Skip to main content
Log in

Nerve growth factor protects adult sensory neurons from cell death and atrophy caused by nerve injury

  • Published:
Journal of Neurocytology

Summary

The reaction of dorsal root ganglia (DRG) neurons to axotomy and its alteration by locally supplied nerve growth factor (NGF) were examined in adult rats. Surgically implanted silicone chambers attached to the severed tip of the sciatic nerve acted as reservoirs capable of providing prolonged access of NGF to the site of injury. The time course of NGF activity within the chambers was determined by using the standard NGF chick DRG bioassay. The fluid from chambers filled with the NGF-saline solution maintained NGF activity for periods up to 6 weeks after implantation. By 9 weeks, however, the fluid from most chambers failed to show any NGF activity in the bioassay.

Experiments were designed to compare the response in adult rats to injury of DRG neurons receiving chambers filled with either NGF-saline or with only saline. The total neuronal counts in the lumbar fourth and fifth DRG at 3 weeks and 6 weeks after sciatic nerve section showed 22% and 16% cell death, respectively, in those injured neurons receiving saline-filled chamber implants. The animals that received chamber implants which contained an NGF-saline solution showed no cell death in the ipsilateral DRG at either 3 or 6 weeks after injury. Morphometric analysis of injured DRG neurons showed evidence of atrophy in the injured neurons which did not receive NGF. The degree of atrophy among all cell sizes was significantly decreased in those injured neurons receiving NGF. At 3 weeks after section the mean volume of injured neurons not treated with NGF was decreased by 28% as compared with only a 13% decrease in neurons treated with NGF. Similar findings were noted in the 6-week studies. NGF treatment did not alter the incidence of classic changes of chromatolysis in the groups of injured neurons receiving either NGF-saline-filled chambers or only saline-filled chambers.

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

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  • Arvidsson, J., Ygge, J. &Grant, G. (1986) Cell loss in lumbar dorsal root ganglia and transganglionic degeneration after sciatic nerve resection in the rat.Brain Research 373, 15–21.

    Google Scholar 

  • Bocchini, F. &Angeletti, P. V. (1968) The nerve growth factor: purification as a 30,000 molecular weight protein.Proceedings of the National Academy of Sciences USA 64, 787–94.

    Google Scholar 

  • Cavanaugh, M. W. (1951) Quantitative effects of the peripheral innervation area on nerves and spinal ganglion cells.Journal of Comparative Neurology 94, 181–218.

    Google Scholar 

  • Cragg, B. G. (1970) What is the signal for chromatolysis?Brain Research 23, 1–21.

    Google Scholar 

  • Csillik, B., Schwab, M. &Thoenen, H. (1985) Transganglionic regulation of central terminals of dorsal root ganglion cells by nerve growth factor.Brain Research 331, 11–15.

    Google Scholar 

  • Fenton, E. L. (1970) Tissue culture assay of nerve growth factor and of specific antiserum.Experimental Cell Research 59, 383–92.

    Google Scholar 

  • Fitzgerald, M., Wall, P. D., Goedert, M. &Emson, P. E. (1985) Nerve growth factor counteracts the neurophysiological effects of chronic sciatic nerve section.Brain Research 332, 131–41.

    Google Scholar 

  • Grafstein, B. (1983) Chromatolysis reconsidered: a view of the reaction of the nerve cell body to axon injury. InNerve, Organ, and Tissue Regeneration: Research Perspectives (edited bySeil, F. J.), pp. 37–50. New York: Academic Press.

    Google Scholar 

  • Grafstein, B. &McQuarrie, I. G. (1978) Role of the nerve cell body in axonal regeneration. InNeuronal Plasticity (edited byCotman, C. W.), pp. 155–95. New York: Raven Press.

    Google Scholar 

  • Hamburger, V., Brunso-Bechtold, J. K. &Yip, J. W. (1981) Neuronal death in the spinal ganglia of the chick embryo and its reduction by nerve growth factor.Journal of Neuroscience 1, 60–70.

    Google Scholar 

  • Hendry, I. A. (1975) The response of adrenergic neurons to axotomy and nerve growth factor.Brain Research 94, 87–97.

    Google Scholar 

  • Jessell, T., Tsunoo, A., Kanazaw, I. &Otsuka, M. (1979) Substance P: Depletion in the dorsal root horn of rat spinal cord after section of the peripheral process of primary sensory neurons.Brain Research 168, 247–59.

