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Title: The Effects of LPS Exposure on the Dynamic Function of Microglia in a Developing Zebrafish

Name: Michell Bilotti

Major: Biochemistry

School affiliation: School of Environmental and Biological Sciences

Programs: Aresty – Research or Conference Funding Recipient

Other contributors: Victoria DiBona, Cassandra Winz, Savannah Dziepak, Keith Cooper, Lori White

Abstract: Our lab utilizes Danio rerio (zebrafish) as a versatile and robust model organism for studying microglia-neuron interactions in the CNS. Microglia, the resident immune cells of the brain, have a distinct spectrum of morphologies that correlate to their main functions. Alterations in immune-neuron interactions, such as the overactivity of microglia, during development and throughout life are suggested to play a role in many neurodevelopmental and neurodegenerative disorders. We utilize transgenic lines with microglia expressing RFP and neurons expressing GFP to live confocal image fry following exposure to lipopolysaccharide (LPS), a known microglia activator. Our initial findings uncovered a dose-dependent activation of microglia morphology following early embryo treatment with LPS. Here, we expanded our studies to evaluate for dynamic changes in a key function of microglia, the surveillance of the neural network by processes. We captured a time-lapse Z-stack of individual RFP expressing microglia cells in contact with GFP expressing neurons by live in vivo imaging of LPS exposure zebrafish fry. We will quantify the amount of processes movement, hoping to prove statistical significance in increased movement signifying heightened dynamic motility. These studies will further establish our zebrafish model and techniques as a rapid-throughput system to improve the current toxicological standard assessment of lethality, sub-lethality, and physical abnormalities to include evaluation of cellular modifications, to more strictly define toxic levels following chemical exposures.