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Journal of Neuroscience, Vol 11, 2528-2544, Copyright © 1991 by Society for Neuroscience
Response of facial and rubrospinal neurons to axotomy: changes in mRNA expression for cytoskeletal proteins and GAP-43
W Tetzlaff, SW Alexander, FD Miller and MA Bisby
Departments of Anatomy, University of Calgary, Alberta, Canada.
Neurons confined within the mammalian CNS usually do not regenerate after
axonal injury, while axonal regeneration is the rule in the PNS. It has
been hypothesized that this may be related to differences in the
microenvironment of the PNS versus CNS and to differences in the neuronal
response to injury. In order to test the latter hypothesis, we compared
changes in gene expression after axotomy in two populations of neurons: rat
facial motoneurons and rat rubrospinal neurons. In situ hybridization with
cDNA probes for the medium and light neurofilament protein revealed a
reduced mRNA content in both facial and rubrospinal neurons at all times
investigated (i.e., 1, 2, and 3 weeks after axotomy). On the other hand,
mRNAs for actin and tubulin were increased in both neuronal populations
during the first week after axotomy. While this increase was sustained in
facial motoneurons for several weeks, total tubulin mRNA and actin mRNA
were decreased in rubrospinal neurons at 2 and 3 weeks after axotomy,
coincident with their atrophy. The developmentally regulated T alpha 1
tubulin mRNA, which was previously shown to be reexpressed in facial
motoneurons after axotomy, was elevated severalfold in axotomized
rubrospinal neurons, and increased levels persisted in some rubrospinal
neurons as late as 7 weeks after axotomy. Similarly, the developmentally
regulated GAP-43 mRNA increased in both axotomized facial and rubrospinal
neurons, and increased levels were sustained in some axotomized rubrospinal
neurons for at least 7 weeks. The response of rubrospinal neurons to
axotomy in the cervical spinal cord is, in the first week, qualitatively
similar to the response of facial motoneurons. However, by 2 weeks after
axotomy there is a generalized reduction in mRNA levels for all three
cytoskeletal proteins that is associated with neuronal atrophy. During this
period, mRNA levels for the two specific markers of the growth state, T
alpha 1 tubulin and GAP-43, remain elevated. Thus, axotomy of rubrospinal
neurons appears to set in motion two independent events. First, an axotomy
signal initiates a cell-body reaction similar to that of PNS neurons,
including increased mRNA levels for T alpha 1 tubulin and GAP- 43. Later, a
generalized cellular atrophy and decrease in mRNA levels occur without
reversing the specific responses of T alpha 1 and GAP-43 to axotomy. We
conclude that the failure of rubrospinal neurons to regenerate is not due
to a failure to initiate gene-expression changes characteristic of
regenerating peripheral neurons.(ABSTRACT TRUNCATED AT 400 WORDS)
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