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Prenatal exposure to fenvalerate causes depressive-like behavior in adulthood by inhibiting brain-derived 5-HT synthesis
Environmental Pollution ( IF 7.6 ) Pub Date : 2024-05-11 , DOI: 10.1016/j.envpol.2024.124137
Hui-Min Zhu 1 , Bo Wang 1 , Tao Wang 1 , Jing Shao 2 , Hui-Ru Chen 2 , Chi Zhang 2 , Li-Hua Xu 2 , Jing-Jing Li 2 , Min Wang 2 , De-Xiang Xu 1 , Xiu-Hong Meng 1
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The developmental toxicity of fenvalerate, a representative pyrethroid insecticide, is well documented. The present study aimed to explore whether prenatal exposure to fenvalerate causes depression-like behavior in adulthood. Pregnant mice were orally administrated with either corn oil or fenvalerate (2 or 20 mg/kg) during pregnancy. Depressive-like behaviors were assessed by tail suspension test (TST), forced swim test (FST) and sucrose preference test (SPT). Immobility times in TST and FST were increased in offspring whose mothers were exposed to fenvalerate throughout pregnancy. By contrast, sugar preference index, as determined by SPT, was decreased in fenvalerate-exposed offspring. Prefrontal PSD95, a postsynaptic membrane marker, was downregulated in fenvalerate-exposed adulthood offspring. Fenvalerate-induced reduction of prefrontal PSD95 began at GD18 fetal period. Accordingly, prefrontal 5-HT, a neurotransmitter for synaptogenesis, was also reduced in fenvalerate-exposed GD18 fetuses. Tryptophan hydroxylase 2 (TPH2), a key enzyme for 5-HT synthesis, was downregulated in the midbrain of fenvalerate-exposed GD18 fetuses. Additional experiment showed that GRP78 and p-eIF2α, two endoplasmic reticulum stress-related proteins, were increased in the midbrain of fenvalerate-exposed fetal mice. The present results suggest that prenatal exposure to fenvalerate causes depressive-like behavior in adulthood, partially by inhibiting brain-derived 5-HT synthesis.

中文翻译:


产前接触氰戊菊酯会抑制脑源性 5-HT 合成,从而导致成年后出现抑郁样行为



具有代表性的拟除虫菊酯杀虫剂氰戊菊酯的发育毒性已有充分记录。本研究旨在探讨产前接触氰戊菊酯是否会导致成年后出现抑郁样行为。怀孕期间给怀孕小鼠口服玉米油或氰戊菊酯(2 或 20 mg/kg)。通过悬尾测试(TST)、强迫游泳测试(FST)和蔗糖偏好测试(SPT)评估抑郁样行为。母亲在整个怀孕期间接触氰戊菊酯的后代的 TST 和 FST 不动时间增加。相比之下,由 SPT 测定的糖偏好指数在暴露于氰戊菊酯的后代中有所下降。前额叶 PSD95(一种突触后膜标记物)在暴露于氰戊菊酯的成年后代中下调。氰戊菊酯诱导的前额叶 PSD95 降低始于 GD18 胎儿期。因此,在暴露于氰戊菊酯的 GD18 胎儿中,前额叶 5-HT(一种用于突触发生的神经递质)也减少了。色氨酸羟化酶 2 (TPH2) 是 5-HT 合成的关键酶,在接触氰戊菊酯的 GD18 胎儿中脑中表达下调。额外的实验表明,暴露于氰戊菊酯的胎鼠的中脑中,两种内质网应激相关蛋白 GRP78 和 p-eIF2α 增加。目前的结果表明,产前接触氰戊菊酯会导致成年后出现抑郁样行为,部分原因是抑制脑源性 5-HT 合成。
更新日期:2024-05-11
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