Restorative Neurology and Neuroscience - Volume 1, issue 3-4

Authors: Burgoyne, Robert D. | Robson, Susanne J.

Article Type: Research Article

Abstract: The expression and distribution of β-tubulin gene products and post-translationally modified forms of α-tubulin in dorsal root ganglion neurons in culture were examined. The neurons in culture rapidly regenerated neurites and expressed multiple β-tubulin genes (Mβ2, Mβ3/4, Mβ5, Mβ6). The gene products were present in the neurites and growth cones. Unmodified tyrosinated α-tubulin was present in the neurites and growth cones but modified α-tubulins (detyrosinated and acetylated) were largely absent from growth cones. The distribution of the α-tubulin forms is consistent with assembly of tubulin occurring behind the growth cone after transport of non-polymeric subunits. Distal assembly of microtubules would …provide a pool of unmodified α-tubulin subunits for the assembly of labile microtubules in the growth cone. Subsequent modification behind the advancing growth cone would stabilise the newly formed neurite. Show more

Keywords: Tubulin, Microtubules, Dorsal root ganglion

DOI: 10.3233/RNN-1990-13401

Citation: Restorative Neurology and Neuroscience, vol. 1, no. 3-4, pp. 173-177, 1990

Authors: Cancalon, Paul F.

Article Type: Research Article

Abstract: The composition and organization of the axonal cytoskeleton vary from neuron to neuron and the ability of a nerve to regenerate may, at least in part, depend on the pre-existing nature of the cytoskeleton. In axons, where the cytoskeletal elements are loosely organized enough material may be mobilized after an injury to allow elongation to proceed. However, if microtubules and neurofilaments interact closely with each other, it may not be possible for enough material to be released from or to migrate through a complex network. As a consequence material is not provided to the growing tip and elongation cannot proceed …beyond the initial sprouting. Show more

Keywords: Cytoskeleton, NFs, MTs, Cytoskeletal interactions, Elongation velocity

DOI: 10.3233/RNN-1990-13402

Citation: Restorative Neurology and Neuroscience, vol. 1, no. 3-4, pp. 179-187, 1990

Authors: Tetzlaff, W. | Bisby, M.A.

Article Type: Research Article

Abstract: Following injury to the facial nerve, facial motoneurons respond with a rapid suppression of neurofilament synthesis, and an increase in actin and tubulin synthesis. In situ hybridization studies show that these changes are the result of alterations in levels of the corresponding mRNAs. The increased ratio of neurofilament to tubulin expression is also characteristic of developing neurons, and direct evidence for the idea that axon injury provokes a partial return to a developmental state is provided by the finding that there is rapid re-expression of a developmentally regulated α-tubulin gene. In magnocellular rubrospinal neurons, whose axons do not regenerate after …injury, the same initial changes in gene expression occurred, but they were not sustained. We do not know whether this is cause or effect of the failure to regenerate, but we can conclude that injured CNS neurons have the potential to respond to injury by initiating a ‘regeneration programme’. Failure to sustain this programme is presumably due to differences in the trophic environment of central and peripheral axons. Show more

Keywords: Cytoskeleton, Regeneration, Cell body reaction, Rubrospinal neurons

DOI: 10.3233/RNN-1990-13403

Citation: Restorative Neurology and Neuroscience, vol. 1, no. 3-4, pp. 189-196, 1990

Authors: Wilson, David L. | Perry, G.W.

Article Type: Research Article

Abstract: We review evidence related to several hypotheses concerning the mechanism of axon regeneration and present new data addressing one hypothesis. That one hypothesis concerns the signal that initiates changes in the cell bodies of neurons after axon damage. We identify a molecule that has a number of the properties expected of such a signal. We also review the hypothesis that induction of some genes is tightly correlated with nerve regeneration, and conclude that such a correlation is not so ‘tight’. Nevertheless, proteins whose rate of synthesis or transport is increased in some systems are good candidates for playing important roles …in regrowth. A third hypothesis, that mammalian CNS neurons fail to regenerate because of a failure to induce growth-associated proteins, is probably not true. Growth-associated proteins appear to be induced, at least transiently, in some cases where regeneration is abortive. The state of the neuron undoubtedly is important in regeneration, but many neurons, even in the CNS, appear to be able to support axon regrowth given the proper environment. Thus, support seems stronger for the view that the environment at the site of damage (including surfaces and growth factors) determines whether significant regrowth occurs in most cases. Show more

