Deltamethrin-Evoked ER Stress Promotes Neuroinflammation in the Adult Mouse Hippocampus.
Deltamethrin-Evoked ER Stress Promotes Neuroinflammation in the Adult Mouse Hippocampus.
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DOI：
10.3390/cells11121961
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发表时间：
2022-06-18
期刊：
影响因子：
6
通讯作者：
Molina, Maria A.
中科院分区：
文献类型：
--
作者：
Hossain, Muhammad M.;Toltin, Abigail C.;Gamba, Laura M.;Molina, Maria A.
内质网（ER）应激和神经炎症参与许多神经退行性疾病的发病机制。以前，我们报道了暴露于拟除虫菊酯类杀虫剂溴氰菊酯导致海马ER应激细胞凋亡，神经发生减少和学习缺陷的成年雄性小鼠。最近，我们发现溴氰菊酯暴露也增加了BV 2细胞中神经炎症的标志物。在这里，我们研究了暴露于溴氰菊酯后内质网应激和神经炎症之间的潜在机制联系。我们发现，重复经口暴露于溴氰菊酯（3 mg/kg）30天导致海马中小胶质细胞活化，并增加TNF-α、IL-1β、IL-6、gp 91 phox、4 HNE和iNOS的基因表达和蛋白水平。这些变化之前，诱导ER应激的CHOP，ATF-4，和GRP 78的蛋白水平在海马中显着增加。为了确定ER应激的诱导是否触发炎症反应，我们用小鼠小胶质细胞（MMC）系进行了另外的实验。在存在或不存在salubrinal（一种ER应激因子eIF 2 α的药理学抑制剂）的情况下，用0-5 µM溴氰菊酯处理MMC 24-48 h。我们发现salubrinal（50 µM）可防止溴氰菊酯诱导的ER应激，如CHOP和ATF-4水平降低所示，并减弱MMC中GSH、4-HNE、gp 91 phox、iNOS、ROS、TNF-α、IL-1β和IL-6的水平。总之，这些结果表明，溴氰菊酯暴露导致ER应激介导的神经炎症，随后可能导致小鼠神经变性和认知障碍。
Endoplasmic reticulum (ER) stress and neuroinflammation are involved in the pathogenesis of many neurodegenerative disorders. Previously, we reported that exposure to pyrethroid insecticide deltamethrin causes hippocampal ER stress apoptosis, a reduction in neurogenesis, and learning deficits in adult male mice. Recently, we found that deltamethrin exposure also increases the markers of neuroinflammation in BV2 cells. Here, we investigated the potential mechanistic link between ER stress and neuroinflammation following exposure to deltamethrin. We found that repeated oral exposure to deltamethrin (3 mg/kg) for 30 days caused microglial activation and increased gene expressions and protein levels of TNF-α, IL-1β, IL-6, gp91phox, 4HNE, and iNOS in the hippocampus. These changes were preceded by the induction of ER stress as the protein levels of CHOP, ATF-4, and GRP78 were significantly increased in the hippocampus. To determine whether induction of ER stress triggers the inflammatory response, we performed an additional experiment with mouse microglial cell (MMC) line. MMCs were treated with 0–5 µM deltamethrin for 24–48 h in the presence or absence of salubrinal, a pharmacological inhibitor of the ER stress factor eIF2α. We found that salubrinal (50 µM) prevented deltamethrin-induced ER stress, as indicated by decreased levels of CHOP and ATF-4, and attenuated the levels of GSH, 4-HNE, gp91phox, iNOS, ROS, TNF-α, IL-1β, and IL-6 in MMCs. Together, these results demonstrate that exposure to deltamethrin leads to ER stress-mediated neuroinflammation, which may subsequently contribute to neurodegeneration and cognitive impairment in mice.
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影响因子：
9.3
作者：
Dohi K;Ohtaki H;Nakamachi T;Yofu S;Satoh K;Miyamoto K;Song D;Tsunawaki S;Shioda S;Aruga T
通讯作者：
Aruga T
DOI：
10.1186/s13195-015-0126-1
发表时间：
2015
期刊：
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影响因子：
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作者：
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通讯作者：
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影响因子：
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作者：
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通讯作者：
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影响因子：
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作者：
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通讯作者：
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影响因子：
4.3
作者：
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通讯作者：
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