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Updated: May 9, 2026
Intravital Imaging of Axonal Interactions with Microglia and Macrophages in a Mouse Dorsal Column Crush Injury
Published on: November 23, 2014
Iba1 deficiency impairs microglial synaptic remodeling and neuronal survival after axonal injury
Koji Sekiguchi1, Hirotaka Shoji2, Tomoko Shindo3
1Department of Neurology, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo, 160-8582, Japan.
Background:
Microglia remodel neuronal circuits in pathological conditions; however, the molecular requirements for these responses and their consequences for motoneuron survival remain unclear.
Methods:
Aif1 (Iba1) knockout mice were generated using CRISPR/Cas9-mediated deletion, and baseline phenotypes and responses to unilateral facial nerve axotomy were assessed using immunohistochemistry, transmission electron microscopy, and single-nucleus RNA sequencing of the facial motor nucleus. Motoneuron survival and nuclear γH2AX foci were evaluated 28 days post-axotomy.
Findings:
Under baseline conditions, Iba1-/- mice had reduced body weights and mild behavioral abnormalities compared to wild-type mice. After axotomy, microglial ensheathment of ChAT-positive facial motoneurons was reduced, with fewer neurons showing extensive perisomatic microglial coverage than in Iba1+/+ mice. Ultrastructurally, somatic synapse loss observed after injury in wild-type mice was not detected in Iba1-/- mice, and fewer injured motoneurons were in contact with microglial processes. Single-nucleus transcriptomics showed an exaggerated expansion of an interferon-responsive microglial state in Iba1-/- mice after axotomy, whereas injured motoneurons displayed altered transcriptional programs related to synapse organization and neurotransmission. At 28 days, Iba1-/- mice showed reduced motoneuron survival, lower ChAT expression, and increased nuclear γH2AX foci.
Interpretation:
Iba1 supports microglia-neuron cross-talk that enables effective perisomatic remodefling after axonal injury; disruption of this response is accompanied by inflammatory-state shifts and compromised motoneuron survival.
Insights
The protein Iba1 (allograft inflammatory factor 1) is crucial for microglia to support motoneuron survival after nerve injury. Disrupting Iba1 impairs this interaction, leading to inflammation and neuron death.
Area of Science:
- Neuroscience
- Immunology
- Cell Biology
Background:
- Microglia play a role in neuronal circuit remodeling during disease.
- The molecular mechanisms and impact on motoneuron survival are not fully understood.
Purpose of the Study:
- To investigate the role of Iba1 in microglial responses to facial nerve axotomy.
- To determine the consequences of Iba1 deficiency on motoneuron survival and circuit integrity.
Main Methods:
- Generated Iba1 knockout mice using CRISPR/Cas9.
- Assessed phenotypes via immunohistochemistry, electron microscopy, and single-nucleus RNA sequencing.
- Evaluated motoneuron survival and DNA damage 28 days post-axotomy.
Main Results:
- Iba1 knockout mice exhibited reduced body weight and mild behavioral deficits.
- Post-axotomy, Iba1 deficiency led to decreased microglial coverage of motoneurons and reduced synapse loss.
- Transcriptomics revealed an exaggerated interferon-responsive microglial state and altered motoneuron transcriptional programs in Iba1 knockout mice.
- Iba1 knockout mice showed reduced motoneuron survival, lower ChAT expression, and increased DNA damage.
Conclusions:
- Iba1 facilitates essential microglia-neuron communication for perisomatic remodeling after axonal injury.
- Disruption of Iba1-mediated responses results in detrimental inflammatory shifts and compromised motoneuron survival.