Keywords: Nerve regeneration, Axoplasmic transport, Proteins, Two-dimensional gels, Sciatic nerve, Axon growth, Growth-associated proteins

DOI: 10.3233/RNN-1990-13404

Citation: Restorative Neurology and Neuroscience, vol. 1, no. 3-4, pp. 197-203, 1990

Authors: Ishii, Douglas N.

Article Type: Research Article

Abstract: The mechanisms responsible for the formation, loss, and regeneration of vertebrate synapses are still shrouded in mystery. Recent data suggesting that insulin-like growth factor II (IGF-II) may play a special role in the nervous system are reviewed. In particular, studies now show that the IGF-II gene is selectively expressed in a manner consistent with its involvement in the formation of the neural circuitry. The prenatal up-regulation and postnatal down-regulation of IGF-II transcripts in muscle are closely correlated with the prenatal accumulation and postnatal elimination, respectively, of polyneuronal innervation at the neuromuscular junction. Use and disuse of nerve and muscle can …profoundly alter the developmental rate at which superfluous synapses are eliminated. Such alteration may result through modification of the rate at which postnatal down-regulation of IGF-II mRNA content occurs. Moreover, IGF-II mRNA content is correlated with the capacity of muscle to regenerate synapses. The IGF-II gene may be the first example of a gene which can regulate the development and turnover of vertebrate synapses. Show more

Keywords: Somatomedin, Neuromuscular junction, Synaptogenesis

DOI: 10.3233/RNN-1990-13405

Citation: Restorative Neurology and Neuroscience, vol. 1, no. 3-4, pp. 205-210, 1990

Authors: Kanje, Martin | Skottner, Anna | Sjöberg, Jacob

Article Type: Research Article

Abstract: We have found that insulin-like growth factor I (IGF-I) stimulates regeneration of the rat sciatic nerve. This paper reviews and adds some new data to our investigations on the effects of local administration of IGF-I to the sciatic nerve after infliction of a crush or freeze injury.

Keywords: Insulin-like growth factors, Somatomedins, Peripheral nerve, Sciatic nerve, Rat, Regeneration

DOI: 10.3233/RNN-1990-13406

Citation: Restorative Neurology and Neuroscience, vol. 1, no. 3-4, pp. 211-215, 1990

Authors: Raivich, Gennadij | Hellweg, Rainer | Graeber, Manuel B. | Kreutzberg, Georg W.

Article Type: Research Article

Abstract: Growth factors and their receptors play a central role in the regulation of normal and injury-induced regenerative cell growth. In this article we review the data on the expression of growth factor receptors for β-nerve growth factor, platelet-derived growth factor and serum transferrin during regeneration following peripheral nerve injury. Particular emphasis is put on the pathophysiological mechanisms leading to the expression of these growth factor receptors, their interaction with their respective ligands and their specific role in this regenerative process.

Keywords: Peripheral nerve regeneration, NGF receptor, PDGF receptor, Transferrin receptor, Schwann cell, Fibroblast

DOI: 10.3233/RNN-1990-13407

Citation: Restorative Neurology and Neuroscience, vol. 1, no. 3-4, pp. 217-223, 1990

Authors: Carlsen, Richard C. | De Leon, Marino | Tetzlaff, Wolfram | Parhad, Irma M. | Bisby, Mark A.

