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Updated: Jun 10, 2025
Intravital Imaging of Axonal Interactions with Microglia and Macrophages in a Mouse Dorsal Column Crush Injury
Published on: November 23, 2014
In vivo imaging in mouse spinal cord reveals that microglia prevent degeneration of injured axons
Wanjie Wu1, Yingzhu He1, Yujun Chen2
1Department of Electronic and Computer Engineering, The Hong Kong University of Science and Technology, Hong Kong, P. R. China.
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.
Insights
Microglia (immune cells in the brain) protect spinal cord axons from injury by wrapping them at Nodes of Ranvier. This neuroprotective interaction involves specific microglial receptors and ion channels.
Area of Science:
- Neuroscience
- Immunology
- Cell Biology
Background:
- Microglia are key immune cells in the central nervous system, crucial for neuronal regulation.
- The precise mechanisms of microglia-neuron interactions are not fully understood.
- Understanding these interactions is vital for neurodegenerative disease research.
Purpose of the Study:
- To investigate the direct interactions between microglia and myelinated axons at Nodes of Ranvier.
- To elucidate the role of microglia in acute axonal injury and degeneration.
- To identify molecular players involved in microglia-axon interactions following injury.
Main Methods:
- In vivo two-photon imaging in mouse spinal cord models.
- Axonal injury induction and observation of microglial responses.
- Pharmacological inhibition of specific ion channels and microglial receptors.
Main Results:
- Microglia form direct, scanning contacts with axons at Nodes of Ranvier.
- Upon axonal injury, microglia adopt a wrapping morphology around the nodes.
- This wrapping is dependent on microglial P2Y12 receptors and involves NaV and K2P channels.
- Inhibition of NaV channels slowed axonal degeneration.
Conclusions:
- Microglia exhibit a neuroprotective role in acute spinal cord axon injury.
- Microglia-axon interactions at Nodes of Ranvier are critical for preventing degeneration.
- P2Y12 receptors, NaV, and K2P channels are key mediators of this protective response.
