Galectin-1 deficiency improves axonal swelling of motor neurones in SOD1G93A transgenic mice

Yuko Kobayakawa, Kunihiko Sakumi, Kosuke Kajitani, Toshihiko Kadoya, Hidenori Horie, Jun ichi Kira, Yusaku Nakabeppu

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9 Citations (Scopus)

Abstract

Aims: Galectin-1, a member of the β-galactoside-binding lectin family, accumulates in neurofilamentous lesions in the spinal cords of both sporadic and familial amyotrophic lateral sclerosis (ALS) patients with a superoxide dismutase 1 gene (SOD1) mutation (A4V). The aim of this study was to evaluate the roles of endogenous galectin-1 in the pathogenesis of ALS. Methods: Expression of galectin-1 in the spinal cord of mutant SOD1 transgenic (SOD1G93A) mice was examined by pathological analysis, real-time RT-PCR and Western blotting. The effects of galectin-1 deficiency were evaluated by cross-breeding SOD1G93A mice with galectin-1 null (Lgals1-/-) mice. Results: Before ALS-like symptoms developed in SOD1G93A/Lgals1+/+ mice, strong galectin-1 immunoreactivity was observed in swollen motor axons and colocalized with aggregated neurofilaments. Electron microscopic observations revealed that the diameters of swollen motor axons in the spinal cord were significantly smaller in SOD1G93A/Lgals1-/- mice, and there was less accumulation of vacuoles compared with SOD1G93A/Lgals1+/+ mice. In symptomatic SOD1G93A/Lgals1+/+ mice, astrocytes surrounding motor axons expressed a high level of galectin-1. Conclusions: Galectin-1 accumulates in neurofilamentous lesions in SOD1G93A mice, as previously reported in humans with ALS. Galectin-1 accumulation in motor axons occurs before the development of ALS-like symptoms and is associated with early processes of axonal degeneration in SOD1G93A mice. In contrast, galectin-1 expressed in astrocytes may be involved in axonal degeneration during symptom presentation.

Original languageEnglish
Pages (from-to)227-244
Number of pages18
JournalNeuropathology and Applied Neurobiology
Volume41
Issue number2
DOIs
Publication statusPublished - Feb 1 2015

All Science Journal Classification (ASJC) codes

  • Pathology and Forensic Medicine
  • Histology
  • Neurology
  • Clinical Neurology
  • Physiology (medical)

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