Date of Completion

2021

Document Type

Honors College Thesis

Department

Department of Biology

Thesis Type

College of Arts and Science Honors, Honors College

First Advisor

Jaeda Coutinho-Budd

Keywords

Alzheimers disease, glia, Draper, Drosophila, Mcr

Abstract

In mammals, microglia play the role of the resident macrophage in the central nervous system (CNS), whose duty is to engulf dead neurons, cellular debris, aging synapses and excess synaptic connections during development (Stevens et al., 2007). In Drosophila (fruit flies), cortex glia are a glial subset that play an analogous role to microglia. Draper, an engulfment receptor highly expressed within glia, has been identified as a principal player in engulfment (Freeman et al., 2003). However, the upstream activator of Draper in the Drosophila CNS remains ambiguous. This study explores the role of Macroglobulin complement protein (Mcr), a potential upstream activator of Draper, which is necessary for the engulfment of cellular debris and dead neurons (MacDonald et al., 2006, Ray et al., 2017, McLaughlin et al. 2019). Glial morphology and cross-talk with neurons, along with glial engulfment and regulation of Aβ plaques in the context of Alzheimer’s Disease (AD), is woefully understudied. This project aimed to further elucidate the extent of this communication within normal and Aβ42-expressing Drosophila. Given the recent identification of the role of p38 kinases in multiple sclerosis, another glial-based neurodegenerative disease (Krementsov et al., 2014), the role of p38 kinases in AD is explored through elimination of their glial expression in an Aβ42 background. Preliminary findings suggest that Mcr regulates engulfment through the Draper receptor in a cortex glia-specific fashion, and p38a contributes to the pathological phenotype observed in AD.

Creative Commons License

Creative Commons Attribution-Noncommercial-No Derivative Works 3.0 License
This work is licensed under a Creative Commons Attribution-Noncommercial-No Derivative Works 3.0 License.

Available for download on Friday, May 20, 2022

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