Early and selective pathology of light chain neurofilament in the spinal cord and sciatic nerve of G86R mutant superoxide dismutase transgenic mice

Brett M. Morrison, I. Wei Shu, Amy L. Wilcox, Jon W. Gordon, John Morrison

Research output: Contribution to journalArticle

21 Citations (Scopus)

Abstract

Pathologic accumulation of neurofilament protein (NF), both within spheroids of the proximal axon and within inclusions of motor neuron somata, is a hallmark of neurodegeneration in amyotrophic lateral sclerosis (ALS). Transgenic mice that express mutations in super-oxide dismutase (SOD-1), which were genetically linked to familial ALS, develop symptomatology and pathology that strongly resemble ALS and therefore provide a useful model for studying the disease. Examining NF in the G86R mutant SOD-1 transgenic mice, we previously demonstrated that phosphorylated NF accumulates in motor neuron somata of symptomatic transgenic mice. In the present study, we expand these results by examining the immunocytochemical distribution of the three subunits of NF (i.e., light, medium, and heavy chains) as well as tubulin in presymptomatic and symptomatic SOD-1 transgenic mice. Although all NF subunits, but not tubulin, accumulate along with phosphorylated NF in the spinal cord inclusions of symptomatic mice, numerous inclusions containing only light chain NF are found in the spinal cord of presymptomatic SOD-1 transgenic mice. In addition to these results in the spinal cord, intensely immunoreactive aggregates of NF-L, but not the other NF subunits or tubulin, were observed in the sciatic nerve of both symptomatic and presymptomatic mutant SOD-1 transgenic mice. These results suggest that the mechanism of NF alteration in SOD-1 transgenic mice, and also perhaps in ALS patients, originates with the disruption of NF-L, only later involving the other subunits. (C) 2000 Academic Press.

Original languageEnglish (US)
Pages (from-to)207-220
Number of pages14
JournalExperimental Neurology
Volume165
Issue number2
DOIs
StatePublished - Jan 1 2000
Externally publishedYes

Fingerprint

Neurofilament Proteins
Spinal Nerves
Intermediate Filaments
Sciatic Nerve
Transgenic Mice
Superoxide Dismutase
Spinal Cord
Pathology
Light
Amyotrophic Lateral Sclerosis
Tubulin
Protein Subunits
Carisoprodol
Motor Neurons
Oxides
Axons
Mutation
neurofilament protein L

Keywords

  • Amyotrophic lateral sclerosis
  • Cytoskeleton
  • Electron microscopy
  • Motor neurons
  • Neurodegeneration
  • Neurofilament
  • Sciatic nerve

ASJC Scopus subject areas

  • Neurology
  • Developmental Neuroscience

Cite this

Early and selective pathology of light chain neurofilament in the spinal cord and sciatic nerve of G86R mutant superoxide dismutase transgenic mice. / Morrison, Brett M.; Shu, I. Wei; Wilcox, Amy L.; Gordon, Jon W.; Morrison, John.

In: Experimental Neurology, Vol. 165, No. 2, 01.01.2000, p. 207-220.

Research output: Contribution to journalArticle

@article{032928cd168343788dc4731edfdcbf20,
title = "Early and selective pathology of light chain neurofilament in the spinal cord and sciatic nerve of G86R mutant superoxide dismutase transgenic mice",
abstract = "Pathologic accumulation of neurofilament protein (NF), both within spheroids of the proximal axon and within inclusions of motor neuron somata, is a hallmark of neurodegeneration in amyotrophic lateral sclerosis (ALS). Transgenic mice that express mutations in super-oxide dismutase (SOD-1), which were genetically linked to familial ALS, develop symptomatology and pathology that strongly resemble ALS and therefore provide a useful model for studying the disease. Examining NF in the G86R mutant SOD-1 transgenic mice, we previously demonstrated that phosphorylated NF accumulates in motor neuron somata of symptomatic transgenic mice. In the present study, we expand these results by examining the immunocytochemical distribution of the three subunits of NF (i.e., light, medium, and heavy chains) as well as tubulin in presymptomatic and symptomatic SOD-1 transgenic mice. Although all NF subunits, but not tubulin, accumulate along with phosphorylated NF in the spinal cord inclusions of symptomatic mice, numerous inclusions containing only light chain NF are found in the spinal cord of presymptomatic SOD-1 transgenic mice. In addition to these results in the spinal cord, intensely immunoreactive aggregates of NF-L, but not the other NF subunits or tubulin, were observed in the sciatic nerve of both symptomatic and presymptomatic mutant SOD-1 transgenic mice. These results suggest that the mechanism of NF alteration in SOD-1 transgenic mice, and also perhaps in ALS patients, originates with the disruption of NF-L, only later involving the other subunits. (C) 2000 Academic Press.",
keywords = "Amyotrophic lateral sclerosis, Cytoskeleton, Electron microscopy, Motor neurons, Neurodegeneration, Neurofilament, Sciatic nerve",
author = "Morrison, {Brett M.} and Shu, {I. Wei} and Wilcox, {Amy L.} and Gordon, {Jon W.} and John Morrison",
year = "2000",
month = "1",
day = "1",
doi = "10.1006/exnr.2000.7457",
language = "English (US)",
volume = "165",
pages = "207--220",
journal = "Experimental Neurology",
issn = "0014-4886",
publisher = "Academic Press Inc.",
number = "2",

