1. Academic Validation
  2. Ganglioside GT1b prevents selective spinal synapse removal following peripheral nerve injury

Ganglioside GT1b prevents selective spinal synapse removal following peripheral nerve injury

  • EMBO Rep. 2025 Jun;26(12):2994-3023. doi: 10.1038/s44319-025-00452-2.
Jaesung Lee 1 2 Kyungchul Noh 1 Subeen Lee 3 Kwang Hwan Kim 4 Seohyun Chung 1 Hyoungsub Lim 1 Minkyu Hwang 4 Joon-Hyuk Lee 5 Won-Suk Chung 5 Sunghoe Chang 6 Sung Joong Lee 7 8 9
Affiliations

Affiliations

  • 1 Department of Neuroscience and Physiology, Dental Research Institute, School of Dentistry, Seoul National University, Seoul, 08826, Republic of Korea.
  • 2 Department of Physiology and Biomedical Sciences, Dementia Research Center, College of Medicine, Seoul National University, Seoul, 08226, Republic of Korea.
  • 3 Interdisciplinary Program in Neuroscience, College of Natural Science, Seoul National University, Seoul, 08826, Republic of Korea.
  • 4 Department of Brain and Cognitive Sciences, College of Natural Sciences, Seoul National University, Seoul, 08826, Republic of Korea.
  • 5 Department of Biological Sciences, Korea Advanced Institute of Science and Technology, Daejeon, 34141, Republic of Korea.
  • 6 Department of Physiology and Biomedical Sciences, Dementia Research Center, College of Medicine, Seoul National University, Seoul, 08226, Republic of Korea. sunghoe@snu.ac.kr.
  • 7 Department of Neuroscience and Physiology, Dental Research Institute, School of Dentistry, Seoul National University, Seoul, 08826, Republic of Korea. sjlee87@snu.ac.kr.
  • 8 Interdisciplinary Program in Neuroscience, College of Natural Science, Seoul National University, Seoul, 08826, Republic of Korea. sjlee87@snu.ac.kr.
  • 9 Department of Brain and Cognitive Sciences, College of Natural Sciences, Seoul National University, Seoul, 08826, Republic of Korea. sjlee87@snu.ac.kr.
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.

Keywords

Astrocyte; GT1b; Microglia; Neuropathic Pain; Synapse Phagocytosis.

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