Mechanistic Link of ER Stress and Neuroinflammation Following Pyrethroid Exposure

拟除虫菊酯暴露后内质网应激与神经炎症的机制联系

• 批准号: 10772236
• 负责人: Muhammad M Hossain
• 金额: $ 1.81万
• 依托单位: FLORIDA INTERNATIONAL UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-04-25 至 2023-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10772236
• 关键词: Adult; Aging; Agriculture; Apoptotic; Attenuated; Cell Death; Cells; Chronic; Cognitive deficits; Doctor of Philosophy; Environmental Health; Exposure to; Future; Hippocampus; Impaired cognition; Impairment; Inflammation Mediators; Inflammatory; Insecticides; Knowledge; Learning; Link; Mediating; Microglia; Mus; Nerve Degeneration; Neurodegenerative Disorders; Occupational Exposure; Oxidative Stress; Pathogenesis; Pathway interactions; Pest Control; Pesticides; Production; Public Health; Reporting; Students; TNF gene; Toxic Environmental Substances; Weather; adult neurogenesis; college; decamethrin; endoplasmic reticulum stress; experience; health science research; nervous system disorder; neurogenesis; neuroinflammation; pyrethroid

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.

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病变和认知功能障碍的发病机制 疾病。当细胞感知到强健、持续的 ER 应激水平时，UPR 功能就会发挥作用。 受损并触发炎症和细胞凋亡途径的激活， 因此导致慢性和持续性神经退行性变和成人功能障碍 神经发生。暴露于包括杀虫剂在内的环境毒物已被证明 ER应激和与神经变性相关的神经炎症的致病因素 神经系统疾病。拟除虫菊酯是应用最广泛的一类杀虫剂来控制 公共卫生、农业和住宅环境中的害虫。重要的是，认知障碍 据报道，因职业原因接触拟除虫菊酯的成年人中存在这种情况。在之前的研究中，我们有 研究表明，重复接触拟除虫菊酯会诱发内质网应激、细胞凋亡、细胞分裂 成年小鼠的海马神经发生以及学习和认知缺陷。最近，我们 据报道，拟除虫菊酯杀虫剂可激活小胶质细胞并增加主要 小胶质细胞中的炎症介质 TNF-α 和 ROS 以及成人重复暴露 溴氰菊酯会导致成年小鼠海马体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主要机制 溴氰菊酯会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 ER 应激衰减的天气抑制 暴露于溴氰菊酯后小鼠海马体的神经炎症。

项目成果

Tributyltin-induced Ca(2+) mobilization via L-type voltage-dependent Ca(2+) channels in PC12 cells.

PC12 细胞中三丁基锡通过 L 型电压依赖性 Ca(2) 通道诱导 Ca(2) 动员。

• DOI: 10.1016/j.etap.2009.02.006
• 发表时间: 2009
• 期刊: Environmental toxicology and pharmacology
• 影响因子: 4.3
• 作者: Unno,Toshihiro;Iida,Ryoko;Okawa,Masashi;Matsuyama,Hayato;Hossain,MuhammadMubarak;Kobayashi,Haruo;Komori,Seiichi
• 通讯作者: Komori,Seiichi

The Preventive Effects of Salubrinal against Pyrethroid-Induced Disruption of Adult Hippocampal Neurogenesis in Mice.

• DOI: 10.3390/ijms242115614
• 发表时间: 2023-10-26
• 期刊: International journal of molecular sciences
• 影响因子: 5.6

Deltamethrin-Evoked ER Stress Promotes Neuroinflammation in the Adult Mouse Hippocampus.

• DOI: 10.3390/cells11121961
• 发表时间: 2022-06-18
• 期刊: CELLS
• 影响因子: 6
• 作者: Hossain, Muhammad M.;Toltin, Abigail C.;Gamba, Laura M.;Molina, Maria A.
• 通讯作者: Molina, Maria A.