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Volume 17, Number 21,
Issue of November 1, 1997
pp. 8476-8490
Copyright ©1997 Society for Neuroscience
Nerve Growth Factor Treatment Increases Brain-Derived
Neurotrophic Factor Selectively in TrkA-Expressing Dorsal Root Ganglion
Cells and in Their Central Terminations within the Spinal Cord
Received April 23, 1997; revised July 21, 1997; accepted Aug. 12, 1997.
G. J. Michael1,
S. Averill1,
A. Nitkunan2,
M. Rattray3,
D. L. H. Bennett2,
Q. Yan4, and
J. V. Priestley1
1 Department of Anatomy, Faculty of Basic Medical
Sciences, Queen Mary and Westfield College, London 31 4NS, United
Kingdom, Departments of 2 Physiology and
3 Biochemistry, United Medical and Dental Schools, St.
Thomas's Hospital Medical School Campus, London SE1 7EH, United
Kingdom, and 4 Amgen Inc., Amgen Centre, Thousand Oaks,
California 91320-1789
Using immunocytochemistry and in situ hybridization,
we have examined the expression of brain-derived neurotrophic factor (BDNF) and of neurotrophin receptors in dorsal root ganglion cells. In
the adult rat, BDNF mRNA and protein were found mainly in the subpopulation of cells that express the nerve growth factor (NGF) receptor trkA and the neuropeptide calcitonin gene-related peptide (CGRP). NGF increased BDNF within the trkA/CGRP cells to the extent that almost 90% of trkA cells contained BDNF mRNA after intrathecal NGF treatment, and 80-90% of BDNF-expressing cells contained trkA. Non-trkA cells that expressed BDNF included some trkC cells and some
small cells that labeled with the lectin Griffonia
simplicifolia IB4, a marker for cells that do not express trks.
However, very few trkB cells expressed either BDNF mRNA or protein, and
NGF did not increase BDNF expression in non-trkA cells. BDNF protein was anterogradely transported both peripherally and centrally. The
central transport resulted in BDNF immunoreactivity in CGRP containing
terminal arbors in the dorsal horn of the spinal cord, and this
immunoreactivity was increased by NGF treatment. Electron microscopic
analysis revealed that the BDNF immunoreactivity was present in finely
myelinated and unmyelinated axons and in axon terminals, where it was
most concentrated over dense-cored vesicles.
Our data do not support an autocrine or paracrine role for BDNF within
normal dorsal root ganglia, but indicate that BDNF may act as an
anterograde trophic messenger. NGF levels in the periphery could
influence dorsal horn neurons via release of BDNF from primary
afferents.
Key words:
brain-derived neurotrophic factor;
mRNA;
trkA;
trkB;
NGF;
dorsal root ganglion cells;
primary afferent;
calcitonin gene-related
peptide
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