Peripheral nerve insult induces NMDA receptor-mediated, delayed degeneration in spinal neurons.
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 continuous 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.
Azkue
J J
JJ
II. Physiologisches Institut, Abeteilung Physiologie des Zentralnervensystems, Universität Heidelberg, Germany.
Zimmermann
M
M
Hsieh
T F
TF
Herdegen
T
T
D000818:Animals; D003714:Denervation; D016291:Dizocilpine Maleate / Q000494:pharmacology; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D005821:Genetic Techniques; D007150:Immunohistochemistry; D008297:Male; D009410:Nerve Degeneration / Q000473:pathology / Q000503:physiopathology*; D016900:Neurofilament Proteins / Q000378:metabolism; D009474:Neurons / Q000502:physiology*; D010750:Phosphoproteins / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors / Q000502:physiology*; D012584:Sciatic Nerve / Q000293:injuries*; D013116:Spinal Cord / Q000473:pathology / Q000503:physiopathology*; D013997:Time Factors; D014950:Wounds, Penetrating / Q000473:pathology / Q000503:physiopathology*
D018691:Excitatory Amino Acid Antagonists; D016900:Neurofilament Proteins; D010750:Phosphoproteins; D016194:Receptors, N-Methyl-D-Aspartate; D016291:Dizocilpine Maleate