Pubertal fenvalerate exposure impairs cognitive and behavioral development partially through down-regulating hippocampal thyroid hormone receptor signaling

Highlight：青春期低剂量氰戊菊酯暴露可能通过下调海马甲状腺激素信号损害小鼠认知和行为发育。本研究提示人们关注，发育关键期低剂量暴露环境有害因素对神经行为发育的损害效应。

Abstract

Fenvalerate, a synthetic pyrethroid insecticide, is an environmental endocrine disruptor and neurodevelopmental toxicant. An early report found that pubertal exposure to high-dose fenvalerate impaired cognitive and behavioral development. Here, we aimed to further investigate the effect of pubertal exposure to low-dose fenvalerate on cognitive and behavioral development. Mice were orally administered with fenvalerate (0.2, 1.0 and 5.0 mg/kg) daily from postnatal day (PND) 28 to PND56. Learning and memory were assessed by Morris water maze. Anxiety-related activities were detected by open-field and elevated plus-maze. Increased anxiety activities were observed only in females exposed to fenvalerate. Spatial learning and memory were damaged only in females exposed to fenvalerate. Histopathology observed numerous scattered shrinking neurons and nuclear pyknosis in hippocampal CA1 region. Neuronal density was reduced in hippocampal CA1 region of fenvalerate-exposed mice. Mechanistically, hippocampal thyroid hormone receptor (TR)β1 was down-regulated in a dose-dependent manner in females. In addition, TRα1 was declined only in females exposed to 5.0 mg/kg fenvalerate. Taken together, these suggests that pubertal exposure to low-dose fenvalerate impairs cognitive and behavioral development in a gender-dependent manner. Hippocampal TR signaling may be, at least partially, involved in fenvalerate-induced impairment of cognitive and behavioral development.

Yang Yang, Feng Zhan, Ye-Cheng Wang, Bo Wang, Meng-Xing Shi, Ce Guo, De-Xiang Xu, Xiu-Hong Meng.Pubertal fenvalerate exposure impairs cognitive and behavioral development partially through down-regulating hippocampal thyroid hormone receptor signaling. Toxicol Lett. 2020, 332: 192-201.