Hormesis in insects: clarifying the dose-response and implications for beneficial insects

虽然人们早就认识到，当以中等或高水平施用时，应激可能对生物体产生有害影响，但现在清楚的是，低水平的应激源，如毒物，实际上可以刺激生物过程。当给予高剂量的应激源时，生物效应受到抑制，而当生物体暴露于温和量的应激源时受到刺激，这种现象被称为“兴奋效应”。在我们对毒物兴奋效应现象的研究中，我们反复证明，对昆虫施用低剂量的杀虫剂可以急剧增加种群增长，增加后代的体重，并改变与应激反应和发育有关的基因的表达。然而，一些基本的和应用的问题仍然围绕着激效反应和昆虫的激素诱导的刺激。目前研究计划的主要长期目标是更好地了解农药诱导的昆虫兴奋效应的性质，并证明有益昆虫兴奋效应现象的发生和潜在应用。具体而言，多名高素质人员将进行实验，以检验假设，以确定：（1）农药诱导昆虫生殖兴奋效应的分子和生化机制;（2）兴奋前毒性的原因（即超敏反应）在昆虫接触低于刺激性的毒物中观察到（3）是否可以战略性地对有益的捕食性昆虫和寄生性昆虫施加适度的胁迫，以提高它们的生产力，用于生物防治;以及（4）暴露于低剂量农药是否能刺激蜜蜂的学习和繁殖。对兴奋效应的研究正在迅速增加，但我们对这种现象的基本理解仍然存在重要差距。拟议的研究计划将是高度原创性的，将具有高度的跨学科影响，融合了毒理学，昆虫分子生物学，风险评估，作物保护和生物控制研究人员感兴趣的问题。使用完善的昆虫杀虫剂模型，该研究将发现引起观察到的激素剂量反应的潜在分子和生物学机制。我们提出的对前激素毒性原因的调查是非常原始的，可以为该领域开辟道路。这项研究还将探讨适应性压力反应对生物适应性的影响，这是研究毒物兴奋效应的进化生物学家之间存在相当大争议的一个领域。同时，我们的研究对农业和害虫管理具有重要的实际意义。在农业方面，有报告指出农药会刺激昆虫种群的增长。由此产生的“虫害死灰复燃”不仅可能导致作物/商品损失增加，还可能导致额外的杀虫剂处理，从而可能加剧非目标影响、杀虫剂抗药性的发展和环境污染。因此，有经济和环境的激励，以更好地了解农药诱导的昆虫兴奋效应的发生和后果。另一方面，轻度胁迫在刺激有益昆虫（如传粉昆虫、天敌）发育方面的潜在意义在很大程度上被忽视了。作为我们的研究的结果，生物防治行业可以实现其大量饲养生产实践的显着效益。此外，暴露于低剂量农药的蜜蜂的兴奋（刺激）反应的证明将是真正的突破性的，应该让那些认为农药暴露总是对蜜蜂构成风险的人停下来。

Although it has long been appreciated that stress, when administered at moderate or high levels, can have deleterious effects on organisms, it is now clear that low levels of stressors, such as poisons, can actually stimulate biological processes. This phenomenon of inhibition of biological effects when a stressor is given at high doses, with stimulation when the organism is exposed to mild amounts of the stressor, is known as “hormesis”. In our studies on the hormesis phenomenon, we have repeatedly demonstrated that low doses of insecticide administered to insects can sharply increase population growth, increase weight of progeny, and alter expression of genes involved in stress responses and development. However, a number of basic and applied questions remain surrounding the hormetic response and insecticide-induced stimulations in insects. The principle long-term goals of the current research program are to better understand the nature of pesticide-induced hormesis in insects, and to demonstrate the occurrence and potential applications of the hormesis phenomenon for beneficial insects. Specifically, multiple highly qualified personnel will conduct experiments to test hypotheses to determine: (1) the molecular and biochemical mechanisms of pesticide-induced reproduction hormesis in insects; (2) the cause of pre-hormetic toxicity (i.e. hypersensitivity) observed in insects exposed to poisons below stimulatory (hormetic) concentrations; (3) whether mild levels of stress can be strategically applied to beneficial insect predators and parasitoids in order to boost their productivity for biological control; and (4) if exposure to low doses of pesticide can stimulate learning and reproduction in bees. The study of hormesis is rapidly increasing, but important gaps in our basic understanding of the phenomenon remain. The proposed research program will be highly original and will have high inter-disciplinary impact, melding questions of interest to researchers in toxicology, insect molecular biology, risk assessment, crop protection, and biological control. Using well-established insect-insecticide models, the research will discover the underlying molecular and biological mechanisms that give rise to observed hormetic dose-responses. Our proposed investigations into the causes of prehormetic toxicity are highly original and could be trailblazing for the field. The research will also probe questions surrounding the consequence of adaptive stress responses on biological fitness, an area of considerable debate among evolutionary biologists that study hormesis. At the same time, our research has important practical implications for agriculture and insect pest management. In agriculture, pesticide-induced stimulations of insect population growth have been reported. The resulting “pest resurgences” not only may result in increased crop/commodity damage, but may also lead to additional pesticide treatments, potentially exacerbating non-target impacts, insecticide resistance development, and environmental contamination. Thus, there are economic and environmental incentives to better understand the occurrence and consequences of pesticide-induced hormesis in insects. On the other hand, the potential implications of mild stress in stimulating development of beneficial insects (e.g. pollinators, natural enemies) have been largely ignored. As a consequence of our research, the biological control industry could realize significant benefits to its mass rearing production practices. Moreover, the demonstration of hormetic (stimulatory) responses in bees exposed to low doses of pesticide would be truly ground-breaking, and should give pause to those who assume that pesticide exposure always poses a risk to bees.