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Article Abstract

Spinal cord injury (SCI) damages neural circuits and triggers pro-inflammatory responses, resulting in locomotor impairment. The carbohydrate sulfotransferases GlcNAc6ST1 and GlcNAc6ST4 modulate the function of blood monocytes and microglia. However, their specific roles and enzymatic relationships in neuroinflammation and functional recovery after SCI remain unclear. In this study, we demonstrate that mice deficient in both GlcNAc6ST1 and GlcNAc6ST4 (DKO) exhibit improved locomotor recovery compared with mice with a single deficiency. DKO mice exhibit reduced levels of monocytes and activated macrophages/microglia at the injury site alongside increased serotonergic neural fibers, indicating enhanced neural plasticity. RNA sequencing reveals down-regulation of collagen I genes and up-regulation of genes encoding synaptic membrane components in the injured DKO spinal cord. In addition, GALAXY glycomic analysis shows an absence of GlcNAc-6-sulfated -glycans in the DKO spinal cord. These results suggest that GlcNAc6ST1 and GlcNAc6ST4 play complementary roles in promoting detrimental inflammatory responses post-SCI. Targeting these sulfotransferases could offer a novel therapeutic strategy to improve locomotor recovery after SCI.

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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC12394907PMC
http://dx.doi.org/10.26508/lsa.202503469DOI Listing

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Spinal cord injury (SCI) damages neural circuits and triggers pro-inflammatory responses, resulting in locomotor impairment. The carbohydrate sulfotransferases GlcNAc6ST1 and GlcNAc6ST4 modulate the function of blood monocytes and microglia. However, their specific roles and enzymatic relationships in neuroinflammation and functional recovery after SCI remain unclear.

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Complementary Role of GlcNAc6ST2 and GlcNAc6ST3 in Synthesis of CL40-Reactive Sialylated and Sulfated Glycans in the Mouse Pleural Mesothelium.

Molecules

July 2022

Unité de Glycobiologie Structurale et Fonctionnelle, UMR 8576 of the Centre National de la Recherche Scientifique, University of Lille, Villeneuve d'Ascq, F-59655 Lille, France.

Article Synopsis
  • Sialyl 6-sulfo Lewis X (6-sulfo sLe) and its derivative are important glycans found in high endothelial venules of lymphoid organs, with implications in allergic and asthmatic lung conditions.
  • The CL40 antibody identifies specific glycan structures that require both sialylation and GlcNAc-6-sulfation, revealing their presence in normal mouse lung tissues.
  • GlcNAc6ST2 and GlcNAc6ST3 are crucial for the production of CL40-positive glycans in the lung mesothelium, and their combined expression is necessary for proper in vivo glycan manifestation.
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Sulfation at the 6-O position of N-acetylglucosamine (GlcNAc) in the context of sialyl 6-sulfo Lewis x occurs constitutively on specific glycoproteins present on high-walled endothelial venules (HEV) and is important for L-selectin dependent homing of lymphocytes. Here, the proinflammatory cytokine, TNF-alpha, induced the expression of 6-sulfo N-acetyllactosamine (LacNAc)/Lewis x on human peripheral blood monocytes (PBM). This epitope was detected by monoclonal antibody (mAb) AG107 after neuraminidase treatment suggesting a sialylated epitope, which was present on the cell adhesion molecule, CD44.

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