Volume 17, Number 13,
Issue of July 1, 1997
pp. 5206-5220
Copyright ©1997 Society for Neuroscience
Recovery of Neurofilament Expression Selectively in Regenerating
Reticulospinal Neurons
Received Jan. 21, 1997; revised April 11, 1997; accepted April 15, 1997.
Alan J. Jacobs,
Gary P. Swain,
Joseph A. Snedeker,
Donald S. Pijak,
Laura J. Gladstone, and
Michael E. Selzer
Department of Neurology and David Mahoney Institute for
Neurological Sciences, University of Pennsylvania Medical Center,
Philadelphia, Pennsylvania 19104-4283
During regeneration of lamprey spinal axons, growth cones lack
filopodia and lamellipodia, contain little actin, and elongate much
more slowly than do typical growth cones of embryonic neurons. Moreover, these regenerating growth cones are densely packed with neurofilaments (NFs). Therefore, after spinal hemisection the time
course of changes in NF mRNA expression was correlated with the
probability of regeneration for each of 18 identified pairs of
reticulospinal neurons and 12 cytoarchitectonic groups of spinal projecting neurons. During the first 4 weeks after operation, NF
message levels were reduced dramatically in all axotomized reticulospinal neurons, on the basis of semiquantitative in
situ hybridization for the single lamprey NF subunit (NF-180).
Thereafter, NF expression returned toward normal in neurons whose axons
normally regenerate beyond the transection but remained depressed in
poorly regenerating neurons. The recovery of NF expression in good
regenerators was independent of axon growth across the lesion, because
excision of a segment of spinal cord caudal to the transection site
blocked regeneration but did not prevent the return of NF-180 mRNA. The early decrease in NF mRNA expression was not accompanied by a reduction
in NF protein content. Thus the axotomy-induced loss of most of the
axonal volume resulted in a reduced demand for NF rather than a
reduction in volume-specific NF synthesis. We conclude that the
secondary upregulation of NF message during axonal regeneration in the
lamprey CNS may be part of an intrinsic growth program executed only in
neurons with a strong propensity for regeneration.
Key words:
regeneration;
neurofilaments;
lamprey;
spinal
transection;
reticulospinal;
Müller cells;
Mauthner cells;
cytoskeleton