Inducible nitric oxide synthase (iNOS) and nitrotyrosine immunoreactivity in the spinal cords of transgenic mice with a G93A mutant SOD1 gene

Shoichi Sasaki, Hitoshi Warita, Koji Abe, Makoto Iwata

Research output: Contribution to journalArticle

37 Citations (Scopus)

Abstract

We performed a prospective, longitudinal immunohistochemical study of the spinal cords of transgenic mice with a G93A mutant SOD1 gene at 4 fixed points in time, using antibodies to inducible nitric oxide synthase (iNOS) and nitrotyrosine. The purpose of this study was to characterize the temporal and topographic distribution of iNOS and nitrotyrosine immunoreactivity in the spinal cord over a certain period, thus illuminating the possible role of increased oxidative damage to the motor system in the neurodegenerative process in this animal model. Specimens from age-matched non-transgenic wild-type mice served as controls. The control mice showed no positive iNOS or nitrotyrosine immunoreactivity in the somata of anterior horn neurons or their neuronal processes at any age. On the other hand, the transgenic mice demonstrated a common immunostaining pattern of iNOS and nitrotyrosine in the anterior horn neurons. When the mice reached the age of 24 wk (early presymptomatic stage), the anterior horn neurons and their neuronal processes were occasionally immunostained for iNOS and nitrotyrosine; at 28 wk (late presymptomatic stage), the anterior horn neurons were not uncommonly immunostained; at 32 wk (early symptomatic stage) and 35 wk (end-stage), positive iNOS and nitrotyrosine immunoreactivity was frequently observed in proliferated reactive astrocytes as well as in the somata of the anterior horn cells. The selective localization of positive iNOS and nitrotyrosine immunoreactivity in the anterior horn neurons suggests that oxidative stress may be involved in the pathomechanism of degeneration of motor neurons in this transgenic animal model.

Original languageEnglish
Pages (from-to)839-846
Number of pages8
JournalJournal of Neuropathology and Experimental Neurology
Volume60
Issue number9
DOIs
Publication statusPublished - Jan 1 2001

Keywords

  • Amyotrophic lateral sclerosis
  • Immunohistochemistry
  • Inducible nitric oxide synthase
  • Nitrotyrosine
  • SOD1 mutation
  • Spinal cord
  • Transgenic mice

ASJC Scopus subject areas

  • Pathology and Forensic Medicine
  • Neurology
  • Clinical Neurology
  • Cellular and Molecular Neuroscience

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