Ganglioside GT1b prevents selective spinal synapse removal following peripheral nerve injury.

IF 6.5 1区生物学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY

EMBO Reports Pub Date : 2025-04-30 DOI:10.1038/s44319-025-00452-2

Jaesung Lee, Kyungchul Noh, Subeen Lee, Kwang Hwan Kim, Seohyun Chung, Hyoungsub Lim, Minkyu Hwang, Joon-Hyuk Lee, Won-Suk Chung, Sunghoe Chang, Sung Joong Lee

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Abstract

After peripheral nerve injury, the structure of the spinal cord is actively regulated by glial cells, contributing to the chronicity of neuropathic pain. However, the mechanism by which peripheral nerve injury leads to synaptic imbalance remains elusive. Here, we use a pH-reporter system and find that nerve injury triggers a reorganization of excitatory synapses that is influenced by the accumulation of the ganglioside GT1b at afferent terminals. GT1b acts as a protective signal against nerve injury-induced spinal synapse elimination. Inhibition of GT1b-synthesis increases glial phagocytosis of excitatory pre-synapses and reduces excitatory synapses post-injury. In vitro analyses reveal a positive correlation between GT1b accumulation and the frequency of pre-synaptic calcium activity, with GT1b-mediated suppression of glial phagocytosis occurring through SYK dephosphorylation. Our study highlights GT1b's pivotal role in preventing synapse elimination after nerve injury and offers new insight into the molecular underpinning of activity-dependent synaptic stability and glial phagocytosis.

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神经节苷脂GT1b防止周围神经损伤后选择性脊髓突触移除。

周围神经损伤后，脊髓结构受到神经胶质细胞的积极调控，导致神经性疼痛的慢性发生。然而，周围神经损伤导致突触失衡的机制尚不清楚。在这里，我们使用ph报告系统，发现神经损伤触发兴奋性突触的重组，这受传入末端神经节苷脂GT1b积累的影响。GT1b作为一种保护信号，防止神经损伤引起的脊髓突触消除。抑制gt1b合成可增加兴奋性突触前的胶质吞噬，并减少损伤后的兴奋性突触。体外分析显示，GT1b的积累与突触前钙活性频率呈正相关，GT1b介导的胶质吞噬抑制是通过SYK去磷酸化发生的。我们的研究强调了GT1b在防止神经损伤后突触消除中的关键作用，并为活动依赖性突触稳定性和胶质吞噬的分子基础提供了新的见解。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

EMBO Reports 生物-生化与分子生物学

CiteScore

11.20

自引率

1.30%

发文量

267

审稿时长

1 months

期刊介绍： EMBO Reports is a scientific journal that specializes in publishing research articles in the fields of molecular biology, cell biology, and developmental biology. The journal is known for its commitment to publishing high-quality, impactful research that provides novel physiological and functional insights. These insights are expected to be supported by robust evidence, with independent lines of inquiry validating the findings. The journal's scope includes both long and short-format papers, catering to different types of research contributions. It values studies that: Communicate major findings: Articles that report significant discoveries or advancements in the understanding of biological processes at the molecular, cellular, and developmental levels. Confirm important findings: Research that validates or supports existing knowledge in the field, reinforcing the reliability of previous studies. Refute prominent claims: Studies that challenge or disprove widely accepted ideas or hypotheses in the biosciences, contributing to the correction and evolution of scientific understanding. Present null data: Papers that report negative results or findings that do not support a particular hypothesis, which are crucial for the scientific process as they help to refine or redirect research efforts. EMBO Reports is dedicated to maintaining high standards of scientific rigor and integrity, ensuring that the research it publishes contributes meaningfully to the advancement of knowledge in the life sciences. By covering a broad spectrum of topics and encouraging the publication of both positive and negative results, the journal plays a vital role in promoting a comprehensive and balanced view of scientific inquiry.