Changes in immunoreactivity for growth associated protein-43 suggest reorganization of synapses on spinal sympathetic neurons after cord transection
Section snippets
Experimental procedures
All protocols for these experiments were approved by the University of Western Ontario Animal Care Committee in accordance with the policies established in the Guide to the Care and Use of Experimental Animals prepared by the Canadian Council on Animal Care. Fifty-four adult male Wistar rats (Charles River, St Constance, Quebec, Canada), weighing approximately 250–350 g, were prepared for surgical interventions by sedation with 2.5 mg/kg Diazepam (i.p.) 10 min prior to anaesthesia with sodium
Light microscopy
GAP-43 immunoreactivity was found in fibres in all thoracic spinal segments in rats with intact spinal cords. In horizontal sections of spinal cord, clearly defined immunoreactive fibres extended rostrocaudally along the intermediolateral gray matter, forming several dense clusters in each cord segment (Fig. 1). These clusters usually surrounded FluoroGold- or NADPH-diaphorase-labelled SPN in the IML (Fig. 1B). The fibres immunoreactive for GAP-43 formed a ladder-like pattern in the gray
Discussion
We have demonstrated a major change in the distribution of GAP-43 immunoreactivity in the IML and in the intermediate gray matter as a result of complete transection of the upper thoracic spinal cord. In the intact cord, GAP-43-immunoreactive fibres were organized in a regular, ladder-like pattern in autonomic areas of the spinal gray matter and these GAP-43-containing fibres synapsed on retrogradely labelled SPN. Within 30 days of transection, this orderly arrangement of GAP-43-immunoreactive
Conclusions
We have demonstrated a striking change in the pattern of GAP-43 immunoreactivity in the intermediolateral gray matter caudal to a cord transection that is consistent with remodelling of synaptic inputs to SPN. The ladder-like arrangement of GAP-43 immunoreactivity in the intact cord was replaced by a reticular network of GAP-43-immunoreactive fibres coinciding with the appearance of GAP-43 immunoreactivity in the somata of spinal neurons. These findings suggest that intraspinal neurons with
Acknowledgements
This research was supported by grants from the Heart and Stroke Foundation of Ontario (T2679), the Medical Research Council of Canada and the National Health and Medical Research Council of Australia. L. C. Weaver is the recipient of a Career Investigator award from the Heart and Stroke Foundation of Ontario; I. J. Llewellyn-Smith is a Senior Research Fellow of the National Health and Medical Research Council of Australia; A. V. Krassioukov held a Fellowship from the Medical Research Council of
References (56)
- et al.
The expression of GAP-43 in relation to neuronal growth and plasticity: when, where, how, and why?
Prog. Brain Res.
(1991) - et al.
Catecholamines enzymes and neuropeptides are expressed in fibres and somata in the intermediate grey matter in chronic spinal rats
Neuroscience
(1997) - et al.
Serotonergic terminals express a growth-associated protein (GAP-43) in the adult rat spinal cord
Neurosci. Lett.
(1994) - et al.
The recovery of postural reflexes and locomotion following low thoracic hemisection in adult cats involves compensation by undamaged primary afferent pathways
Expl Neurol.
(1993) - et al.
Distribution of immunoreactivity for enkephalin, substance P and vasoactive intestinal peptide in fibres surrounding splanchnic sympathetic preganglionic neurons in rats
Neuroscience
(1993) - et al.
Identification of spinal interneurons antecedent to adrenal sympathetic preganglionic neurons using trans-synaptic transport of herpes simplex virus type 1
Neuroscience
(1995) Neuropeptide Y-like immunoreactivity in cat spinal cord with special reference to autonomic areas
Brain Res.
(1987)- et al.
Delivery of a foreign gene to sympathetic preganglionic neurons using recombinant herpes simplex virus
Neuroscience
(1995) - et al.
GAP 43-like immunoreactivity in normal adult rat sciatic nerve, spinal cord, and motoneurons; axonal transport and effect of spinal cord transection
Neuroscience
(1993) - et al.
Glutamate-immunoreactive synapses on retrogradely-labelled sympathetic preganglionic neurons in rat thoracic spinal cord
Brain Res.
(1992)
The tungstate-stabilized tetramethylbenzidine reaction for light and electron microscopic immunocytochemistry and for revealing biocytin-filled neurons
J. Neurosci. Meth.
B-50 (GAP-43) in the rat spinal cord caudal to hemisection: lack of intraspinal sprouting by dorsal root axons
Neurosci. Lett.
Intracellular recording from sympathetic preganglionic neurons in cat lumbar spinal cord
Brain Res.
A comparison between the adult rat and neonate rat of the architecture of sympathetic preganglionic neurones projecting to the superior cervical ganglion, stellate ganglion and adrenal medulla
J. auton. nerv. Syst.
Neuronal pathfinding is abnormal in mice lacking the neuronal growth cone protein GAP-43
Cell
Depletion of 43-kD growth-associated protein in primary sensory neurons leads to diminished formation and spreading of growth cones
J. Cell Biol.
Absence of persistent spreading, branching, and adhesion in GAP-43-depleted growth cones
J. Cell Biol.
On the distribution of GAP-43 and its relation to serotonin in adult monkey and cat spinal cord and lower brainstem
Eur. J. Neurosci.
Distribution of GAP-43 mRNA in the brain stem of adult rats as evidenced by in situ hybridization: localization within monoaminergic neurons
J. Neurosci.
Nitric oxide synthetase (NOS)-containing sympathoadrenal cholinergic neurons of the rat IML-cell column: Evidence from histochemistry, immunohistochemistry and retrograde labelling
J. comp. Neurol.
Growth cone morphology varies with position in the developing mouse visual pathway from retina to first targets
J. Neurosci.
Redistribution of GAP-43 during growth cone development in vitro; immunocytochemical studies
J. Neurocytol.
GAP-43 distribution is correlated with development of growth cones and presynaptic terminals
J. Neurocytol.
Spinal cord lamina V and lamina VII interneuronal projections to sympathetic preganglionic neurons
J. comp. Neurol.
Brainstem and bulbospinal neurotransmitter systems in the control of blood pressure
J. Hypertens.
GAP-43 expression in primary sensory neurons following central axotomy
J. Neurosci.
Up-regulation of GAP-43 and growth of axons in rat spinal cord after compression injury
J. Neurocytol.
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