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  4. N-Acetylglucosamine 6-O-Sulfotransferase-1-Deficient Mice Show Better Functional Recovery after Spinal Cord Injury

N-Acetylglucosamine 6-O-Sulfotransferase-1-Deficient Mice Show Better Functional Recovery after Spinal Cord Injury

The Journal of Neuroscience, 2010 · DOI: 10.1523/JNEUROSCI.2570-09.2010 · Published: April 28, 2010

Spinal Cord InjuryNeurologyGenetics

Simple Explanation

Neurons in the adult central nervous system (CNS) typically don't regenerate after injuries. This study investigates the role of keratan sulfate, a type of glycosaminoglycan, in functional recovery after spinal cord injury. The researchers used mice deficient in N-acetylglucosamine 6-O-sulfotransferase-1 (GlcNAc6ST-1), which lack a specific form of keratan sulfate. They found that these mice showed better motor function recovery after a spinal cord injury compared to normal mice. In vitro experiments showed that keratan sulfate proteoglycans are required for the inhibition of neurite outgrowth. This suggests that keratan sulfate plays a role in hindering nerve regeneration after injury.

Study Duration
8 Weeks
Participants
Adult C57BL/6J mice (female, 8 weeks old, 20–30 g)
Evidence Level
Level II: Animal Study

Key Findings

  • 1
    Mice lacking N-acetylglucosamine 6-O-sulfotransferase-1 (GlcNAc6ST-1), and thus deficient in keratan sulfate, exhibit significantly better motor function recovery after spinal cord injury, as measured by footfall tests, footprint tests, and Basso mouse scale locomotor scoring.
  • 2
    The GlcNAc6ST-1-deficient mice showed a restoration of neuromuscular system function below the lesion after electrical stimulation, indicating improved nerve function.
  • 3
    Axonal regrowth of both the corticospinal and raphespinal tracts was promoted in the GlcNAc6ST-1-deficient mice, suggesting enhanced nerve regeneration.

Research Summary

This study investigates the role of keratan sulfate (KS) in functional recovery after spinal cord injury (SCI) using N-acetylglucosamine 6-O-sulfotransferase-1 (GlcNAc6ST-1)-deficient mice, which lack 5D4-reactive KS in the CNS. The GlcNAc6ST-1-deficient mice showed better motor function recovery, restoration of neuromuscular function, and promoted axonal regrowth compared to wild-type mice after SCI. In vitro assays demonstrated that KS proteoglycans are required for proteoglycan-mediated inhibition of neurite outgrowth, suggesting KS expression is closely associated with functional disturbance after SCI.

Practical Implications

Therapeutic Target

Keratan sulfate may be a potential therapeutic target for improving functional recovery after spinal cord injury.

Animal Model

N-acetylglucosamine 6-O-sulfotransferase-1-deficient mice are a useful model to study the roles of keratan sulfate in the CNS.

Neurite Outgrowth Inhibition

Keratan sulfate is required for the proteoglycan-mediated inhibition of neurite outgrowth, suggesting a mechanism for its role in limiting nerve regeneration.

Study Limitations

  • 1
    The study was conducted on mice, and the results may not be directly applicable to humans.
  • 2
    The precise mechanisms by which keratan sulfate affects axonal regrowth and functional recovery require further investigation.
  • 3
    The role of other sulfation modifications mediated by GlcNAc6ST-1, besides keratan sulfate, cannot be completely excluded.

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