942B Poster - 15. Models of human disease
Friday April 08, 2:00 PM - 4:00 PM

Authors:
Eddie Cho ¹; Alec Candib ¹; Reina Hastings ¹; Gina Torabzadeh ¹; Jesse Rojas ¹; Sharon Zhang ¹; Marta Lipinski ²; Eric Ratliff ¹; Kim Finley ¹

Affiliations:
1) Shiley BioScience Center and Biology Dept, San Diego State University, San Diego, CA ; 2) Department of Anesthesiology, University of Maryland School of Medicine, Baltimore, MD

Keywords:
a. neural degeneration; f. autophagy

Traumatic brain injury (TBI) from accidents, domestic violence, sports and combat are a major cause of worldwide mortality and disability. Several groups have shown that adult Drosophila can be an effective model to examine the physiological, behavioral, neuronal, and molecular responses following TBI exposure. In this study, we have continued our Drosophila TBI research using RNA-sequencing to examine dynamic acute and long-term changes to central nervous system (CNS) gene expression profiles in adult flies following severe (sTBI) and mild repetitive TBI (mTBI) exposure. Principal component analysis (PCA) highlight highly dynamic transcriptional changes in male and female flies, with over a third of the Drosophila transcriptome showing 1.5-fold (+/-) alterations 4-hrs post-TBI. By 24-hrs, both genders rapidly shifted toward baseline transcriptome levels. 4-days post TBI male fly cohorts maintained a more baseline transcriptome profiles, while female flies had a second round of gene expression changes. Transcriptional changes trend toward baseline levels at 7-days post. Genes with significant alterations were analyzed using DAVID to identify functional gene-pathway clusters. At 4-hrs both genders had significant changes to NFKB and IMD pathway components, indicating rapid activation of stress and inflammatory signaling. At this time dramatic changes to neuronal/ERAD stress responses, ribosomal, vesical trafficking, and membrane transport components also occurred. At 24-hrs, inflammation remains elevated, along with alterations to cytoskeletal, kinase-phosphatase and proteolytic pathway members. At 4-days, there is a significant increase in select metallopeptidases as well as changes to organelle, protein and basement membrane modifying processes. 7-days post-TBI, DAVID revealed changes to alternative splicing factors, ER, cytochrome P450, glutathione metabolism, and members of the scavenger receptor pathways. Cell cycle components demonstrated multiplex differences, with PCNA and several cyclin genes increased significantly (4-hrs). Our novel trauma injury paradigm illustrates the effectiveness of model systems to identify conserved genetic factors influencing the complex stress and repair mechanisms underscoring in vivo trauma exposure. The goal of these findings is to identify genetic factors that are linked to adverse acute or protracted TBI outcomes and in the discovery of novel therapies for those experiencing trauma.