Combined exposure of heat stress and ozone enhanced cognitive impairment via neuroinflammation and blood brain barrier disruption in male rats
Combined exposure of heat stress and ozone enhanced cognitive impairment via neuroinflammation and blood brain barrier disruption in male rats
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热应激和臭氧的联合暴露通过神经炎症和血脑屏障破坏增强了雄性大鼠的认知障碍
DOI：
10.1016/j.scitotenv.2022.159599
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发表时间：
2022
期刊：
影响因子：
--
通讯作者：
Lai-Bao Zhuo
中科院分区：
文献类型：
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作者：
Zhen Yan;Yu-Mei Liu;Wei-Dong Wu;Yuhan Jiang;Lai-Bao Zhuo
热应激（HS）暴露与认知功能障碍有关.在现实环境中，高温并不是单独发生的，臭氧（O3）和热浪通常共同存在于大气环境中。然而，O3暴露是否加重HS诱导的认知障碍及其可能的机制尚未得到实验研究。方法48只SD雄性道利大鼠随机分为对照组、HS组、O3组和HS + O3（HO 3）组。HS组和HO 3组大鼠每天早晨9：00 ~ 12：00暴露于40 °C，连续15 d。O_3组和HO_3组大鼠每天14：00 ~ 17：00暴露于0.7ppm的O_3中，连续15天。采用Morris水迷宫实验检测大鼠的认知能力。通过Western blot、ELISA、免疫组化和免疫荧光染色评价神经变性、胶质细胞活化、神经炎症、血脑屏障（BBB）破坏和细胞凋亡。进一步的研究表明，HS还可诱导大鼠海马神经胶质细胞活化、神经炎症和神经元凋亡，并降低ZO-1、claudin-5和occluding的表达，提示血脑屏障的破坏。令人印象深刻的是，如上所述，大鼠同时暴露于O3可能会加剧HS诱导的神经元效应。结论同时暴露于O3可能通过胶质细胞介导的神经炎症和BBB破坏促进大鼠HS诱导的认知障碍。
BackgroundHeat stress (HS) exposure has been linked to cognitive dysfunction. In reality, high temperature does not occur alone in environment, and ozone (O3) and heatwaves usually co-exist in atmospheric environment. However, whether O3exposure exacerbates HS-induced cognitive impairment and the potential underlying mechanisms have not been explored experimentally. The aim of this study was to determine the co-effects and mechanisms of HS and O3on the cognitive dysfunction.Methods48 Sprague Dawley male rats were randomly divided into 4 groups: control, HS, O3and HS plus O3(HO3) groups. Rats in HS and HO3group were exposed to 40 °C every morning from 9:00 to 12:00 for 15 consecutive days. While rats in O3and HO3groups were exposed to 0.7 ppm O3the same day from 14:00 to 17:00 for 15 days. Cognitive performance was examined with Morris water maze test. Neurodegeneration, glial activation, neuroinflammation, blood brain barrier (BBB) disruption and apoptosis were evaluated by Western blot, Elisa, immunohistochemistry and immunofluorescence staining.ResultsHS induced cognitive decline and neuronal damage in rats. Further studies showed that exposure of rats to HS could also induce glial activation, neuroinflammation and neuronal apoptosis in hippocampus, and decrease in the expressions of ZO-1, claudin-5 and occluding, indicative of BBB disruption. Impressively, the neuronal effects induced by HS, as depicted above, could be worsened by co-exposure to O3in rats.ConclusionsCo-exposure to O3promotes HS-induced cognitive impairment in rats possibly through glial-mediated neuroinflammation and BBB disruption.