Peripheral nerve insult induces NMDA receptor-mediated, delayed degeneration in spinal neurons

Authors

  • Jon Jatsu Azkue,

    1. II. Physiologisches Institut, Abteilung Physiologie des Zentralnervensystems, Universität Heidelberg, Im Neuenheimer Feld 326, 69120 Heidelberg, Germany,
    Search for more papers by this author
    • *

      Present address: Department of Neurosciences, School of Medicine and Dentistry, University of the Basque Country, PO Box 699, 48080 Bilbao, Spain.

  • Manfred Zimmermann,

    1. II. Physiologisches Institut, Abteilung Physiologie des Zentralnervensystems, Universität Heidelberg, Im Neuenheimer Feld 326, 69120 Heidelberg, Germany,
    Search for more papers by this author
  • Tsui-Fen Hsieh,

    1. II. Physiologisches Institut, Abteilung Physiologie des Zentralnervensystems, Universität Heidelberg, Im Neuenheimer Feld 326, 69120 Heidelberg, Germany,
    Search for more papers by this author
  • Thomas Herdegen

    1. Institut für Pharmakologie, Klinikum der Christian-Albrechts-Universität zu Kiel, Hospitalstr. 4, 24105 Kiel, Germany
    Search for more papers by this author

Correspondence: Jon Jatsu Azkue, at present address below.

Abstract

Injury of a peripheral nerve gives rise to adaptive functional and structural alterations in spinal neurons. We report that the rearrangement of the spinal circuitry in response to sciatic nerve transection in adult rats involves a delayed mode of degeneration of lumbar spinal cord neurons. Nuclear fragmentation was detected by the TUNEL technique 7 days after sciatic neurectomy but not after 3 or 14 days. Dying cells were preferentially located in the ipsilateral superficial dorsal horn and expressed the neuronal cytoskeletal marker SMI-31. Degeneration was prevented by continous systemic treatment with the NMDA receptor-antagonist MK-801. These data are supportive that apoptosis is induced in spinal neurons in a transsynaptic manner by an early signal from injured afferent fibres via activation of spinal NMDA receptors.

Ancillary