Motor neuron degeneration after sciatic nerve avulsion in adult rat evolves with oxidative stress and is apoptosis

J Neurobiol. 1999 Aug;40(2):185-201.

Abstract

The mechanisms for motor neuron degeneration and regeneration in adult spinal cord following axotomy and target deprivation are not fully understood. We used a unilateral sciatic nerve avulsion model in adult rats to test the hypothesis that retrograde degeneration of motor neurons resembles apoptosis. By 21 days postlesion, the number of large motor neurons in lumbar spinal cord was reduced by approximately 30%. The death of motor neurons was confirmed using the terminal transferase-mediated deoxyuridine triphosphate-biotin nick-end labeling method for detecting fragmentation of nuclear DNA. Motor neuron degeneration was characterized by aberrant accumulation of perikaryal phosphorylated neurofilaments. Structurally, motor neuron death was apoptosis. Apoptotic motor neurons undergo chromatolysis followed by progressive cytoplasmic and nuclear condensation with chromatin compaction into uniformly large round clumps. Prior to apoptosis, functionally active mitochondria accumulate within chromatolytic motor neurons, as determined by cytochrome c oxidase activity. These dying motor neurons sustain oxidative damage to proteins and nucleic acids within the first 7 days after injury during the progression of apoptosis, as identified by immunodetection of nitrotyrosine and hydroxyl-modified deoxyguanosine and guanosine. We conclude that the retrograde death of motor neurons in the adult spinal cord after sciatic nerve avulsion is apoptosis. Accumulation of active mitochondria within the perikaryon and oxidative damage to nucleic acids and proteins may contribute to the mechanisms for apoptosis of motor neurons in the adult spinal cord.

Publication types

  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Apoptosis / physiology*
  • DNA Adducts
  • DNA Fragmentation
  • Disease Models, Animal
  • Fluorescent Dyes
  • Humans
  • Immunoenzyme Techniques
  • Male
  • Microscopy, Electron
  • Mitochondria / physiology
  • Motor Neuron Disease / pathology
  • Motor Neurons / pathology*
  • Neurofilament Proteins / metabolism
  • Oxidative Stress
  • Phosphorylation
  • Protein Processing, Post-Translational
  • Rats
  • Rats, Sprague-Dawley
  • Retrograde Degeneration*
  • Sciatic Nerve / injuries*
  • Sciatic Nerve / pathology
  • Spinal Cord / pathology*
  • Stilbamidines*

Substances

  • 2-hydroxy-4,4'-diamidinostilbene, methanesulfonate salt
  • DNA Adducts
  • Fluorescent Dyes
  • Neurofilament Proteins
  • Stilbamidines