Quantitative immunocytochemical analysis of the spinal cord in G86R superoxide dismutase transgenic mice: Neurochemical correlates of selective vulnerability

Brett M. Morrison, Jon W. Gordon, Michael E. Ripps, John Morrison

Research output: Contribution to journalArticle

79 Scopus citations

Abstract

Transgenic mice with a G86R mutation in the mouse superoxide dismutase (SOD-l) gene, which corresponds to a mutation that has been observed in familial amyotrophic lateral sclerosis (ALS), display progressive loss of motor function and provide a valuable model of ALS. The pathology in the spinal cords of these mice was evaluated to determine whether there are chemically identified populations of neurons that are either highly vulnerable or resistant to degeneration. Qualitatively, there were phosphorylated neurofilament protein (NFP)immunoreactive inclusions and a pronounced loss of motoneurons in the ventral horn of the spinal cord without the presence of vacuoles that has been reported in other SOD-1 transgenic mice. Neuron counts from SOD-1 and control spinal cords revealed that the percentage loss of NFP-, choline acetyltransferase (CHAT)-, and calretinin (CR)-immunoreactive neurons was greater than the percentage loss of total neurons, suggesting that these neuronal groups are particularly vulnerable in SOD-1 transgenic mice. In contrast, calbindin-containing neurons did not degenerate significantly and represent a protected population of neurons. Quantitative double-labeling experiments suggested that the vulnerability of CHAT- and CR-immunoreactive neurons was due primarily to the presence of NFP within a subset of these neurons, which degenerated preferentially to CHAT- and CR-immunoreactive neurons that did not colocalize with NFP. Our findings suggest that NFP, which has been demonstrated previously to be involved mechanistically in motoneuron degeneration, may also be important in the mechanism of degeneration that is initiated by the SOD-1 mutation.

Original languageEnglish (US)
Pages (from-to)619-631
Number of pages13
JournalJournal of Comparative Neurology
Volume373
Issue number4
DOIs
StatePublished - Sep 30 1996
Externally publishedYes

Keywords

  • amyotrophic lateral sclerosis
  • calbindin
  • motoneuron
  • neurofilament
  • stereology

ASJC Scopus subject areas

  • Neuroscience(all)

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