Developing a Novel Drosophila Model of Frontotemporal Dementia (FTD) Based on TDP-43 Pathology

Abstract

The aim of my investigation is to develop a novel Drosophila melanogasterfly model of FTD by using both short-and long-term memory paradigms. I attempted to cause symptoms of FTD by overexpressing TDP-43 in the mushroom body neurons of the Drosophila flies. To investigate if the flies are showing memory deficits a behavioral oviposition assay was run that measured how many eggs female flies laid after 24 hour exposure to endoparasitic wasps. The control, Oregon-R, flies show a strong reduction in oviposition when compared to the TDP-43 flies. The flies overexpressing TDP-43wt show no reduction in oviposition while those overexpressing TDP-43G298S have a slight reduction in oviposition. The results gathered suggest that flies overexpressing TDP-43G298S in their mushroom body neurons may be showing symptoms of FTD but more trials need to be run in order to make any definite conclusions. Also, due to not seeing the wasp threat response in one control trial and both TDP-43wt trials more optimization needs to be done to ensure the initial results are true.