Glial immune-related pathways mediate effects of closed head traumatic brain injury on behavior and lethality in Drosophila

Bart van Alphen, Samuel Stewart, Marta Iwanaszko, Fangke Xu, Keyin Li, Sydney Rozenfeld, Anujaianthi Ramakrishnan, Taichi Q. Itoh, Shiju Sisobhan, Zuoheng Qin, Bridget C. Lear, Ravi Allada*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

Abstract

In traumatic brain injury (TBI), the initial injury phase is followed : by a secondary phase that contributes to neurodegeneration, yet the mechanisms leading to neuropathology in vivo remain to be elucidated. To address this question, we developed a Drosophila head-specific model for TBI termed Drosophila Closed Head Injury (dCHI), where well-controlled, nonpenetrating strikes are delivered to the head of unanesthetized flies. This assay recapitulates many TBI phenotypes, including increased mortality, impaired motor control, fragmented sleep, and increased neuronal cell death. TBI results in significant changes in the transcriptome, including up-regulation of genes encoding antimicrobial peptides (AMPs). To test the in vivo functional role of these changes, we examined TBI-dependent behavior and lethality in mutants of the master immune regulator NF-κB, important for AMP induction, and found that while sleep and motor function effects were reduced, lethality effects were enhanced. Similarly, loss of most AMP classes also renders flies susceptible to lethal TBI effects. These studies validate a new Drosophila TBI model and identify immune pathways as in vivo mediators of TBI effects.

Original languageEnglish (US)
Article numbere3001456
JournalPLoS biology
Volume20
Issue number1
DOIs
StatePublished - Jan 2022

ASJC Scopus subject areas

  • Neuroscience(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Immunology and Microbiology(all)
  • Agricultural and Biological Sciences(all)

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