The Journal of Neuroscience, May 15, 1999, 19(10):4155-4168
Enhanced Neurotrophin-Induced Axon Growth in Myelinated Portions
of the CNS in Mice Lacking the p75 Neurotrophin Receptor
Gregory S.
Walsh1,
Karmen M.
Krol1,
Keith A.
Crutcher2, and
Michael D.
Kawaja1
1 Department of Anatomy and Cell Biology, Queen's
University, Kingston, Ontario, Canada K7L 3N6, and
2 Department of Neurosurgery, University of Cincinnati
Medical Center, Cincinnati, Ohio 45267-0515
Axonal growth in the adult mammalian CNS is limited because of
inhibitory influences of the glial environment and/or a lack of
growth-promoting molecules. Here, we investigate whether
supplementation of nerve growth factor (NGF) 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 p75NTR plays a role in this
NGF-induced axon growth. To address these questions we used two lines
of transgenic mice overexpressing NGF centrally, with or without
functional expression of p75NTR
(NGF/p75+/+ and NGF/p75
/
mice, respectively). Sympathetic axons invade the myelinated portions
of the cerebellum, beginning shortly before the second week of
postnatal life, in both lines of NGF transgenic mice. Despite the
presence of central myelin, these sympathetic axons continue to sprout
and increase in density between postnatal days 14 and 100, resulting in
a dense plexus of sympathetic fibers within this myelinated
environment. Surprisingly, the growth response of sympathetic fibers
into the cerebellar white matter of NGF/p75/
mice is enhanced, such that both the density and extent of axon ingrowth are increased, compared with age-matched
NGF/p75+/+ mice. These dissimilar growth responses
cannot be attributed to differences in cerebellar levels of NGF protein
or sympathetic neuron numbers between NGF/p75+/+ and
NGF/p75/ mice. Our data provide evidence
demonstrating that growth factors are capable of overcoming the
inhibitory influences of central myelin in the adult CNS and that
neutralization of the p75NTR may further enhance
this growth response.
Key words:
nerve growth factor; p75 neurotrophin receptor; myelin; axon growth; sympathetic; cerebellum
Copyright © 1999 Society for Neuroscience 0270-6474/99/19104155-14$05.00/0
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