The transcriptional response of cortical neurons to concussion reveals divergent fates after injury

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 and Claire E. Le Pichon (claire.lepichon@nih.gov)
Additional contact information
Mor R. Alkaslasi: National Institutes of Health
Eliza Y. H. Lloyd: National Institutes of Health
Austin S. Gable: National Institutes of Health
Hanna Silberberg: National Institutes of Health
Hector E. Yarur: National Institutes of Health
Valerie S. Tsai: National Institutes of Health
Mira Sohn: National Institutes of Health
Gennady Margolin: National Institutes of Health
Hugo A. Tejeda: National Institutes of Health
Claire E. Le Pichon: National Institutes of Health

Nature Communications, 2025, vol. 16, issue 1, 1-16

Abstract: 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.

Date: 2025
References: View references in EconPapers View complete reference list from CitEc
Citations:

Downloads: (external link)
https://www.nature.com/articles/s41467-025-56292-0 Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:16:y:2025:i:1:d:10.1038_s41467-025-56292-0

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/s41467-025-56292-0

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla (sonal.shukla@springer.com) and Springer Nature Abstracting and Indexing (indexing@springernature.com).