Department of Pharmaceutical Sciences, Leslie Dan Faculty of Pharmacy, University of Toronto, Toronto, Canada.
Department of Anatomy, Division of Basic Medicine, Tokai University School of Medicine, Kanagawa, 259-1193, Japan.
Sci Rep. 2018 Nov 9;8(1):16639. doi: 10.1038/s41598-018-35129-5.
Neonicotinoids have become the most widely used class of insecticides world-wide. Although numerous studies have documented neonicotinoid toxicity in bees and other insects, the effects of exposure during early development in mammals remain largely unexplored. We assessed the effects of the neonicotinoid imidacloprid (IMI) in adult male and female mice after in utero and early postnatal exposure. Pregnant mice were infused with IMI (0.5 mg/kg/day) from gestational day 4 to the end of nursing at postnatal day 21. The young adult offspring were studied in a series of biochemical and behavioral tests. To assess reproducibility, the behavioral analyses were conducted in three separate studies using multiple exposed litters. Exposure to IMI reduced fecundity, and in adult offspring, decreased body weight in male but not female pups. Offspring from IMI-treated mothers displayed lower triglycerides, elevated motor activity, enhanced social dominance, reduced depressive-like behavior, and a diminution in social aggression compared to vehicle treated controls. Low levels of IMI were detected in the brains and livers of the treated mothers, while trace levels were detected in some offspring. Our results demonstrate that transient exposure to a neonicotinoid over the early developmental period induces long-lasting changes in behavior and brain function in mice.
新烟碱类杀虫剂已成为全球使用最广泛的杀虫剂。尽管大量研究记录了新烟碱类杀虫剂对蜜蜂和其他昆虫的毒性,但在哺乳动物早期发育过程中暴露的影响在很大程度上仍未得到探索。我们评估了新烟碱类杀虫剂吡虫啉(IMI)在宫内和新生后早期暴露于成年雄性和雌性小鼠中的作用。从妊娠第 4 天到出生后第 21 天哺乳结束,给怀孕的老鼠输注 IMI(0.5mg/kg/天)。在一系列生化和行为测试中研究了成年幼鼠。为了评估重现性,使用多个暴露的窝进行了三次单独的行为分析研究。暴露于 IMI 降低了生育能力,并且在成年后代中,雄性而非雌性幼崽的体重下降。与载体处理的对照组相比,来自接受 IMI 治疗的母亲的后代的甘油三酯水平较低,运动活性增强,社会支配力增强,抑郁样行为减少,社会攻击性降低。在接受治疗的母亲的大脑和肝脏中检测到低水平的 IMI,而在一些后代中检测到痕量水平的 IMI。我们的研究结果表明,在早期发育阶段短暂接触新烟碱类杀虫剂会导致小鼠的行为和大脑功能产生持久变化。