Springer Nature is making SARS-CoV-2 and COVID-19 research free. View research | View latest news | Sign up for updates

Increased expression of phosphotyrosine after axotomy in the dorsal motor nucleus of the vagus nerve and the hypoglossal nucleus


To investigate the role of tyrosine kinase underlying glial cell proliferation after axotomy, the localization of phosphotyrosine was studied immunohistochemically in the dorsal motor nucleus of the vagus nerve and the hypoglossal nucleus after nerve transection in adult rats. An anti-phosphotyrosine antibody weakly stained the cytoplasm of the neurons and some glial cells on the control side of both nuclei, while preferentially staining the plasma membrane of perineuronal microglial cells and neurons weakly on the severed side 2 days after axotomy and intensely between 3 and 7 days. Some of the microglial cells reacted positively with both anti-bromodeoxyuridine and antiphosphotyrosine antibodies, suggesting that tyrosine kinase is involved in microglial cell proliferation. Proliferation of numerous microglial cells was observed in the severed nuclei between 2 and 4 days after axotomy, while only a few were detected on days 5 and 7. These findings suggest that tyrosine kinase is involved in not only the proliferation of perineuronal microglial cells but also in some retrograde neuronal reactions such as differentiation and regeneration.

This is a preview of subscription content, log in to check access.


  1. 1.

    Aldskogius H (1982) Glial cell responses in the adult rabbit dorsal motor vagal nucleus during axon reaction. Neuropathol Applied Neurobiol 8: 341–349

  2. 2.

    Aldskogius H, Barron KD, Regal R (1980) Axon reaction in dorsal motor vagal and hypoglossal neurons of the adult rat. Light microscopical and RNA cytochemistry. J Comp Neurol 193: 165–177

  3. 3.

    Araujo DM, Cotman CW (1992) Basic FGF in astroglial, microglial, and neuronal cultures: characterization of binding sites and modulation of release by lymphokines and trophic factors. J Neurosci 12: 1668–1678

  4. 4.

    Armstrong DM, Brady R, Hersh LB, Hayes RC, Wiley RG (1991) Expression of choline acetyltransferase and nerve growth factor receptor within hypoglossal motoneurons following nerve injury. J Comp Neurol 304: 596–607

  5. 5.

    Aubry M, Maness PF (1988) Developmental regulation of protein tyrosine phosphorylation in rat brain. J Neurosci Res 21: 473–479

  6. 6.

    Cantley LC, Auger KR, Carpenter C, Duckworth B, Graziani A, Kapeller R, Soltoff S (1991) Oncogene and signal transduction. Cell 64: 281–302

  7. 7.

    Ernfors P, Rosario CM, Merlio J-P, Grant G, Aldskogius H, Persson H (1993) Expression of mRNA for neurotrophin receptors in the dorsal root ganglion and spinal cord during development and following peripheral or central axotomy. Mol Brain Res 17: 217–225

  8. 8.

    Fischer EH, Charbonneau H, Tonks NK (1991) Protein tyrosine phosphatase: a diverse family of intracellular and transmembrane enzymes. Science 253: 401–406

  9. 9.

    Graeber MB, Tetzlaff W, Streit WJ, Kreutzberg GW (1988) Microglial cells but not astrocytes undergo mitosis following rat facial nerve axotomy. Neurosci Lett 85: 317–321

  10. 10.

    Hutchins JB, Jefferson VE (1992) Developmental distribution of platelet-derived growth factor in the mouse central nervous system. Dev Brain Res 67: 121–135

  11. 11.

    Ignelzi MA, Padilla SS, Warder DE, Maness PF (1992) Altered expression of pp60c-src induced by peripheral nerve injury. J Comp Neurol 315: 171–177

  12. 12.

    Kato H, Wanaka A, Tohyama M (1992) Co-localization of basic fibroblast growth factor-like imunoreactivity and its receptor mRNA in the rat spinal cord and the dorsal root ganglion. Brain Res 576: 351–354

  13. 13.

    LeBeau JM, Tedeschi B, Walter G (1991) Increased expression of pp60c-src protein-tyrosine kinase during peripheral nerve regeneration. J Neurosci Res 28: 299–309

  14. 14.

    Lieberman AR (1971) The axon reaction: a review of the principal features of perikaryal responses to axon injury. Int Rev Neurobiol 14: 49–124

  15. 15.

    Mannoji H, Yeger H, Becker LE (1986) A specific histochemical marker (lectin Ricinus communis agglutinin-1) for normal human microglia, and application to routine histopathology. Acta Neuropathol (Berl) 71: 341–343

  16. 16.

