母亲孕期氰戊菊酯暴露，可能增加子代抑郁样行为的风险

Prenatal exposure to fenvalerate causes depressive-like behavior in adulthood by inhibiting brain-derived 5-HT synthesis

孕期氰戊菊酯暴露通过抑制脑源性5-HT合成诱发成年子代抑郁样行为

Author:Hui-Min Zhu, Bo Wang, Tao Wang, Jing Shao, Hui-Ru Chen, Chi Zhang, Li-Hua Xu, Jing-Jing Li, Min Wang, De-Xiang Xu, Xiu-Hong Meng

Source:Environ Pollut

Doi:10.1016/j.envpol.2024.124137

Abstract

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.

摘要

氰戊菊酯是一种典型的拟除虫菊酯类杀虫剂，其发育毒性已得到证实。本研究旨在探讨孕期氰戊菊酯暴露是否诱发子代成年期抑郁样行为。孕鼠于整个妊娠期每日经口灌胃玉米油或氰戊菊酯(2、20 mg/kg)。采用悬尾实验(tail suspension test, TST)、强迫游泳实验(forced swim test, FST)和蔗糖水偏好实验(sucrose preference test, SPT)评估抑郁样行为。结果表明，孕期暴露于氰戊菊酯的子代在TST和FST中的不动时间增加，糖偏好指数降低。孕期氰戊菊酯暴露的子代成年期前额叶中突触后膜标记物PSD95表达下调，并可追溯至妊娠第（GD）18天。相应地，氰戊菊酯处理组于GD18前额叶5-HT（突触发生的神经递质）水平降低，中脑5-HT合成关键酶——色氨酸羟化酶2 (TPH2)表达下调。此外，氰戊菊酯处理组子代中脑内质网应激相关蛋白GRP78和p-eIF2α表达上调。因此，本研究表明，孕期暴露于氰戊菊酯可能部分通过抑制脑源性5-HT合成诱发子代成年期抑郁样行为。