title: Using Drosophila as an integrated model to study mild repetitive traumatic brain injury.
abstract: Traumatic brain injury (TBI) is a major cause of morbidity and mortality worldwide. In addition, there has been a growing appreciation that even repetitive, milder forms of TBI (mTBI) can have long-term deleterious consequences to neural tissues. Hampering our understanding of genetic and environmental factors that influence the cellular and molecular responses to injury has been the limited availability of effective genetic model systems that could be used to identify the key genes and pathways that modulate both the acute and long-term responses to TBI. Here we report the development of a severe and mild-repetitive TBI model using Drosophila. Using this system, key features that are typically found in mammalian TBI models were also identified in flies, including the activation of inflammatory and autophagy responses, increased Tau phosphorylation and neuronal defects that impair sleep-related behaviors. This novel injury paradigm demonstrates the utility of Drosophila as an effective tool to validate genetic and environmental factors that influence the whole animal response to trauma and to identify prospective therapies needed for the treatment of TBI.
authors.affiliation: Donald P. Shiley BioScience Center, San Diego State University, San Diego, CA, USA.|Department of Biology, San Diego State University, San Diego, CA, USA.
authors.forename: Ayeh
authors.initials: A
authors.lastname: Barekat
authors.affiliation: Donald P. Shiley BioScience Center, San Diego State University, San Diego, CA, USA.
authors.forename: Arysa
authors.initials: A
authors.lastname: Gonzalez
authors.affiliation: Donald P. Shiley BioScience Center, San Diego State University, San Diego, CA, USA.
authors.forename: Ruth E
authors.initials: RE
authors.lastname: Mauntz
authors.affiliation: Donald P. Shiley BioScience Center, San Diego State University, San Diego, CA, USA.|Department of Biology, San Diego State University, San Diego, CA, USA.
authors.forename: Roxanne W
authors.initials: RW
authors.lastname: Kotzebue
authors.affiliation: Donald P. Shiley BioScience Center, San Diego State University, San Diego, CA, USA.|Department of Biology, San Diego State University, San Diego, CA, USA.
authors.forename: Brandon
authors.initials: B
authors.lastname: Molina
authors.affiliation: Donald P. Shiley BioScience Center, San Diego State University, San Diego, CA, USA.|Department of Biology, San Diego State University, San Diego, CA, USA.
authors.forename: Nadja
authors.initials: N
authors.lastname: El-Mecharrafie
authors.affiliation: Department of Biology, San Diego State University, San Diego, CA, USA.
authors.forename: Catherine J
authors.initials: CJ
authors.lastname: Conner
authors.affiliation: Department of Biology, San Diego State University, San Diego, CA, USA.
authors.forename: Shannon
authors.initials: S
authors.lastname: Garza
authors.affiliation: Department of Biology, San Diego State University, San Diego, CA, USA.
authors.forename: Girish C
authors.initials: GC
authors.lastname: Melkani
authors.affiliation: Department of Pharmacology, University of California San Diego, La Jolla, CA, USA.
authors.forename: William J
authors.initials: WJ
authors.lastname: Joiner
authors.affiliation: Shock, Trauma, and Anesthesiology Research (STAR) Center; Department of Anesthesiology, University of Maryland School of Medicine, Baltimore, MD, USA.
authors.forename: Marta M
authors.initials: MM
authors.lastname: Lipinski
authors.affiliation: Donald P. Shiley BioScience Center, San Diego State University, San Diego, CA, USA.|Department of Biology, San Diego State University, San Diego, CA, USA.|Department of Chemistry, San Diego State University, San Diego, CA, USA.
authors.forename: Kim D
authors.initials: KD
authors.lastname: Finley
authors.affiliation: Donald P. Shiley BioScience Center, San Diego State University, San Diego, CA, USA.|Department of Biology, San Diego State University, San Diego, CA, USA.|Department of Chemistry, San Diego State University, San Diego, CA, USA.
authors.forename: Eric P
authors.initials: EP
authors.lastname: Ratliff
mesh_terms: D000818:Animals; D000070642:Brain Injuries, Traumatic / Q000473:pathology* / Q000503:physiopathology*; D004195:Disease Models, Animal; D004330:Drosophila