Glycobiology Advance Access originally published online on April 19, 2006
Glycobiology 2006 16(8):702-710; doi:10.1093/glycob/cwj115
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N-Acetylglucosamine 6-O-sulfotransferase-1 is required for brain keratan sulfate biosynthesis and glial scar formation after brain injury
2 Department of Biochemistry, Nagoya University Graduate School of Medicine, Nagoya 466-8550, Japan; 3 Department of Health Science, Faculty of Psychological and Physical Sciences, Aichi Gakuin University, Aichi 470-0195, Japan; 4 Department of Ultrastructural Research, National Institute of Neuroscience, National Center of Neurology and Psychiatry, Kodaira, Tokyo 187-8502, Japan; 5 Department of Anatomy, Program in Immunology, University of California, San Francisco, CA 94143; and 6 Institute for Advanced Research, Nagoya University, Furo-cho, Chikusa-ku, Nagoya 464-8601, Japan
1 To whom correspondence should be addressed; e-mail: tmurama{at}dpc.aichi-gakuin.ac.jp/kkadoma{at}med.nagoya-u.ac.jp
Received on December 17, 2005; revised on March 28, 2006; accepted on April 10, 2006
Keratan sulfate (KS) is a glycosaminoglycan composed of repeating disaccharide units with sulfate residues at the C6 positions of galactose and N-acetylglucosamine (GlcNAc). The N-acetylglucosamine 6-O-sulfotransferase(s) (GlcNAc6ST) involved in the synthesis of KS in the central nervous system (CNS) has long been unidentified. Here, we report that a deficiency of GlcNAc6ST-1 leads to loss of 5D4-reactive brain KS and reduction of glial scar formation after cortical stab injury in mice. During the development of mice deficient in GlcNAc6ST-1, KS expression in the brain was barely detectable with the KS-specific antibody 5D4. The reactivity of 5D4 antibody with protein tyrosine phosphatase 
(PTP), a KS proteoglycan (KSPG), was abolished in the deficient mice. In adults, brain injury induced 5D4-reactive KS synthesis in the wounded area in wild-type (WT) mice but not in the deficient mice. Glial scar is formed via the accumulation of reactive astrocytes and is a major obstacle to axonal regeneration by injured neurons. Reactive astrocytes appeared to similar extents in the two genotypes, but they accumulated in the wounded area to a lesser extent in the deficient mice. Consequently, the deficient mice exhibited a marked reduction of scarring and enhanced neuronal regeneration after brain injury. These findings highlight the indispensable role of GlcNAc6ST-1 in brain KS biosynthesis and glial scar formation after brain injury.
Key words: axon regeneration / glial scar / keratan sulfate / N-acetylglucosamine 6-O-sulfotransferase / reactive astrocytes