Enhanced neurotrophin-induced axon growth in myelinated portions of the CNS in mice lacking the p75 neurotrophin receptor

Axonal growth in the adult mammalian CNS is limited because of inhibitory i nfluences of the glial environment and/or a lack of growth-promoting molecu les. Here, we investigate whether supplementation of nerve growth factor (N GF) to the CNS during postnatal development and into adulthood can support the growth of sympathetic axons within myelinated portions of the maturing brain. We have also asked whether p75(NTR) plays a role in this NGF-induced axon growth. To address these questions we used two lines of transgenic mi ce overexpressing NGF centrally, with or without functional expression of p 75(NTR) (NGF/p75(+/+) and NGF/p75(-/-) mice, respectively). Sympathetic axo ns invade the myelinated portions of the cerebellum, beginning shortly befo re the second week of postnatal life, in both lines of NGF transgenic mice. Despite the presence of central myelin, these sympathetic axons continue t o sprout and increase in density between postnatal days 14 and 100, resulti ng in a dense plexus of sympathetic fibers within this myelinated environme nt. Surprisingly, the growth response of sympathetic fibers into the cerebe llar white matter of NGF/p75(-/-) mice is enhanced, such that both the dens ity and extent of axon ingrowth are increased, compared with age-matched NG F/p75(+/+) mice. These dissimilar growth responses cannot be attributed to differences in cerebellar levels of NGF protein or sympathetic neuron numbe rs between NGF/p75(+/+) and NGF/p75(-/-) mice. Our data provide evidence de monstrating that growth factors are capable of overcoming the inhibitory in fluences of central myelin in the adult CNS and that neutralization of the p75(NTR) may further enhance this growth response.