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变和认知功能障碍的发病机制 疾病。当细胞感受到强健、持续的内质网应激水平时，UPR功能是 炎症和凋亡通路的受损和激活被触发，这 从而导致成人慢性和持续性的神经变性和损害 神经发生。暴露于环境毒物，包括杀虫剂，已显示为 内质网应激的致病因素，以及与神经变性和 神经系统疾病。拟除虫菊酯是使用最广泛的杀虫剂 公共卫生、农业和住宅环境中的害虫。重要的是，认知障碍有 据报道，在职业接触拟除虫菊酯的成年人中。在之前的研究中，我们有 结果表明，拟除虫菊酯反复暴露可诱导内质网应激、细胞凋亡、细胞周期紊乱 成年小鼠的海马神经发生与学习和认知缺陷。最近，我们 报道称，拟除虫菊酯杀虫剂激活小胶质细胞，增加主要 炎性介质肿瘤坏死因子-α和ROS在小胶质细胞中的表达及成人反复接触 溴氰菊酯在成年小鼠的海马区引起氧化应激和神经炎症。 这些结果提示内质网应激介导的神经炎症可能是其主要机制之一。 溴氰菊酯对大鼠海马神经发生和认知功能障碍的影响 接触溴氰菊酯。在这里，我们将确定天气对内质网应激衰减的抑制 溴氰菊酯暴露后小鼠海马区的神经炎症。

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.