Accumulation of chondroitin sulfate proteoglycans in the microenvironment of spinal motor neurons in amyotrophic lateral sclerosis transgenic rats

Hideki Mizuno, Hitoshi Warita, Masashi Aoki, Yasuto Itoyama

Research output: Contribution to journalArticlepeer-review

32 Citations (Scopus)

Abstract

Chondroitin sulfate proteoglycans (CSPGs) are the major components of extracellular matrix in the central nervous system. In the spinal cord under various types of injury, reactive gliosis emerges in the lesion accompanied by CSPG up-regulation. Several types of CSPG core proteins and their side chains have been shown to inhibit axonal regeneration in vitro and in vivo. In the present study, we examined spatiotemporal expression of CSPGs in the spinal cord of transgenic (Tg) rats with His46Arg mutation in the Cu/Zn superoxide dismutase gene, a model of amyotrophic lateral sclerosis (ALS). Immunofluorescence disclosed a significant up-regulation of neurocan, versican, and phosphacan in the ventral spinal cord of Tg rats compared with age-matched controls. Notably, Tg rats showed progressive and prominent accumulation of neurocan even at the presymptomatic stage. Immunoblotting confirmed the distinct increase in the levels of both the full-length neurocan and their fragment isoforms. On the other hand, the upregulation of versican and phosphacan peaked at the early symptomatic stage, followed by diminishment at the late symptomatic stage. In addition, double immunofluorescence revealed a colocalization between reactive astrocytes and immunoreactivities for neurocan and phosphacan, especially around residual large ventral horn neurons. Thus, reactive astrocytes are suggested to be participants in the CSPG accumulation. Although the possible neuroprotective involvement of CSPG remains to be investigated, the present results suggest that both the reactive astrocytes and the differential accumulation of CSPGs may create a nonpermissive microenvironment for neural regeneration in neurodegenerative diseases such as ALS.

Original languageEnglish
Pages (from-to)2512-2523
Number of pages12
JournalJournal of Neuroscience Research
Volume86
Issue number11
DOIs
Publication statusPublished - 2008 Aug 15

Keywords

  • Amyotrophic lateral sclerosis
  • Chondroitin sulfate proteoglycan
  • Microenvironment
  • SOD1
  • Transgenic rat

ASJC Scopus subject areas

  • Cellular and Molecular Neuroscience

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