Abstract
Neurodevelopmental disorders (NDDs) are a heterogeneous group of disorders caused by both genetic and environmental factors. Fragile X Mental Retardation 1 (FMR1) is an NDD-associated genetic factor that causes fragile X syndrome and is the most common single gene cause of autism spectrum disorder (ASD). Bisphenol A (BPA) is a high-volume chemical that is produced worldwide and used in the synthesis of polycarbonate plastics and epoxy resins. BPA has well established roles as an endocrine disrupting chemical (EDC) and emerging studies indicate that BPA may also impact neurodevelopment. The purpose of this study is to use the common fruit fly, Drosophila melanogaster, to determine how BPA impacts NDD-related phenotypes—including synapse formation, learning, and memory recall. These phenotypes were examined in two wild-type Drosophila strains (w1118 and Canton-S), as well as in fruit flies carrying a null mutation in dFmr1, the Drosophila ortholog of FMR1. Following BPA exposure, synapse formation at the larval neuromuscular junction (NMJ) of late third instar larvae was examined using confocal microscopy. Synaptic boutons and axonal branches were manually quantified. This approach revealed no significant difference in the number of synaptic boutons and axonal branches for wild-type larvae, but we observed an increase in the number of synaptic boutons in the dFmr1 mutant larvae exposed to BPA. Nonassociative learning and memory recall were measured using a predator-response experimental paradigm involving endoparasitoid wasps. Following BPA exposure, we measured the physiological response (rate of oviposition) and the substrate preference of the two wild-type strains and in dFmr1 mutant flies. Results from the rate of oviposition analysis indicate that BPA exposure impairs learning in both wild-type strains, but has no impact on dFmr1 mutant flies. Results from the substrate preference analysis indicate that BPA exposure impairs long-term nonassociative memory in w1118 flies but has no impact on this phenotype in Canton S or dFmr1 mutant flies.