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Peer-reviewedCC BY-NCScience Advances

Differential sex-dependent responses of circulating steroid hormones and cortical gene expression in a traumatic brain injury model

  • Amberlyn Simmons1
  • Sierra F. Wilferd1
  • Sofia Campagnuolo1
  • Veronica Pena2
  • Heather Bimonte-Nelson2
  • Jason Newbern3
  • Rachael W. Sirianni1,4
  • Christopher L. Plaisier1,5
  • Sarah E. Stabenfeldt1,5
5 affiliations
  1. 1School of Biological and Health Systems Engineering, Arizona State University, Tempe, AZ, USA.
  2. 2Psychology, School of Life Sciences, Arizona State University, Tempe, AZ, USA.
  3. 3Neuroscience, School of Life Sciences, ASU, Tempe, AZ, USA.
  4. 4Department of Neurological Surgery, UMass Chan Medical School, Worcester, MA, USA.
  5. 5John Shufeldt School of Medicine and Medical Engineering, ASU, Tempe, AZ, USA.
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Abstract

Accumulating evidence supports sex differences in traumatic brain injury (TBI) outcomes. However, the underlying processes that lead to sex differences are not well understood. TBI results in the initiation of molecular and cellular responses that facilitate the progression of neurodegeneration. Little is known about how the circulating hormone profile is altered in response to TBI and whether sex differences in endocrine responses might shape secondary injury pathologies. Using intact male and female mice in a preclinical TBI model, we assessed changes in plasma hormone concentrations and cortical gene expression at 24 and 72 hours after TBI. We demonstrate that males and females exhibit sex-specific alterations in circulating levels of testosterone, androstenedione, estradiol, and dehydroepiandrosterone (DHEA) in response to TBI. We also identified sex differences in the expression of genes that are involved in immune responses and tissue remodeling after injury. Moreover, we report divergent circulating hormone and gene expression correlations between sexes.

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Cite

BibTeXRIS
BibTeX
@article{simmons2026differential,
  title = {{Differential sex-dependent responses of circulating steroid hormones and cortical gene expression in a traumatic brain injury model}},
  author = {Amberlyn Simmons and Sierra F. Wilferd and Sofia Campagnuolo and Veronica Pena and Heather Bimonte-Nelson and Jason Newbern and Rachael W. Sirianni and Christopher L. Plaisier and Sarah E. Stabenfeldt},
  journal = {Science Advances},
  year = {2026},
  month = oct,
  doi = {10.1126/sciadv.aei5171},
  url = {https://www.science.org/doi/10.1126/sciadv.aei5171},
  note = {CC BY-NC},
}
RIS
TY  - JOUR
TI  - Differential sex-dependent responses of circulating steroid hormones and cortical gene expression in a traumatic brain injury model
AU  - Amberlyn Simmons
AU  - Sierra F. Wilferd
AU  - Sofia Campagnuolo
AU  - Veronica Pena
AU  - Heather Bimonte-Nelson
AU  - Jason Newbern
AU  - Rachael W. Sirianni
AU  - Christopher L. Plaisier
AU  - Sarah E. Stabenfeldt
PY  - 2026
DA  - 2026/10/21
JO  - Science Advances
DO  - 10.1126/sciadv.aei5171
UR  - https://www.science.org/doi/10.1126/sciadv.aei5171
AB  - Accumulating evidence supports sex differences in traumatic brain injury (TBI) outcomes. However, the underlying processes that lead to sex differences are not well understood. TBI results in the initiation of molecular and cellular responses that facilitate the progression of neurodegeneration. Little is known about how the circulating hormone profile is altered in response to TBI and whether sex differences in endocrine responses might shape secondary injury pathologies. Using intact male and female mice in a preclinical TBI model, we assessed changes in plasma hormone concentrations and cortical gene expression at 24 and 72 hours after TBI. We demonstrate that males and females exhibit sex-specific alterations in circulating levels of testosterone, androstenedione, estradiol, and dehydroepiandrosterone (DHEA) in response to TBI. We also identified sex differences in the expression of genes that are involved in immune responses and tissue remodeling after injury. Moreover, we report divergent circulating hormone and gene expression correlations between sexes.
SN  - 2375-2548
ER  -