Sex-specific behavioral effects of acute exposure to the neonicotinoid clothianidin in mice
Sex-specific behavioral effects of acute exposure to the neonicotinoid clothianidin in mice
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DOI：
10.1016/j.taap.2022.116283
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发表时间：
2022-10-19
影响因子：
3.8
通讯作者：
Hoshi, Nobuhiko
中科院分区：
文献类型：
--
作者：
Kubo, Shizuka;Hirano, Tetsushi;Hoshi, Nobuhiko
虽然类烟碱是影响哺乳动物神经系统的主要杀虫剂类别之一，但对其影响的性别差异知之甚少。本研究的目的是检查是否神经行为的影响，类烟碱，噻虫胺（CLO），性别之间的差异。雄性和雌性C57 BL/6 N小鼠口服CLO（5或50 mg/kg）或低于慢性无明显不良作用水平（NOAEL），并进行情绪和学习功能的行为测试。在几个脑区的神经活动的变化和CLO及其代谢产物在血液和尿液中的浓度进行了测量。急性CLO暴露引起的性相关的行为影响，减少运动活动和升高的焦虑样行为在男性比女性更明显。此外，在新的识别测试和巴恩斯迷宫测试中均观察到CLO暴露对短期和长期学习记忆的男性特异性损害。在丘脑室旁核和海马齿状回中，c-fos阳性细胞数量呈显著性增加，分别与应激反应和学习功能有关。雄性动物血液和尿液中CLO和大多数代谢产物的浓度较高。这些结果支持了雄性小鼠比雌性小鼠更容易受到CLO神经行为影响的观点，并为类烟碱类化合物在哺乳动物神经功能中的风险评估提供了新的见解。
Although neonicotinoids are among the major classes of pesticides that affect mammalian nervous systems, little is known about sex differences in their effects. This study aimed to examine whether the neurobehavioral effects of a neonicotinoid, clothianidin (CLO), differed between sexes. Male and female C57BL/6N mice were orally administered CLO (5 or 50 mg/kg) at or below the chronic no-observed-adverse-effect-level (NOAEL) and subjected to behavioral tests of emotional and learning functions. Changes in neuroactivity in several brain regions and the concentrations of CLO and its metabolites in blood and urine were measured. Acute CLO exposure caused sex-related behavioral effects; decreases in locomotor activities and elevation of anxiety-like behaviors were more apparent in males than in females. In addition, male-specific impairment of short- and long-term learning memory by CLO exposure was observed in both the novel recognition test and the Barnes maze test. Maledominant increases in the number of c-fos positive cells were observed in the paraventricular thalamic nucleus in the thalamus and in the dentate gyrus in the hippocampus, which are related to the stress response and learning function, respectively. The concentrations of CLO and most metabolites in blood and urine were higher in males. These results support the notion that male mice are more vulnerable than females to the neurobehavioral effects of CLO and provide novel insights into the risk assessment of neonicotinoids in mammalian neuronal function.