Allatostatin receptors and stress resilience in honey bees – ASTRAPIS

We measure the impact of exposure to subethal doses of pesticide exposure on different behavioural and physiological parameters that are used as indicators of stress. We do this by using a comparative approach between different bee castes to determine whether the sensitivity to stress differs between castes.
Our strategy consists in producing genetic tools, and identifying molecular agents, that may help us to increase or decrease the response to stress. By doing so we expect to find experimental ways to improve resilience to the negative effect of pesticide exposure, as revealed by a lesser impact of such exposure onto the measured parameters..

We have shown that some of the molecular actors of the stress response are present in the brain, particularly in brain centers known to be important for learning. This is in keeping with our demonstration of an effect of stress on learning abilities, which are important for foraging.
We also find that sensitivity to pesticide exposure depends on age, but does no seem differ between castes. There is also a marked genetic variability among colonies that may affect how they respond to stress.
A major output is the obtention of the necessary tools for the next steps of the project. We now have a genetic tool allowing us to modify the efficacy of the stress response pathway. We have also identified three chemical agents that may activate or inhibit this pathway.

Our immediate prospect is, during the next steps of our project, to test for the efficiency of our genetic and molecular tools, in order to determine whether, as expected, they can modulate the negative impact of pesticide exposure.

No published article or patent directly derived from the project so far.

Under selective pressure, many organisms have developed physiological mechanisms allowing them to avoid, and to cope with stress factors. Studying such mechanisms (stress responses) provides a way to understand adaptive mechanisms, as well as an opportunity to use these mechanisms in order to improve resilience. Still, in a rapidly evolving environment under the influence of human activity, animals encounter increasingly diverse sources of stress, with an increasing frequency. In such conditions, the selected stress responses may not be fully adapted, as suggested by the recent decline of honey bee populations. Given their high ecological and economical importance, many studies have helped to identify multiple factors with proved or potential impact on the fitness of colonies and individuals, and have pointed at synergistic effects of natural parasites, xenobiotics, and the impact of intensive agricultural practices on the diversity and quality of food sources. Given such diversity of negative factors, we claim that focus should be put on physiological processes involved in general stress responses rather than specific defence mechanisms, in order to understand - and possibly improve – stress resilience.
Recently, we have unravelled a new role for allatostatins in stress responses of the adult honey bee. These peptides, which can act as neurohormones, target many insects tissues involved in adapted responses to many stressors (muscles, brain, digestive tract, fat body). Our unpublished data show that, in response to stress, they also downregulate juvenile hormones, a key regulator of many physiological and behavioural specificities of the foraging behaviour. Since foragers appear particularly vulnerable to environmental stressors, and as juvenile hormone is also an internal stress signal, we propose to launch a research programme aimed at understanding the role of allatostatins and their receptors in the control of stress resilience, particularly in foragers. To that end, we will examine their capacity to regulate many adaptive processes triggered by a variety of stressors, and test the hypothesis that increased expression levels or activation of allatostatin receptors would promote stress resilience.
For this purpose, we plan an integrated approach studying molecular, cellular, physiological and behavioural aspects of stress responses, and linking individual and collective adaptations in this social insect. First, we will assess the susceptibility of foragers to stress, then evaluate the natural variation in expression levels of allatostatin receptors between colonies and correlate it with parameters of the stress response. The causal link between activation of the allatostatin pathway and stress resilience will be addressed through two parallel strategies: genetic manipulation of receptor expression by RNAi treatment, and pharmacological treatments with agonists for which a screening will be performed previously. In all cases, we will measure responses to three stressors believed to be primary causes of bee losses: starvation, infection by Nosema ceranae and ingestion of common pesticides (deltamethrin and fipronil), as a way to account for the diversity of biotic and abiotic stress met by this species.
By doing so, we expect to provide a significant breakthrough in the assessment and improvement of general stress response, and thus resilience, of honey bees, which may serve as a starting point for future agronomic applications.