Nerve growth factor-induced growth of sympathetic axons into the optic tract of mature mice is enhanced by an absence of p75(NTR) expression

Postganglionic sympathetic axons display a remarkable ability for new colla teral growth in response to local increases in nerve growth factor (NGF). E levating NGF levels within the brain also induces the directional growth of sympathetic axons, but not within myelinated pathways of adult mammals. In this investigation, we provide in vivo evidence that sympathetic axons are capable of NGF-induced collateral growth through the microenvironment of m ature myelinated pathways, especially in the absence of the p75 neurotrophi n receptor (NTR, In transgenic mice over-expressing NGF centrally and expre ssing p75(NTR), only a few varicose sympathetic axons invade the optic trac t after the first month of postnatal life, In other transgenic mice overexp ressing NGF centrally but lacking p75(NTR) expression, the incidence of sym pathetic axons within this myelinated tract substantially increases. Moreov er, numerous unmyelinated sympathetic axons cluster together to form large processes extending through the optic tract; such structures are first seen 8 weeks after birth. Only these large axon bundles display prominent immun ostaining for GAP-43, which is preferentially localized to the sympathetic fibers, since nonmyelinating Schwann cells are not associated with these ax on bundles, These data provide the first direct evidence that sympathetic a xons are indeed capable of NGF-induced collateral growth into myelinated tr acts of mature mammals, and that their continued growth through this microe nvironment is markedly enhanced by the absence of p75(NTR) expression. We p ropose that p75(NTR) among sympathetic axons may either directly or indirec tly limit collateral branching of these fibers in response to increased lev els of NGF. (C) 1999 John Wiley & Sons. Inc.