}

TY - JOUR

T1 - Early and selective pathology of light chain neurofilament in the spinal cord and sciatic nerve of G86R mutant superoxide dismutase transgenic mice

AU - Morrison, Brett M.

AU - Shu, I. Wei

AU - Wilcox, Amy L.

AU - Gordon, Jon W.

AU - Morrison, John

PY - 2000/1/1

Y1 - 2000/1/1

N2 - Pathologic accumulation of neurofilament protein (NF), both within spheroids of the proximal axon and within inclusions of motor neuron somata, is a hallmark of neurodegeneration in amyotrophic lateral sclerosis (ALS). Transgenic mice that express mutations in super-oxide dismutase (SOD-1), which were genetically linked to familial ALS, develop symptomatology and pathology that strongly resemble ALS and therefore provide a useful model for studying the disease. Examining NF in the G86R mutant SOD-1 transgenic mice, we previously demonstrated that phosphorylated NF accumulates in motor neuron somata of symptomatic transgenic mice. In the present study, we expand these results by examining the immunocytochemical distribution of the three subunits of NF (i.e., light, medium, and heavy chains) as well as tubulin in presymptomatic and symptomatic SOD-1 transgenic mice. Although all NF subunits, but not tubulin, accumulate along with phosphorylated NF in the spinal cord inclusions of symptomatic mice, numerous inclusions containing only light chain NF are found in the spinal cord of presymptomatic SOD-1 transgenic mice. In addition to these results in the spinal cord, intensely immunoreactive aggregates of NF-L, but not the other NF subunits or tubulin, were observed in the sciatic nerve of both symptomatic and presymptomatic mutant SOD-1 transgenic mice. These results suggest that the mechanism of NF alteration in SOD-1 transgenic mice, and also perhaps in ALS patients, originates with the disruption of NF-L, only later involving the other subunits. (C) 2000 Academic Press.

AB - Pathologic accumulation of neurofilament protein (NF), both within spheroids of the proximal axon and within inclusions of motor neuron somata, is a hallmark of neurodegeneration in amyotrophic lateral sclerosis (ALS). Transgenic mice that express mutations in super-oxide dismutase (SOD-1), which were genetically linked to familial ALS, develop symptomatology and pathology that strongly resemble ALS and therefore provide a useful model for studying the disease. Examining NF in the G86R mutant SOD-1 transgenic mice, we previously demonstrated that phosphorylated NF accumulates in motor neuron somata of symptomatic transgenic mice. In the present study, we expand these results by examining the immunocytochemical distribution of the three subunits of NF (i.e., light, medium, and heavy chains) as well as tubulin in presymptomatic and symptomatic SOD-1 transgenic mice. Although all NF subunits, but not tubulin, accumulate along with phosphorylated NF in the spinal cord inclusions of symptomatic mice, numerous inclusions containing only light chain NF are found in the spinal cord of presymptomatic SOD-1 transgenic mice. In addition to these results in the spinal cord, intensely immunoreactive aggregates of NF-L, but not the other NF subunits or tubulin, were observed in the sciatic nerve of both symptomatic and presymptomatic mutant SOD-1 transgenic mice. These results suggest that the mechanism of NF alteration in SOD-1 transgenic mice, and also perhaps in ALS patients, originates with the disruption of NF-L, only later involving the other subunits. (C) 2000 Academic Press.

KW - Amyotrophic lateral sclerosis

KW - Cytoskeleton

KW - Electron microscopy

KW - Motor neurons

KW - Neurodegeneration

KW - Neurofilament

KW - Sciatic nerve

UR - http://www.scopus.com/inward/record.url?scp=0033802366&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0033802366&partnerID=8YFLogxK

U2 - 10.1006/exnr.2000.7457

DO - 10.1006/exnr.2000.7457

M3 - Article

VL - 165

SP - 207

EP - 220

JO - Experimental Neurology

JF - Experimental Neurology

SN - 0014-4886

IS - 2

ER -