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  3. In vivo imaging in mouse spinal cord reveals that microglia prevent degeneration of injured axons

In vivo imaging in mouse spinal cord reveals that microglia prevent degeneration of injured axons

  • Nat Commun. 2024 Oct 13;15(1):8837. doi: 10.1038/s41467-024-53218-0.
Wanjie Wu # 1,  Yingzhu He # 1,  Yujun Chen # 2,  Yiming Fu 1,  Sicong He 3,  Kai Liu 4 5 6 7 8 9 10,  Jianan Y Qu 11 12 13
Affiliations

Affiliations

  • 1 Department of Electronic and Computer Engineering, The Hong Kong University of Science and Technology, Hong Kong, P. R. China.
  • 2 Division of Life Science, The Hong Kong University of Science and Technology, Hong Kong, P. R. China.
  • 3 Department of Immunology and Microbiology, School of Life Sciences, Southern University of Science and Technology, Shenzhen, China.
  • 4 Division of Life Science, The Hong Kong University of Science and Technology, Hong Kong, P. R. China. kailiu@ust.hk.
  • 5 Department of Chemical and Biological Engineering, The Hong Kong University of Science and Technology, Clear Water Bay, Kowloon, Hong Kong, Hong Kong, P. R. China. kailiu@ust.hk.
  • 6 StateKey Laboratory of Molecular Neuroscience, The Hong Kong University of Science and Technology, Hong Kong, P. R. China. kailiu@ust.hk.
  • 7 Biomedical Research Institute, Shenzhen Peking University-The Hong Kong University of Science and Technology Medical Center, Shenzhen, China. kailiu@ust.hk.
  • 8 Guangdong Provincial Key Laboratory of Brain Science, Disease and Drug Development, Shenzhen, Guangdong, China. kailiu@ust.hk.
  • 9 HKUST Shenzhen Research Institute, Guangdong, China. kailiu@ust.hk.
  • 10 Shenzhen-Hong Kong Institute of Brain Science, Guangdong, China. kailiu@ust.hk.
  • 11 Department of Electronic and Computer Engineering, The Hong Kong University of Science and Technology, Hong Kong, P. R. China. eequ@ust.hk.
  • 12 Department of Chemical and Biological Engineering, The Hong Kong University of Science and Technology, Clear Water Bay, Kowloon, Hong Kong, Hong Kong, P. R. China. eequ@ust.hk.
  • 13 Molecular Neuroscience Center, The Hong Kong University of Science and Technology, Hong Kong, P. R. China. eequ@ust.hk.
  • # Contributed equally.
PMID: 39397028 DOI: 10.1038/s41467-024-53218-0
Abstract

Microglia, the primary immune cells in the central nervous system, play a critical role in regulating neuronal function and fate through their interaction with neurons. Despite extensive research, the specific functions and mechanisms of microglia-neuron interactions remain incompletely understood. In this study, we demonstrate that microglia establish direct contact with myelinated axons at Nodes of Ranvier in the spinal cord of mice. The contact associated with neuronal activity occurs in a random scanning pattern. In response to axonal injury, microglia rapidly transform their contact into a robust wrapping form, preventing acute axonal degeneration from extending beyond the nodes. This wrapping behavior is dependent on the function of microglial P2Y12 receptors, which may be activated by ATP released through axonal volume-activated anion channels at the nodes. Additionally, voltage-gated sodium channels (NaV) and two-pore-domain potassium (K2P) channels contribute to the interaction between nodes and glial cells following injury, and inhibition of NaV delays axonal degeneration. Through in vivo imaging, our findings reveal a neuroprotective role of microglia during the acute phase of single spinal cord axon injury, achieved through neuron-glia interaction.

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