Presence of Cu/Zn superoxide dismutase [SOD] immunoreactivity in neuronal hyaline inclusions in spinal cords from mice carrying a transgene for Gly93Ala mutant human Cu/Zn SOD

Noriyuki Shibata, Asao Hirano, Makio Kobayashi, Mauro C. Dal Canto, Mark E. Gurnev, Takashi Komori, Takahiko Umahara, Kohtaro Asayama

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Abstract

This investigation deals with the immunocytochemical localization of Cu/Zn superoxide dismutase (SOD) in the spinal cord neurons of transgenic mice that overexpress Gly93Ala mutant human Cu/Zn SOD and demonstrate clinicopathological features similar to human amyotrophic lateral sclerosis (ALS) with Cu/Zn SOD mutation. At low magnification of light microscopy, the gray and white matter of the spinal cord of Gly93Ala mice showed more intense Cu/Zn SOD immunoreactivity than that of control mice. At higher magnification, the cytoplasm of control mice neurons displayed a distinct staining for Cu/Zn SOD, whereas the surrounding neuropil was only weakly stained. In contrast, the intensity of Cu/Zn SOD immunoreactivity in the cytoplasm of the majority of Gly93Ala mice neurons was similar to that in the neuropil. Almost all neuronal hyaline inclusions (NHIs) of Gly93Ala mice were positively immunostained by antibodies to Cu/Zn SOD, ubiquitin and phosphorylated neurofilament protein (NFP), the intensities of which were much higher in the NHIs than in the surrounding cytoplasm. In control mice, significant Cu/Zn SOD precipitation was not observed to be limited to any particular region of the neuronal cytoplasm. Intracytoplasmic vacuoles in the neuronal soma and processes of Gly93Ala mice were not stained by any of these antibodies. These results indicate that Cu/Zn SOD colocalizes with ubiquitin and phosphorylated NFP in NHIs of mice expressing mutant Cu/Zn SOD; similar findings have been shown for Lewy body-like inclusions of familial ALS patients with Cu/Zn SOD mutation. Moreover, our results point to the possibility that Cu/Zn SOD mutation may have a role in the abnormal Cu/Zn SOD accumulation in the NHIs, in association with motor neuron degeneration.

Original languageEnglish (US)
Pages (from-to)136-142
Number of pages7
JournalActa Neuropathologica
Volume95
Issue number2
DOIs
StatePublished - 1998

Fingerprint

Hyalin
Transgenes
Spinal Cord
Cytoplasm
Neurofilament Proteins
Neuropil
Ubiquitin
Neurons
Superoxide Dismutase-1
Mutation
Lewy Bodies
Nerve Degeneration
Antibodies
Amyotrophic Lateral Sclerosis
Carisoprodol
Motor Neurons
Vacuoles
Transgenic Mice
Microscopy

Keywords

  • Amyotrophic lateral sclerosis
  • Hyaline inclusions
  • Immunocytochemistry
  • Superoxide dismutase
  • Transgenic mouse model

ASJC Scopus subject areas

  • Clinical Neurology
  • Pathology and Forensic Medicine
  • Neuroscience(all)

Cite this

Presence of Cu/Zn superoxide dismutase [SOD] immunoreactivity in neuronal hyaline inclusions in spinal cords from mice carrying a transgene for Gly93Ala mutant human Cu/Zn SOD. / Shibata, Noriyuki; Hirano, Asao; Kobayashi, Makio; Dal Canto, Mauro C.; Gurnev, Mark E.; Komori, Takashi; Umahara, Takahiko; Asayama, Kohtaro.

In: Acta Neuropathologica, Vol. 95, No. 2, 1998, p. 136-142.

Research output: Contribution to journalArticle

Shibata, Noriyuki ; Hirano, Asao ; Kobayashi, Makio ; Dal Canto, Mauro C. ; Gurnev, Mark E. ; Komori, Takashi ; Umahara, Takahiko ; Asayama, Kohtaro. / Presence of Cu/Zn superoxide dismutase [SOD] immunoreactivity in neuronal hyaline inclusions in spinal cords from mice carrying a transgene for Gly93Ala mutant human Cu/Zn SOD. In: Acta Neuropathologica. 1998 ; Vol. 95, No. 2. pp. 136-142.
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abstract = "This investigation deals with the immunocytochemical localization of Cu/Zn superoxide dismutase (SOD) in the spinal cord neurons of transgenic mice that overexpress Gly93Ala mutant human Cu/Zn SOD and demonstrate clinicopathological features similar to human amyotrophic lateral sclerosis (ALS) with Cu/Zn SOD mutation. At low magnification of light microscopy, the gray and white matter of the spinal cord of Gly93Ala mice showed more intense Cu/Zn SOD immunoreactivity than that of control mice. At higher magnification, the cytoplasm of control mice neurons displayed a distinct staining for Cu/Zn SOD, whereas the surrounding neuropil was only weakly stained. In contrast, the intensity of Cu/Zn SOD immunoreactivity in the cytoplasm of the majority of Gly93Ala mice neurons was similar to that in the neuropil. Almost all neuronal hyaline inclusions (NHIs) of Gly93Ala mice were positively immunostained by antibodies to Cu/Zn SOD, ubiquitin and phosphorylated neurofilament protein (NFP), the intensities of which were much higher in the NHIs than in the surrounding cytoplasm. In control mice, significant Cu/Zn SOD precipitation was not observed to be limited to any particular region of the neuronal cytoplasm. Intracytoplasmic vacuoles in the neuronal soma and processes of Gly93Ala mice were not stained by any of these antibodies. These results indicate that Cu/Zn SOD colocalizes with ubiquitin and phosphorylated NFP in NHIs of mice expressing mutant Cu/Zn SOD; similar findings have been shown for Lewy body-like inclusions of familial ALS patients with Cu/Zn SOD mutation. Moreover, our results point to the possibility that Cu/Zn SOD mutation may have a role in the abnormal Cu/Zn SOD accumulation in the NHIs, in association with motor neuron degeneration.",
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