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Sex-specific regulation of microglial MyD88 in HMGB1-Induced anxiety phenotype in mice.

Publication ,  Journal Article
Rawls, A; Dziabis, J; Nguyen, D; Anbarci, D; Clark, M; Zhang, G; Dzirasa, K; Bilbo, SD
Published in: Neurobiol Stress
May 2025

Stress is a significant risk factor for the development and recurrence of anxiety disorders. Stress can profoundly impact the immune system, and lead to microglial functional alterations in the medial prefrontal cortex (mPFC), a brain region involved in the pathogenesis of anxiety. High mobility group box 1 protein (HMGB1) is a potent pro-inflammatory stimulus and danger-associated molecular pattern (DAMP) released from neuronal and non-neuronal cells following stress. HMGB1 provokes pro-inflammatory responses in the brain and, when administered locally, alters behavior in the absence of other stressors. In this study, we administered dsHMGB1 into the mPFC of male and female mice for 5 days to investigate the cellular and molecular mechanisms underlying HMGB1-induced behavioral dysfunction, with a focus on cell-type specificity and potential sex differences. Here, we demonstrate that dsHMGB1 infusion into the mPFC elicited behavior changes in both sexes but only altered microglial morphology robustly in female mice. Moreover, preventing microglial changes with cell-specific ablation of the MyD88 pathway prevented anxiety-like behaviors only in females. These results support the hypothesis that microglial MyD88 signaling is a critical mediator of HMGB1-induced stress responses, particularly in adult female mice.

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Published In

Neurobiol Stress

DOI

ISSN

2352-2895

Publication Date

May 2025

Volume

36

Start / End Page

100721

Location

United States

Related Subject Headings

  • 5204 Cognitive and computational psychology
  • 3209 Neurosciences
 

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Rawls, A., Dziabis, J., Nguyen, D., Anbarci, D., Clark, M., Zhang, G., … Bilbo, S. D. (2025). Sex-specific regulation of microglial MyD88 in HMGB1-Induced anxiety phenotype in mice. Neurobiol Stress, 36, 100721. https://doi.org/10.1016/j.ynstr.2025.100721
Rawls, Ashleigh, Julia Dziabis, Dang Nguyen, Dilara Anbarci, Madeline Clark, Grace Zhang, Kafui Dzirasa, and Staci D. Bilbo. “Sex-specific regulation of microglial MyD88 in HMGB1-Induced anxiety phenotype in mice.Neurobiol Stress 36 (May 2025): 100721. https://doi.org/10.1016/j.ynstr.2025.100721.
Rawls A, Dziabis J, Nguyen D, Anbarci D, Clark M, Zhang G, et al. Sex-specific regulation of microglial MyD88 in HMGB1-Induced anxiety phenotype in mice. Neurobiol Stress. 2025 May;36:100721.
Rawls, Ashleigh, et al. “Sex-specific regulation of microglial MyD88 in HMGB1-Induced anxiety phenotype in mice.Neurobiol Stress, vol. 36, May 2025, p. 100721. Pubmed, doi:10.1016/j.ynstr.2025.100721.
Rawls A, Dziabis J, Nguyen D, Anbarci D, Clark M, Zhang G, Dzirasa K, Bilbo SD. Sex-specific regulation of microglial MyD88 in HMGB1-Induced anxiety phenotype in mice. Neurobiol Stress. 2025 May;36:100721.
Journal cover image

Published In

Neurobiol Stress

DOI

ISSN

2352-2895

Publication Date

May 2025

Volume

36

Start / End Page

100721

Location

United States

Related Subject Headings

  • 5204 Cognitive and computational psychology
  • 3209 Neurosciences