Death following traumatic brain injury in Drosophila is associated with intestinal barrier dysfunction.
Traumatic brain injury (TBI) is a major cause of death and disability worldwide. Unfavorable TBI outcomes result from primary mechanical injuries to the brain and ensuing secondary non-mechanical injuries that are not limited to the brain. Our genome-wide association study of Drosophila melanogaster revealed that the probability of death following TBI is associated with single nucleotide polymorphisms in genes involved in tissue barrier function and glucose homeostasis. We found that TBI causes intestinal and blood-brain barrier dysfunction and that intestinal barrier dysfunction is highly correlated with the probability of death. Furthermore, we found that ingestion of glucose after a primary injury increases the probability of death through a secondary injury mechanism that exacerbates intestinal barrier dysfunction. Our results indicate that natural variation in the probability of death following TBI is due in part to genetic differences that affect intestinal barrier dysfunction.
Department of Cell and Regenerative Biology, School of Medicine and Public Health, University of Wisconsin-Madison, Madison, United States.
Rebeccah J
RJ
Katzenberger
Laboratory of Genetics, University of Wisconsin-Madison, Madison, United States.
Stanislava
S
Chtarbanova
Department of Cell and Regenerative Biology, School of Medicine and Public Health, University of Wisconsin-Madison, Madison, United States.
Stacey A
SA
Rimkus
Department of Cell and Regenerative Biology, School of Medicine and Public Health, University of Wisconsin-Madison, Madison, United States.
Julie A
JA
Fischer
Department of Cell and Regenerative Biology, School of Medicine and Public Health, University of Wisconsin-Madison, Madison, United States.
Gulpreet
G
Kaur
Department of Cell and Regenerative Biology, School of Medicine and Public Health, University of Wisconsin-Madison, Madison, United States.
Jocelyn M
JM
Seppala
Department of Cell and Regenerative Biology, School of Medicine and Public Health, University of Wisconsin-Madison, Madison, United States.
Laura C
LC
Swanson
Department of Cell and Regenerative Biology, School of Medicine and Public Health, University of Wisconsin-Madison, Madison, United States.
Jocelyn E
JE
Zajac
Laboratory of Genetics, University of Wisconsin-Madison, Madison, United States.
Barry
B
Ganetzky
Department of Cell and Regenerative Biology, School of Medicine and Public Health, University of Wisconsin-Madison, Madison, United States.
David A
DA
Wassarman
D000818:Animals; D000831:Animals, Newborn; D058491:Bacterial Load; D018916:Blood-Aqueous Barrier / Q000378:metabolism / Q000503:physiopathology; D001812:Blood-Brain Barrier / Q000378:metabolism / Q000503:physiopathology; D001813:Blood-Retinal Barrier / Q000378:metabolism / Q000503:physiopathology; D001930:Brain Injuries / Q000235:genetics* / Q000378:metabolism / Q000401:mortality; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D004195:Disease Models, Animal; D029721:Drosophila Proteins / Q000235:genetics* / Q000378:metabolism; D004331:Drosophila melanogaster / Q000235:genetics / Q000378:metabolism; D015870:Gene Expression; D005947:Glucose / Q000008:administration & dosage / Q000378:metabolism / Q000494:pharmacology; D006458:Hemolymph / Q000378:metabolism / Q000382:microbiology; D006801:Humans; D007413:Intestinal Mucosa / Q000378:metabolism*; D007422:Intestines / Q000187:drug effects / Q000503:physiopathology; D020641:Polymorphism, Single Nucleotide; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012307:Risk Factors; D015996:Survival Rate; D013997:Time Factors; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism
D004268:DNA-Binding Proteins; D029721:Drosophila Proteins; D014157:Transcription Factors; C062330:grh protein, Drosophila; D005947:Glucose
D. melanogaster; blood–brain barrier; chromosomes; genes; glucose homeostasis; grainyhead; hexosamine biosynthesis pathway; innate immune response; neuroscience; septate junction