Article Type: Research Article

Abstract: We are interested in the role cyclic AMP may play as a mediator of growth factor-induced gene expression in regenerating peripheral nerves. As a first step, we investigated mRNA levels and protein synthesis in intact frog dorsal root ganglia (DRG) treated with the adenylate cyclase activator, forskolin in vitro. Forskolin (10−7 M) increased intraganglionic cyclic AMP concentration 3-fold within 40 min of application and maintained this concentration through 60 min, when the drug was withdrawn. Addition of forskolin to isolated DRG neurons for 1 h increased the incorporation of [3 H]leucine into TCA-insoluble material beginning 12 h after the …withdrawal of forskolin. Axonally transported labeled material was increased almost 2-fold by 12 h. The effect of forskolin could be blocked by the simultaneous addition of actinomycin D, but not if actinomycin D was added 1 h later. Northern and dot-blot analysis of RNA extracted from the treated ganglia indicated that an mRNA coding for an α-subunit of tubulin was increased by treatment with forskolin. 2D PAGE also demonstrated an increase in an α-subunit of tubulin. An increase in neuronal cyclic AMP appears to selectively increase the production of specific proteins and may contribute to the production of macromolecules involved in the initiation and stimulation of axonal regeneration. Show more

Keywords: Frog DRG, Protein synthesis, Cyclic AMP, Forskolin, Nerve regeneration

DOI: 10.3233/RNN-1990-13408

Citation: Restorative Neurology and Neuroscience, vol. 1, no. 3-4, pp. 225-232, 1990

Authors: Skottner, Anna | Kanje, Martin | Arrhenius-Nyberg, Vibeke | Lundborg, Göran

Article Type: Research Article

Abstract: Systemic administration of human growth hormone (hGH) to intact or hypophysectomized rats was found to stimulate regeneration of the crush-lesioned sciatic nerve. The IGF-I levels of serum of the treated rats did not correlate with regeneration of the nerve but hGH treatment increased the IGF-I content of the nerve. The results suggest that a GH-mediated increase of IGF-I in the sciatic nerve could be involved in the stimulatory effect of GH on neurite outgrowth.

Keywords: Human growth hormone, Insulin-like growth factors, Sciatic nerve, In vivo, Regeneration, Rats

DOI: 10.3233/RNN-1990-13409

Citation: Restorative Neurology and Neuroscience, vol. 1, no. 3-4, pp. 233-235, 1990

Authors: Gispen, W. H. | Boonstra, J. | De Graan, P. N. E. | Jennekens, F. G. I. | Oestreicher, A. B. | Schotman, P. | Schrama, L. H. | Verhaagen, J. | Margolis, F.L.

Article Type: Research Article

Abstract: The protein kinase C substrate B-50 is identical to the growth-associated protein GAP-43. Although as yet no causal relationship has been established between B-50/GAP-43 and neurite outgrowth, evidence accumulates that the function of the protein relates to neuronal plasticity. Stimulation of PC12 cells by NGF results in translocation of the protein from cytosolic stores to the membrane of newly formed neurite-like extensions. The protein is associated with the inner leaflet of the growth cone membrane isolated from neonatal rat brain and was used as a marker to study the development of the rat pyramidical tract and olfactory system. In the …adult rat, crush lesion of the sciatic nerve results in a rapid expression of B-50/GAP-43 mRNA followed by synthesis of B-50/GAP-43 protein in dorsal root ganglia and transport of the protein into the newly formed sprouts. Presumably, the neurotrophic effect of melanocortins on peripheral nerve repair is not brought about by enhancement of B-50/GAP-43 synthesis per se. Bulbectomy (central) or Triton X-100 lesioning (peripheral) of the olfactory epithelium results in a differential expression of B-50/GAP-43 and the olfactory marker protein characterizing two stages in the regeneration of this epithelium. Evidence that the degree of phosphorylation may co-determine the role of B-50/GAP-43 in neurite outgrowth is discussed. Show more

Keywords: B-50/GAP-43, Axonal regeneration, Neuronal development, Sciatic nerve, Pyramidal tract, Olfactory system, Melanocortins, Protein kinase C

DOI: 10.3233/RNN-1990-13410

Citation: Restorative Neurology and Neuroscience, vol. 1, no. 3-4, pp. 237-244, 1990