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The Journal of Neuroscience, January 15, 2001, 21(2):363-371
Nerve Growth Factor Antiserum Induces Axotomy-Like Changes in
Neuropeptide Expression in Intact Sympathetic and Sensory Neurons
Annette M.
Shadiack,
Yi
Sun, and
Richard E.
Zigmond
Department of Neurosciences, School of Medicine, Case Western
Reserve University, Cleveland, Ohio 44106-4975
Axonal transection of adult sympathetic and sensory neurons leads
to a decrease in their content of target-derived nerve growth factor
(NGF) and to dramatic changes in the expression of several neuropeptides and enzymes involved in transmitter biosynthesis. For
example, axotomy of sympathetic neurons in the superior cervical ganglion (SCG) dramatically increases levels of galanin, vasoactive intestinal peptide (VIP), and substance P and their respective mRNAs
and decreases mRNA levels for neuropeptide Y (NPY) and tyrosine hydroxylase (TH). Axotomy of sensory neurons in lumbar dorsal root
ganglia (DRG) increases protein and mRNA levels for galanin and VIP and
decreases levels for substance P and calcitonin gene-related peptide
(CGRP). To assess whether reduction in the availability of endogenous
NGF might play an important role in triggering these changes, we
injected nonoperated animals with an antiserum against NGF ( NGF).
NGF increased levels of peptide and mRNA for galanin and VIP in
neurons in both the SCG and DRG. NPY protein and mRNA were decreased in
the SCG, but levels of TH protein and mRNA remained unchanged. In
sensory neurons the levels of SP and CGRP protein decreased after
NGF treatment. These data suggest that the reduction in levels of
NGF in sympathetic and sensory neurons after axotomy is partly
responsible for the subsequent changes in neuropeptide expression.
Thus, the peptide phenotype of these axotomized neurons is regulated
both by the induction of an "injury factor," leukemia inhibitory
factor, as shown previously, and by the reduction in a target-derived
growth factor.
Key words:
axotomy; calcitonin gene-related peptide; dorsal root
ganglion; galanin; leukemia inhibitory factor; NGF; neuropeptide Y; sensory neurons; substance P; superior cervical ganglion; sympathetic
neurons; tyrosine hydroxylase; vasoactive intestinal peptide
Copyright © 2001 Society for Neuroscience 0270-6474/01/212363-09$05.00/0
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