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Age and Diet Affect Genetically Separable Secondary Injuries that Cause Acute Mortality Following Traumatic Brain Injury in Drosophila
- Source :
- G3: Genes, Genomes, Genetics, Vol 6, Iss 12, Pp 4151-4166 (2016), G3: Genes|Genomes|Genetics
- Publication Year :
- 2016
- Publisher :
- Oxford University Press, 2016.
-
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.
- Subjects :
- 0301 basic medicine
Male
hyperglycemia innate immune response
repetitive TBI
Time Factors
Transcription, Genetic
Traumatic brain injury
Mrna expression
Period (gene)
Physiology
Biology
Investigations
QH426-470
Affect (psychology)
Animals, Genetically Modified
03 medical and health sciences
Brain Injuries, Traumatic
medicine
Genetics
Animals
Genetic Predisposition to Disease
Mortality
Molecular Biology
Genetics (clinical)
2. Zero hunger
Innate immune system
Age Factors
Drosophila Genetic Reference Panel
medicine.disease
Immunity, Innate
Diet
Disease Models, Animal
030104 developmental biology
Gene Expression Regulation
Immunology
gene expression
Drosophila
Female
RNA-seq
Genetic Background
Subjects
Details
- Language :
- English
- ISSN :
- 21601836
- Volume :
- 6
- Issue :
- 12
- Database :
- OpenAIRE
- Journal :
- G3: Genes, Genomes, Genetics
- Accession number :
- edsair.doi.dedup.....f8274c7faf4480991abf49de81dcf2f2