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Journal of Neuroscience, Vol 13, 3472-3484, Copyright © 1993 by Society for Neuroscience
Differential spatial and temporal gene expression in response to axotomy and deafferentation following transection of the medial forebrain bundle
M Weiser, H Baker, TC Wessel and TH Joh
Cornell University Medical College, W. M. Burke Medical Research Institute, White Plains, New York 10605.
Alterations in the levels of neurotransmitter biosynthetic enzymes are a
concomitant of many neurodegenerative disorders. In order to elucidate
potential mechanisms for longterm alterations in biosynthetic enzyme gene
products in response to neuronal injury, an acute axotomy/deafferentation
model was employed. A unilateral microknife transection of the medial
forebrain bundle (MFB) axotomizes and/or deafferents phenotypically
identified neuronal populations important in the function of the basal
ganglia. Semi-quantitative in situ hybridization and immunohistochemical
analysis demonstrated that the products of the immediate-early gene c-fos
were induced postaxotomy in the noradrenergic neurons of the locus ceruleus
(LC), but not in the dopaminergic neurons of the substantia nigra pars
compacta (SNc). Analysis of the levels of mRNA, protein, and activity for
tyrosine hydroxylase demonstrated that the LC neurons survive the injury
while the SNc neurons degenerate. After MFB transection, Fos protein also
was induced in the corpus striatum within 1 hr, first in large, putatively
cholinergic neuronal populations followed at 3 hr by the small, putatively
GABAergic neurons. The substantia nigra pars reticulata and the subthalamic
nucleus neuronal populations, deafferented by the MFB transection, also
exhibited Fos induction beginning at 3 hr. The data suggest that expression
of Fos in a neuronal population is correlative with respect to cell
survival following either axotomy or deafferentation. Whether Fos induction
following injury is either a necessary mechanism of cell survival or merely
a marker of increased neuronal activity requires further investigation.
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