Keratan sulfate restricts neural plasticity after spinal cord injury.

Abstract

Chondroitin sulfate (CS) proteoglycans are strong inhibitors of structural rearrangement after injuries of the adult CNS. In addition to CS chains, keratan sulfate (KS) chains are also covalently attached to some proteoglycans. CS and KS sometimes share the same core protein, but exist as independent sugar chains. However, the biological significance of KS remains elusive. Here, we addressed the question of whether KS is involved in plasticity after spinal cord injury. Keratanase II (K-II) specifically degraded KS, i.e., not CS, in vivo. This enzyme digestion promoted the recovery of motor and sensory function after spinal cord injury in rats. Consistent with this, axonal regeneration/sprouting was enhanced in K-II-treated rats. K-II and the CS-degrading enzyme chondroitinase ABC exerted comparable effects in vivo and in vitro. However, these two enzymes worked neither additively nor synergistically. These data and further in vitro studies involving artificial proteoglycans (KS/CS-albumin) and heat-denatured or reduced/alkylated proteoglycans suggested that all three components of the proteoglycan moiety, i.e., the core protein, CS chains, and KS chains, were required for the inhibitory activity of proteoglycans. We conclude that KS is essential for, and has an impact comparable to that of CS on, postinjury plasticity. Our study also established that KS and CS are independent requirements for the proteoglycan-mediated inhibition of axonal regeneration/sprouting.

• Authors: Shiro Imagama, Kazuma Sakamoto, Ryoji Tauchi, Ryuichi Shinjo, Tomohiro Ohgomori, Zenya Ito, Haoqian Zhang, Yoshihiro Nishida, Nagamasa Asami, Sawako Takeshita, Nobuo Sugiura, Hideto Watanabe, Toshihide Yamashita, Naoki Ishiguro, Yukihiro Matsuyama, Kenji Kadomatsu
• Journal: The Journal of neuroscience : the official journal of the Society for Neuroscience (J Neurosci) Vol. 31 Issue 47 Pg. 17091-102 (Nov 23 2011) ISSN: 1529-2401 [Electronic] United States
• PMID: 22114278 (Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Keratan Sulfate
• keratanase II
• Acetylglucosaminidase

Topics

• Acetylglucosaminidase (pharmacology)
• Animals
• Female
• Keratan Sulfate (physiology)
• Nerve Regeneration (drug effects, physiology)
• Neuronal Plasticity (drug effects, physiology)
• Rats
• Rats, Sprague-Dawley
• Recovery of Function (drug effects, physiology)
• Spinal Cord Injuries (metabolism)
• Thoracic Vertebrae