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

Lee J. Martin, Adeel Kaiser, Ann C. Price

Research output: Contribution to journalArticle

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 ~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.

Original languageEnglish (US)
Pages (from-to)185-201
Number of pages17
JournalJournal of Neurobiology
Volume40
Issue number2
DOIs
StatePublished - Jan 1 1999

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Keywords

  • Amyotrophic lateral sclerosis
  • Axotomy
  • Mitochondria
  • Neuronal cell death
  • Target deprivation

ASJC Scopus subject areas

  • Neuroscience(all)
  • Cellular and Molecular Neuroscience

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