    Google Scholar 

  • Johnson, E. M., Gorin, P. D., Brandeis, L. D. &Pearson, J. (1980) Dorsal root ganglion neurons are destroyed by exposure in utero to maternal antibody to nerve growth factor.Science 210, 916–18.

    Google Scholar 

  • Johnson, E. M., Rich, K. M. &Yip, H. K. (1986) The role of NGF in sensory neuronsin vivo.Trends in Neuroscience 9, 33–7.

    Google Scholar 

  • Kessler, J. T. &Black, I. B. (1980) Nerve growth factor stimulates the development of substance P in sensory ganglia.Proceedings of the National Academy of Sciences USA 77, 649–52.

    Google Scholar 

  • Konigsmark, B. E. (1970) Methods for the counting of neurons. InContemporary Research Methods in Neuroanatomy (edited byNauta, W. J. &Ebbesson, S. O. E.), pp. 315–40. New York: Springer-Verlag.

    Google Scholar 

  • Levi-Montalcini, R. &Angeletti, P. V. (1968) Nerve growth factor.Physiological Review 48, 534–69.

    Google Scholar 

  • Lieberman, A. R. (1971) The-axon reaction. A review of the principal features of perikaryal responses to axon injury.International Review of Neurobiology 14, 49–124.

    Google Scholar 

  • Lieberman, A. R. (1974) Some factors affecting retrograde neuronal responses to axonal lesions. InEssays on the Nervous System (edited byBellairs, R. &Gray, E. G.), pp. 71–105. Oxford: Clarendon Press.

    Google Scholar 

  • Nja, A. &Purves, D. (1978) The effects of nerve growth factor and its antiserum on synapses in the superior cervical ganglion of the guinea pig.Journal of Physiology 277, 53–75.

    Google Scholar 

  • Otten, U., Goedert, M., Mayer, N. &Lembeck, F. (1980) Requirement of nerve growth factor for development of substance P-containing neurons.Nature 287, 158–9.

    Google Scholar 

  • Ranson, S. W. (1906) Retrograde degeneration in spinal nerves.Journal of Comparative Neurology 16, 265–93.

    Google Scholar 

  • Rich, K. M., Yip, H. K., Osborne, P. A., Schmidt, R. E. &Johnson, E. M., jr (1984) Role of nerve growth factor in the adult dorsal root ganglia neuron and its response to injury.Journal of Comparative Neurology 230, 110–18.

    Google Scholar 

  • Richardson, P. M. &Riopelle, R. J. (1984) Uptake of nerve growth factor along peripheral and spinal axons of primary sensory neurons.Journal of Neuroscience 4, 1683–9.

    Google Scholar 

  • Schwartz, J. P., Pearson, J. &Johnson, E. M., Jr (1982) Effect of exposure to anti-NGF on sensory neurons of adult rats and guinea pigs.Brain Research 244, 378–81.

    Google Scholar 

  • Stoeckel, K., Schwab, M. E. &Thoenen, H. (1975) Specificity of retrograde transport of nerve growth factor (NGF) in sensory neurons. A biochemical and morphological study.Brain Research 89, 1–14.

    Google Scholar 

  • Thoenen, H. &Barde, Y.-A. (1980) Physiology of nerve growth factor.Physiological Reviews 60, 1284–335.

    Google Scholar 

  • Ygge, J. &Aldskogius, H. (1984) Intercostal nerve transection and its effect on the dorsal root ganglion. A quantitative study on thoracic ganglion cell numbers and sizes in the rat.Experimental Brain Research 55, 402–8.

    Google Scholar 

  • Yip, H. K. &Johnson, E. M., jr (1983) Retrograde transport of nerve growth factor in lesioned goldfish retinal ganglion cells.Journal of Neuroscience 11, 2172–82.

    Google Scholar 

  • Yip, H. K., Rich, K. M., Lampe, P. A. &Johnson, E. M., Jr (1984) The effects of nerve growth factor and its antiserum on the postnatal development and survival after injury of sensory neurons in the rat dorsal root ganglia.Journal of Neuroscience 4, 2986–92.

    Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and permissions

About this article

Cite this article

Rich, K.M., Luszczynski, J.R., Osborne, P.A. et al. Nerve growth factor protects adult sensory neurons from cell death and atrophy caused by nerve injury. J Neurocytol 16, 261–268 (1987). https://doi.org/10.1007/BF01795309

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF01795309

Keywords

Navigation