Life science alliance · 2025
Enhanced locomotor recovery in mice lacking GlcNAc6ST1 and GlcNAc6ST4 following spinal cord injury.
СтатьяПоддержка исследования: вне правительства СШАНазвание и аннотация: Перевод пока не подготовлен
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Morozumi Masayoshi, Ozaki Tomoya, Nishitsuji Kazuchika, Takeda-Uchimura Yoshiko, Matsumoto Akiyuki, Ito Sadayuki, Imagama Shiro, Ishiguro Naoki, Yagi Hirokazu, Kato Koichi, Akama Tomoya O, Kosugi Tomoki, Maruyama Shoichi, Kadomatsu Kenji, Rosen Steven D, Noble-Haeusslein Linda J, Uchimura Kenji
Аннотация
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 N-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.