A research group including Assistant Professor Koji Sekiguchi and Specially Appointed Professor Daisuke Ito of the Department of Internal Medicine (Neurology) at the Keio University School of Medicine has clarified that the protein Iba1 (a calcium-binding protein), which is widely expressed in microglia, plays a crucial role in synaptic reorganization around damaged neurons and the survival of motor neurons, using an axonal injury model induced by facial nerve transection. This achievement is expected to be applied to the development of new treatments for neurological diseases. The results were published in the May 6 issue of the Journal of Neuroinflammation.
Provided by Keio University
Microglia are immune cells that quickly respond to nerve damage, accumulating at the affected site to protect the brain. In facial nerve transection models, they gather around the cell bodies of damaged motor neurons and perform a phenomenon called "synapse stripping," where they strip away and reorganize synapses. However, the role of microglia in this process remained unknown.
Therefore, the research group analyzed the responses of microglia and motor neurons in the facial nucleus after axonal injury caused by nerve transection, using wild-type mice and mutant mice deficient in Iba1, which is widely expressed in microglia.
The results revealed that in Iba1-deficient mice, the wrapping and contact of motor neurons by microglia after injury were reduced, and the synaptic reorganization observed in wild-type mice became insufficient. In the later stages, a decrease in the survival rate of motor neurons and an increase in DNA damage responses were observed. Furthermore, while the gene expression of microglia and motor neurons changed after axonal injury in wild-type mice, abnormalities were observed under Iba1 deficiency in both the state of injury-responsive microglia and the transcriptional response on the motor neuron side.
This study demonstrated that Iba1 is not merely a histological marker, but a functional molecule involved in synaptic reorganization and neuronal survival after axonal injury. In Alzheimer's disease, Iba1-positive microglia are known to play a crucial role in disease progression.
Ito stated, "While microglia are the most active 'moving' cells in the brain, reacting quickly to changes, they are also complex cells with diverse functions. In recent years, it has become clear that they express many genes related to Alzheimer's disease, drawing attention to them as therapeutic targets. We hope that research using this model mouse and Iba1 will contribute to clarifying the pathology and establishing treatments for many neurological diseases."
Journal Information
Publication: Journal of Neuroinflammation
Title: Iba1 deficiency impairs microglial synaptic remodeling and neuronal survival after axonal injury
DOI: 10.1186/s12974-026-03848-6
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