme-linked immunosorbent assay (ELISA) technique. A three - to four-fold increase in skin NT3 was seen in both NT3-OE and p75(-/-) mi ce. Moreover, both mouse lines exhibited a three-fold increase in ganglioni c NT3. However, the increase in ganglionic NT3 was accompanied by a decreas e in ganglionic NGF in p75(-/-) mice but not in NT3-OE mice. This indicated that p75 plays an important role in determining the level of NGF within sy mpathetic neurons. In NGF-OE mice, the overexpression of NGF was correlated with increased ganglionic NGF and increased ganglionic expression of p75 m RNA. In addition, in NGF-OE mice, ganglionic trkC expression was decreased, as was the amount of NT3 present within sympathetic ganglia. These results indicate that the level of p75 is integral in determining the level of sym pathetic NGF and that NGF competes with NT3 by increasing the expression of p75 and decreasing the expression of trkC. J. Comp. Neurol. 424:99-110, 20 00. (C) 2000 Wiley-Liss, Inc.