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热应激和臭氧联合暴露通过神经炎症和血脑屏障破坏导致雄性大鼠认知功能障碍。

Combined exposure of heat stress and ozone enhanced cognitive impairment via neuroinflammation and blood brain barrier disruption in male rats.

机构信息

International School of Public Health and One Health, Hainan Medical University, Haikou, China.

School of Public Health, Xinxiang Medical University, Xinxiang, China.

出版信息

Sci Total Environ. 2023 Jan 20;857(Pt 3):159599. doi: 10.1016/j.scitotenv.2022.159599. Epub 2022 Oct 21.

DOI:10.1016/j.scitotenv.2022.159599
PMID:36280063
Abstract

BACKGROUND

Heat stress (HS) exposure has been linked to cognitive dysfunction. In reality, high temperature does not occur alone in environment, and ozone (O) and heatwaves usually co-exist in atmospheric environment. However, whether O exposure 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 O on the cognitive dysfunction.

METHODS

48 Sprague Dawley male rats were randomly divided into 4 groups: control, HS, O and HS plus O (HO) groups. Rats in HS and HO group were exposed to 40 °C every morning from 9:00 to 12:00 for 15 consecutive days. While rats in O and HO groups were exposed to 0.7 ppm O the 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.

RESULTS

HS 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 O in rats.

CONCLUSIONS

Co-exposure to O promotes HS-induced cognitive impairment in rats possibly through glial-mediated neuroinflammation and BBB disruption.

摘要

背景

热应激(HS)暴露与认知功能障碍有关。实际上,高温在环境中不会单独存在,臭氧(O)和热浪通常在大气环境中共存。然而,O 暴露是否会加剧 HS 引起的认知障碍以及潜在的机制尚未通过实验探索。本研究旨在确定 HS 和 O 对认知功能障碍的共同作用和机制。

方法

48 只雄性 Sprague Dawley 大鼠随机分为 4 组:对照组、HS 组、O 组和 HS+O(HO)组。HS 和 HO 组大鼠每天上午 9:00 至 12:00 暴露于 40°C 下,连续 15 天。而 O 和 HO 组大鼠在同一天下午 14:00 至 17:00 暴露于 0.7 ppm O 下,连续 15 天。使用 Morris 水迷宫测试评估认知表现。通过 Western blot、Elisa、免疫组织化学和免疫荧光染色评估神经退行性变、神经胶质激活、神经炎症、血脑屏障(BBB)破坏和细胞凋亡。

结果

HS 导致大鼠认知能力下降和神经元损伤。进一步的研究表明,大鼠暴露于 HS 还可诱导海马中的神经胶质激活、神经炎症和神经元凋亡,并降低 ZO-1、claudin-5 和 occluding 的表达,表明 BBB 破坏。令人印象深刻的是,HS 引起的上述神经元效应可因大鼠的 O 共暴露而恶化。

结论

O 共暴露可促进 HS 引起的大鼠认知障碍,可能通过神经胶质介导的神经炎症和 BBB 破坏。

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