The Role of Tau Behind Mild Traumatic Brain Injury Induced Neurodegeneration in Drosophila melanogaster Restricted; Files Only

Abstract

Importance: Mild traumatic brain injury is one of the most prominent forms of head trauma and is a known risk for numerous neurodegenerative diseases. However, the mechanism through which early exposure to mild head trauma leads to later neurodegenerative conditions is yet to be understood.

Objective: To investigate the role of tau in the short- and long-term response to mild repetitive head trauma, such as the development of neurodegeneration.

Main Measures for Outcome: Lifelong Survivorship Monitoring, Negative Geotaxis Assay, Post-Mortem Brain Pathological Assay

Results: In the wild type (w1118) Drosophila, early onset mTBI led to later emergency of deficits and neurodegenerative conditions. Knocking out endogenous fly tau appears to have neuroprotective characteristics in female Drosophila against injury elicited cellular responses but led to adverse effects and deficits in male Drosophila. Knocking in human tau,Drosophila suffered from lifespan, climbing behavior, and pathological deficits. These deficits were observed in both males and females, while males exhibited more severe deficits.

Conclusion: Our data suggests that tau plays an important role in TBI-induced neurodegeneration, but this role may vary depending on sex. This sexual dimorphism manifests in the pathways associated with endogenous fly tau proteins and the processes involved in handling human tau proteins in Drosophila melanogaster. The dimorphism also becomes more pronounced following injury, exposing differences in mortality rates, behavior, and pathological impairments.

Table of Contents

Table of Contents

INTRODUCTION .........................................................................................................................................................1

METHODS ...................................................................................................................................................................4

RESULTS ......................................................................................................................................................................7

REPEATED MILD HEAD TRAUMA AFFECTS LIFESPAN................................................................................................. 7

MILD HEAD TRAUMA INDUCED ACUTE SENSORIMOTOR DEFICITS IN FEMALE W1118 FLIES BUT NOT MALE.............. 8

MILD HEAD TRAUMA INDUCED DEFICITS ARE MORE SEVERE IN MALE TAU KI FLIES THAN FEMALE ......................... 8

KNOCKING OUT DTAU RESULTED IN SEXUALLY DIMORPHIC RESULTS FOLLOWING MTBI......................................... 10

DISCUSSION ...............................................................................................................................................................12

FIGURES .....................................................................................................................................................................19

FIGURE 1: HEAD-FIRST INJURY APPARATUS............................................................................................................. 19

FIGURE 2: PRECISE HEAD-FIRST IMPACT................................................................................................................. 20

FIGURE 3: SURVIVORSHIP DATA.............................................................................................................................. 21

FIGURE 4: NEGATIVE GEOTAXIS ASSAY DATA OF W1118 FLIES ................................................................................. 22

FIGURE 5: NEGATIVE GEOTAXIS ASSAY DATA OF TAU KI FLIES ................................................................................ 23

FIGURE 6: NEGATIVE GEOTAXIS ASSAY DATA OF TAU KI/W1118 FLIES ..................................................................... 24

FIGURE 7: NEGATIVE GEOTAXIS ASSAY DATA OF TAU KO FLIES ............................................................................... 25

FIGURE 8: NEGATIVE GEOTAXIS ASSAY DATA OF TAU KO/W1118 FLIES .................................................................... 26

FIGURE 9: NEURODEGENERATIVE VACUOLE DATA OF W1118 FLIES ......................................................................... 27

FIGURE 10: NEURODEGENERATIVE VACUOLE DATA OF TAU KI FLIES ....................................................................... 28

FIGURE 11: NEURODEGENERATIVE VACUOLE DATA OF TAU KO FLIES ..................................................................... 29

REFERENCES ............................................................................................................................................................ 30

About this Honors Thesis

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School	Emory College
Department	Neuroscience and Behavioral Biology
Degree	B.S.
Submission	Honors Thesis
Language	English
Research Field	Biology, Cell Biology, Neuroscience
Palabra Clave	Drosophila Neurodegeneration mTBI
Committee Chair / Thesis Advisor	James Zheng, Emory University
Committee Members	Kenneth Moberg, Emory University Anita Devineni, Emory University

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