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Accumulation of chondroitin sulfate proteoglycans in the microenvironment of spinal motor neurons in amyotrophic lateral sclerosis transgenic rats
Author(s) -
Mizuno Hideki,
Warita Hitoshi,
Aoki Masashi,
Itoyama Yasuto
Publication year - 2008
Publication title -
journal of neuroscience research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.72
H-Index - 160
eISSN - 1097-4547
pISSN - 0360-4012
DOI - 10.1002/jnr.21702
Subject(s) - perineuronal net , chondroitin sulfate proteoglycan , glial scar , versican , spinal cord , amyotrophic lateral sclerosis , microbiology and biotechnology , chondroitin sulfate , biology , central nervous system , aggrecan , neuroscience , pathology , chemistry , spinal cord injury , anatomy , proteoglycan , extracellular matrix , medicine , glycosaminoglycan , articular cartilage , alternative medicine , disease , osteoarthritis
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 up‐regulation 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. © 2008 Wiley‐Liss, Inc.