    Moss AM, Unger JW, Moxley RT, Livingston JN (1990) Localization of phosphotyrosine-containing proteins by immunocytochemistry in the rat forebrain corresponds to the distribution of the insulin receptor. Proc Natl Acad Sci USA 87: 4453–4457

  17. 17.

    Pettmann B, Labourdette G, Weibel M, Sensenbrenner M (1986) The brain fibroblast growth factor (FGF) is localized in neurons. Neurosci Lett 68: 175–180

  18. 18.

    Raivich G, Kreutzberg GW (1987) Expression of growth factor receptors in injured nervous tissue. I. Axotomy leads to a shift in the cellular distribution of specific β-nerve growth factor binding in the injured and regenerating PNS. J Neurocytol 16: 689–700

  19. 19.

    Raivich G, Kreutzberg GW (1987) Expression of growth factor receptors in injured nervous tissue. II. Induction of specific platelet-derived growth factor binding in the injured PNS is associated with a breakdown in the blood-nerve barrier and endothelial interstitial oedema. J Neurocytol 16: 701–711

  20. 20.

    Sasahara M, Fries JW, Raines EW, Gown AM, Westrum LE, Frosch MP, Bonthron DT, Ross R, Collins T (1991) PDGF B-chain in neurons of the central nervous system, posterior pituitary, and in a transgenic model. Cell 64: 217–227

  21. 21.

    Sasahara A, Kott JN, Sasahara M, Raines EW, Ross R, Westrum LE (1992) Platelet-derived growth factor B-chain-like immunoreactivity in the developing and adult rat brain. Dev Brain Res 68: 41–53

  22. 22.

    Shores CG, Maness PF (1989) Tyrosine phosphorylated proteins accumulate in junctional regions of the developing chick neural retina. J Neurosci Res 24: 59–66

  23. 23.

    Smits A, Kato M, Westermark B, Nistér M, Heldin C-H, Funa K (1991) Neurotrophic activity of plastlet-derived growth factor (PDGF): rat neuronal cells possess functional PDGF b-type receptors and respond to PDGF. Proc Natl Acad Sci USA 88: 8159–8163

  24. 24.

    Streit WJ, Graeber MB, Kreutzberg GW (1989) Peripheral nerve lesion produces increased levels of major histocompatibility complex antigens in the central nervous system. J Neuroimmunol 21: 117–123

  25. 25.

    Tillotson ML, Wood JG (1989) Tyrosine phosphorylation in the postnatal rat brain: a developmental, immunohistochemical study. J Comp Neurol 282: 133–141

  26. 26.

    Tilltoson ML, Wood JG (1989) Phosphotyrosine antibodies specifically label ameboid microglia in vitro and ramified microglia in vivo. Glia 2: 412–419

  27. 27.

    Torvik A (1976) Annotation. Central chromatolysis and the axon reaction: a reappraisal. Neuropathol Applied Neurobiol 2: 423–432

  28. 28.

    Wanaka A, Johnson EM, Milbrandt J (1990) Localization of FGF receptor mRNA in the adult rat central nervous system by in situ hybridization. Neuron 5: 267–281

  29. 29.

    Yamada E, Hazama F (1992) Retrograde neuronal degeneration of dorsal motor vagal nucleus after axotomy: ultrastructural investigation. Neuropathology 12: 7–15

  30. 30.

    Yamada E, Hazama F (1993) Different stability of neurofilaments for trypsin treatment after axotomy in the dorsal motor nucleus of vagal nerve and the hypoglossal nucleus. Brain Res 612: 210–215

  31. 31.

    Yarden Y, Ullrich A (1988) Growth factor receptor tyrosine kinase. Annu Rev Biochem 57: 443–478

  32. 32.

    Yeh H-J, Ruit K.G, Wang Y-X, Parks WC, Snider WD, Deuel TF (1991) PDGF A-chain gene is expressed by mammalian neurons during development and in maturity. Cell 64: 209–216

Download references

Author information

Correspondence to Eiji Yamada.

Rights and permissions

Reprints and Permissions

About this article

Cite this article

Yamada, E., Kataoka, H., Isozumi, T. et al. Increased expression of phosphotyrosine after axotomy in the dorsal motor nucleus of the vagus nerve and the hypoglossal nucleus. Acta Neuropathol 88, 14–18 (1994).

Download citation

Key words

  • Axonal reaction
  • Proliferation
  • Phosphotyrosine
  • Neuron
  • Microglia