Developing and Characterizing a TDP-43 Drosophila Model of Frontotemporal Dementia

Abstract

Frontotemporal Dementia (FTD) is a progressive neurodegenerative disease that is characterized by intraneuronal protein aggregates. In 45% of FTD cases, these intracellular inclusions contain TAR-DNA binding protein (TDP-43). Though many animal models of FTD exist, none have been generated in Drosophila melanogaster through TDP-43 overexpression that recapitulate learning and memory deficits found in late stages of the disease. In an attempt to develop such a model, we overexpressed TDP-43 and disease-associated mutant variants in the mushroom bodies of the fly. Their learning and memory was tested using a courtship assay that measures conditioned decreases in male courtship behavior after experience with an unreceptive female. Subsequent courtship behavior with a receptive female was also measured. TDP-43 expressing flies did not show significant differences from controls in their courtship behavior with the unreceptive female, but all genotypes and ages showed a reduction in courtship when paired with the receptive female. Differences in courtship behavior between flies that subsequently mated with the receptive female and those that did not were also found. This suggests that genetic background of the transgenic flies and the behavior of the receptive female have profound effects on the courtship behavior of male Drosophila.