Functional study of the clock gene period in response to xenobiotics and silencing by RNAi in Apis mellifera: implications on circadian rhythms and behavior

Abstract

The circadian clock plays essential roles in coordinating and synchronizing physiological and behavioral activities during the daily cycles and seasonal changes. It acts molecularly through the generation of circadian rhythms based on the cyclic expression of clock genes in an autoregulatory feedback loop. The current literature highlights how the knowledge about the molecular clock of organisms is essential to search for solutions to several problems, from pests and vectors control to treatment of diseases as cancer and Alzheimer. When compared with other organisms, social bees present a molecular clock that is more similar to mammals than to other insects. This observation makes them an ideal model to uncover the molecular pathways that govern the circadian rhythms together with mammals and permit to establish comparisons with other insects. Mammals and insects are regularly exposed to several xenobiotics and some of these compounds, found in drugs and pesticides, can affect the circadian rhythms negatively when used by inappropriate ways. The decline in bee populations, the primary pollinators, is linked frequently to the exposition of neurotoxic pesticides, which affect their physiology and behavior. Once the circadian rhythms are essential to the modulation of the adult development related to ageing and forage activity of worker bees, I hypothesize that the clock genes are potential targets that could be directly affected by pesticides. Thus, we propose two approaches to investigate the functional roles of the clock gene period (per) in physiology, behavior, and exposure to xenobiotics in the social bee Apis mellifera. First, we will perform a functional study of per through its knockdown in adult workers using RNAi to evaluate its effects on gene expression and cycling of other canonical clock genes and in the modulation of behavioral plasticity. Second, we will analyze how the exposure to imidacloprid, a neurotoxic compound that is present in a broad range of pesticides used in agriculture, could affect the transcriptional levels of clock genes, the circadian rhythms, survivor, and behavior of adult bees. We expect to contribute to knowledge about how the circadian rhythms regulate conserved pathways since they are critical elements to the biology of insects and mammals and also to uncover the link between circadian rhythms and metabolism of xenobiotics. (AU)