Contributions of age and sex in the emergence of neurodegenerative conditions following mild head trauma in Drosophila Melanogaster Restricted; Files & ToC

Abstract

Environmental insults, including those of physical nature, pose a significant risk for neurodegenerative disorders. Even seemingly innocuous hits to the head are believed to have long-lasting detrimental effects on brain function, which can emerge years after incident. However, it remains challenging to establish a causative connection between early-life exposure to mild head trauma and late-life emergence of neurodegenerative conditions. Furthermore, sex and age compound the outcome. Using our Drosophila head-impact model, we showed that early exposure to mild head trauma caused neurodegenerative conditions which only emerged in advanced ages and affected females disproportionately. Moreover, increasing age-at-injury further exacerbated the sexually dimorphic, late-life neurodegeneration. Next, we showed that mating is a primary cause for increased neurodegeneration in females. Specifically, Sex Peptide (SP) signaling in females was responsible for elevating vulnerability of the brain. Finally, RNA sequencing revealed a selected set of transcripts involved in the innate immune defense that were only altered in females. These transcriptomic changes exhibited a delayed onset and were only identified at chronic timepoints after injury in mated females, suggesting their role in the female-specific chronic responses to injury. Collectively, our findings established a causative link between early mild head trauma exposure and late-life neurodegeneration, affirmed the existence of sex differences in response to injury, and illuminated the critical contribution of age to the manifestation of neurodegenerative conditions. The identification of SP signaling in elevated female vulnerability also supports the emerging view that female reproductive processes may increase the risk for neurodegeneration.  

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School	Laney Graduate School
Department	Biological and Biomedical Sciences
Subfield / Discipline	Neuroscience
Degree	Ph.D.
Submission	Dissertation
Language	English
Research Field	Biology, Neuroscience
Keyword	Mild head injury Neurodegeneration Drosophila Sex differences
Committee Chair / Thesis Advisor	James Q. Zheng, Emory University
Committee Members	Shirley Zhang, Emory University Jie Jiang, Emory University Steven A. Sloan, Emory University Kenneth H. Moberg, Emory University Zhexing Wen, Emory University

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