Mechanistic Link of ER Stress and Neuroinflammation Following Pyrethroid Exposure

内质网（ER）应激和神经炎症参与了 衰老和神经退行性疾病中神经退行性疾病和认知功能障碍的发病机制 疾病当细胞感受到强大的、持续水平的内质网应激时，UPR功能被激活。 炎症和凋亡途径的受损和激活被触发， 从而导致慢性和持续的神经变性和成年人的损伤。 神经发生暴露于环境毒物，包括农药，已被证明是 ER应激的病原体，以及与神经变性相关的神经炎症， 神经系统疾病。拟除虫菊酯是最广泛使用的一类杀虫剂， 公共卫生、农业和住宅环境中的害虫。重要的是，认知障碍 在职业接触拟除虫菊酯的成人中报告。在以前的研究中，我们 显示重复的拟除虫菊酯暴露诱导ER应激、凋亡性细胞死亡、 海马神经发生以及成年小鼠的学习和认知缺陷。最近我们 报告说，拟除虫菊酯杀虫剂激活小胶质细胞， 小胶质细胞中炎症介质TNF-α和ROS与成人反复暴露于 溴氰菊酯在成年小鼠海马体中引起氧化应激和神经炎症。 这些结果表明，内质网应激介导的神经炎症可能是一个主要机制 溴氰菊酯损害海马神经发生和认知功能障碍 溴氰菊酯暴露。在这里，我们将确定天气抑制ER应力衰减 溴氰菊酯暴露后小鼠海马神经炎症。

Endoplasmic reticulum (ER) stress and neuroinflammation have been involved in the pathogenesis of neurodegeneration and cognitive dysfunctions in aging and neurodegenerative diseases. When robust, sustained levels of ER stress are sensed by cells, UPR function is impaired and activation of inflammatory and apoptotic pathways are triggered, which consequently leads to chronic and persistent neurodegeneration and impairment of adult neurogenesis. Exposure to environmental toxicants, including pesticides have been shown as causative agents of ER stress, and neuroinflammation associated with neurodegeneration and neurological diseases. Pyrethroids are the most widely employed group of insecticides to control pests in public health, agriculture, and residential settings. Importantly, cognitive impairment has been reported in adults occupationally exposed to pyrethroids. In previous studies, we have shown that repeated pyrethroid exposure induced ER stress, apoptotic cell death, disruption of hippocampal neurogenesis, and learning and cognitive deficits in adult mice. Recently, we reported that pyrethroid insecticides activate microglia and increase production of major inflammatory mediators TNF-α and ROS in microglial cells and that repeated adult exposure to deltamethrin causes oxidative stress and neuroinflammation in the hippocampus of adult mice. These results suggest that ER stress-mediated neuroinflammation may be a primary mechanism by which deltamethrin impaired hippocampal neurogenesis and cognitive dysfunction following deltamethrin exposure. Here, we will determine the weather inhibition of ER stress attenuates neuroinflammation in the hippocampus in mice following deltamethrin exposure.