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Volume 16, Number 17,
Issue of September 1, 1996
pp. 5344-5350
Copyright ©1996 Society for Neuroscience
A Distinct Pattern of Trophic Factor Expression in
Myelin-Deficient Nerves of Trembler Mice: Implications for
Trophic Support by Schwann Cells
Received April 4, 1996; revised June 6, 1996; accepted June 11, 1996.
Hana C. Hyman Friedman,
Tony N. Jelsma,
Garth M. Bray, and
Albert J. Aguayo
Centre for Research in Neuroscience, Montréal General
Hospital Research Institute and McGill University, Montréal,
Québec, Canada H3G 1A4
Distal to a peripheral nerve transection, myelin degradation and
Schwann cell (SC) proliferation are accompanied by a marked
upregulation of brain-derived neurotrophic factor (BDNF) and a decrease
of ciliary neurotrophic factor (CNTF) in non-neuronal cells. To
investigate the role of SC differentiation in trophic factor
regulation, we studied BDNF and CNTF expression in sciatic nerves from
Trembler-J (Tr-J) mice. In these animals,
a mutation in the pmp-22 gene causes a failure of
myelination and continuous SC proliferation, but axonal continuity is
preserved. In spite of the severe abnormalities in Tr-J
nerves, BDNF levels remained as low as in the intact controls.
Thus, the primary SC disorder in Tr-J produces a
different pattern of BDNF expression from that caused by axonal
breakdown due to nerve transection. Furthermore, the upregulation of
BDNF mRNA triggered by transection was 70-fold in control nerves, but
only 30-fold in Tr-J sciatic nerves. Because these
results raised the possibility that axonal loss may influence
neurotrophin expression only in SCs that have differentiated toward a
myelinating phenotype, we measured BDNF mRNA after axotomy in the
cervical sympathetic trunk (CST), a predominantly unmyelinated
autonomic nerve. In contrast to the sciatic nerves, the BDNF mRNA level
barely increased in the injured CST, supporting the idea that not all
SCs are equal sources of trophic molecules. In Tr-J
sciatic nerves, CNTF mRNA levels were fourfold lower than normal,
implying that the downregulation of this cytokine is a sensitive
indicator of a spectrum of SC perturbations that affect myelinating
cells.
Key words:
axon-Schwann cell interactions;
Trembler;
demyelination;
CNTF;
BDNF;
injury responses;
Schwann cell
differentiation
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