Abstract：
Clothianidin (CLO), a neonicotinoid that is widely used in forests and agricultural areas, was recently reported to cause toxicity in mammals. Although sensitivity to chemicals varies between sexes and developmental stages, studies that comprehensively evaluate both males and females are limited. Therefore, in this study we utilized murine models to compare the sex-specific differences in behavioral effects following CLO exposure at different developmental stages. We orally administered CLO to male and female mice as a single high-dose solution (80 mg/kg) during the postnatal period (2-week-old), adolescence (6-week-old), or maturity (10-week-old), and subsequently evaluated higher brain function. The behavioral battery test consisted of open field, light/dark transition, and contextual/cued fear conditioning tests conducted at three and seven months of age. After the behavioral test, the brains were dissected and prepared for immunohistochemical staining. We observed behavioral abnormalities in anxiety, spatial memory, and cued memory only in female mice. Moreover, the immunohistochemical analysis showed a reduction in astrocytes within the hippocampus of female mice with behavioral abnormalities. The behavioral abnormalities observed in female CLO-treated mice were consistent with the typical behavioral abnormalities associated with hippocampal astrocyte dysfunction. It is therefore possible that the CLO-induced behavioral abnormalities are at least in part related to a reduction in astrocyte numbers. The results of this study highlight the differences in behavioral effects following CLO exposure between sexes and developmental stages.
摘要：
噻虫胺(CLO)，一种新烟碱，广泛用于森林和农业地区，最近有报道对哺乳动物造成毒性。尽管对化学物质的敏感性因性别和发育阶段而异，全面评估男性和女性的研究是有限的。因此,在这项研究中，我们利用小鼠模型比较了不同发育阶段CLO暴露后行为效应的性别特异性差异。我们在出生后（2周龄）将CLO作为单个高剂量溶液（80mg/kg）口服给雄性和雌性小鼠，青春期（6周龄），或成熟度（10周龄），随后评估了更高的大脑功能。行为电池测试包括开放场地，亮/暗过渡，以及在三个月和七个月大时进行的上下文/提示恐惧条件测试。在行为测试之后,解剖大脑并准备免疫组织化学染色。我们观察到焦虑中的行为异常，空间记忆,只提示雌性老鼠的记忆。此外，免疫组织化学分析显示，行为异常的雌性小鼠海马内星形胶质细胞减少。在雌性CLO处理的小鼠中观察到的行为异常与与海马星形胶质细胞功能障碍相关的典型行为异常一致。因此，CLO诱导的行为异常可能至少部分与星形胶质细胞数量的减少有关。这项研究的结果突出了性别和发育阶段之间接触CLO后行为效应的差异。
