title: Age and Diet Affect Genetically Separable Secondary Injuries that Cause Acute Mortality Following Traumatic Brain Injury in Drosophila.
abstract: Outcomes of traumatic brain injury (TBI) vary because of differences in primary and secondary injuries. Primary injuries occur at the time of a traumatic event, whereas secondary injuries occur later as a result of cellular and molecular events activated in the brain and other tissues by primary injuries. We used a Drosophila melanogaster TBI model to investigate secondary injuries that cause acute mortality. By analyzing mortality percentage within 24 hr of primary injuries, we previously found that age at the time of primary injuries and diet afterward affect the severity of secondary injuries. Here, we show that secondary injuries peaked in activity 1-8 hr after primary injuries. Additionally, we demonstrate that age and diet activated distinct secondary injuries in a genotype-specific manner, and that concurrent activation of age- and diet-regulated secondary injuries synergistically increased mortality. To identify genes involved in secondary injuries that cause mortality, we compared genome-wide mRNA expression profiles of uninjured and injured flies under age and diet conditions that had different mortalities. During the peak period of secondary injuries, innate immune response genes were the predominant class of genes that changed expression. Furthermore, age and diet affected the magnitude of the change in expression of some innate immune response genes, suggesting roles for these genes in inhibiting secondary injuries that cause mortality. Our results indicate that the complexity of TBI outcomes is due in part to distinct, genetically controlled, age- and diet-regulated mechanisms that promote secondary injuries and that involve a subset of innate immune response genes.
authors.affiliation: Department of Medical Genetics, School of Medicine and Public Health, University of Wisconsin-Madison, Wisconsin 53706.
authors.forename: Rebeccah J
authors.initials: RJ
authors.lastname: Katzenberger
authors.affiliation: Department of Genetics, College of Agriculture and Life Sciences, University of Wisconsin-Madison, Wisconsin 53706 ganetzky@wisc.edu dawassarman@wisc.edu.
authors.forename: Barry
authors.initials: B
authors.lastname: Ganetzky
authors.affiliation: Department of Medical Genetics, School of Medicine and Public Health, University of Wisconsin-Madison, Wisconsin 53706 ganetzky@wisc.edu dawassarman@wisc.edu.
authors.forename: David A
authors.initials: DA
authors.lastname: Wassarman
mesh_terms: D000367:Age Factors; D000818:Animals; D030801:Animals, Genetically Modified; D000070642:Brain Injuries, Traumatic / Q000235:genetics* / Q000276:immunology / Q000401:mortality*; D004032:Diet; D004195:Disease Models, Animal; D004330:Drosophila; D005260:Female; D005786:Gene Expression Regulation; D000068617:Genetic Background; D020022:Genetic Predisposition to Disease; D007113:Immunity, Innate / Q000235:genetics; D008297:Male; D009026:Mortality; D013997:Time Factors; D014158:Transcription, Genetic
keywords: Drosophila Genetic Reference Panel; RNA-seq; gene expression; hyperglycemia innate immune response; repetitive TBI