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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| Format: | Article |
| Language: | English |
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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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| author | Mor R. Alkaslasi Eliza Y. H. Lloyd Austin S. Gable Hanna Silberberg Hector E. Yarur Valerie S. Tsai Mira Sohn Gennady Margolin Hugo A. Tejeda Claire E. Le Pichon |
| author_facet | Mor R. Alkaslasi Eliza Y. H. Lloyd Austin S. Gable Hanna Silberberg Hector E. Yarur Valerie S. Tsai Mira Sohn Gennady Margolin Hugo A. Tejeda Claire E. Le Pichon |
| author_sort | Mor R. Alkaslasi |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-5c1cb7b7698241af86f5f571f25df6b4 |
| institution | Kabale University |
| issn | 2041-1723 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Nature Communications |
| spelling | doaj-art-5c1cb7b7698241af86f5f571f25df6b42025-02-02T12:32:48ZengNature PortfolioNature Communications2041-17232025-01-0116111610.1038/s41467-025-56292-0The transcriptional response of cortical neurons to concussion reveals divergent fates after injuryMor R. Alkaslasi0Eliza Y. H. Lloyd1Austin S. Gable2Hanna Silberberg3Hector E. Yarur4Valerie S. Tsai5Mira Sohn6Gennady Margolin7Hugo A. Tejeda8Claire E. Le Pichon9Unit on the Development of Neurodegeneration, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of HealthUnit on the Development of Neurodegeneration, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of HealthUnit on the Development of Neurodegeneration, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of HealthUnit on the Development of Neurodegeneration, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of HealthUnit on Neuromodulation and Synaptic Integration, National Institute of Mental Health, National Institutes of HealthUnit on Neuromodulation and Synaptic Integration, National Institute of Mental Health, National Institutes of HealthBioinformatics and Scientific Programming Core, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of HealthBioinformatics and Scientific Programming Core, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of HealthUnit on Neuromodulation and Synaptic Integration, National Institute of Mental Health, National Institutes of HealthUnit on the Development of Neurodegeneration, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of HealthAbstract 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.https://doi.org/10.1038/s41467-025-56292-0 |
| spellingShingle | Mor R. Alkaslasi Eliza Y. H. Lloyd Austin S. Gable Hanna Silberberg Hector E. Yarur Valerie S. Tsai Mira Sohn Gennady Margolin Hugo A. Tejeda Claire E. Le Pichon The transcriptional response of cortical neurons to concussion reveals divergent fates after injury Nature Communications |
| title | The transcriptional response of cortical neurons to concussion reveals divergent fates after injury |
| title_full | The transcriptional response of cortical neurons to concussion reveals divergent fates after injury |
| title_fullStr | The transcriptional response of cortical neurons to concussion reveals divergent fates after injury |
| title_full_unstemmed | The transcriptional response of cortical neurons to concussion reveals divergent fates after injury |
| title_short | The transcriptional response of cortical neurons to concussion reveals divergent fates after injury |
| title_sort | transcriptional response of cortical neurons to concussion reveals divergent fates after injury |
| url | https://doi.org/10.1038/s41467-025-56292-0 |
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