Glial immune-related pathways as mediators of closed head TBI effects on behavior in Drosophila

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, which we ter...

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Published inbioRxiv
Main Authors Bart Van Alphen, Stewart, Samuel, Iwanaszko, Marta, Xu, Fangke, Bang, Eugenie, Rozenfeld, Sydney, Ramakrishnan, Anujaianthi, Itoh, Taichi Q, Braun, Rosemary I, Allada, Ravi
Format Paper
LanguageEnglish
Published Cold Spring Harbor Cold Spring Harbor Laboratory Press 20.09.2018
Subjects
Cell death
Gene expression
Head
Innate immunity
Insects
Lethality
Motor task performance
Neurodegeneration
Phenotypes
Purification
Ribonucleic acid
RNA
Sleep
Traumatic brain injury
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Summary: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, which we term Drosophila Closed Head Injury (dCHI), where well-controlled, non-penetrating strikes are directly 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. To discover novel mediators of TBI, we used glial targeted translating ribosome affinity purification in combination with RNA sequencing. We detected significant changes in the transcriptome at various times after TBI including in genes involved in innate immunity within 24 hours after TBI. 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- B and found that while lethality effects were still evident, changes in sleep and motor function were substantially reduced. These studies validate a new head-specific model for TBI in Drosophila and identify glial immune pathways as candidate in vivo mediators of TBI effects.
DOI:10.1101/422535