The transcriptional response of cortical neurons to concussion reveals divergent fates after injury
Abstract Traumatic brain injury (TBI) is a risk factor for neurodegeneration, however little is known about how this kind of injury alters neuron subtypes. In this study, we follow neuronal populations over time after a single mild TBI (mTBI) to assess long ranging consequences of injury at the leve...
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| Main Authors: | , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Nature Portfolio
2025-01-01
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| Series: | Nature Communications |
| Online Access: | https://doi.org/10.1038/s41467-025-56292-0 |
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| Summary: | Abstract Traumatic brain injury (TBI) is a risk factor for neurodegeneration, however little is known about how this kind of injury alters neuron subtypes. In this study, we follow neuronal populations over time after a single mild TBI (mTBI) to assess long ranging consequences of injury at the level of single, transcriptionally defined neuronal classes. We find that the stress-responsive Activating Transcription Factor 3 (ATF3) defines a population of cortical neurons after mTBI. Using an inducible reporter linked to ATF3, we genetically mark these damaged cells to track them over time. We find that a population in layer V undergoes cell death acutely after injury, while another in layer II/III survives long term and remains electrically active. To investigate the mechanism controlling layer V neuron death, we genetically silenced candidate stress response pathways. We found that the axon injury responsive dual leucine zipper kinase (DLK) is required for the layer V neuron death. This work provides a rationale for targeting the DLK signaling pathway as a therapeutic intervention for traumatic brain injury. Beyond this, our approach to track neurons after a mild, subclinical injury can inform our understanding of neuronal susceptibility to repeated impacts. |
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| ISSN: | 2041-1723 |