{"title":"接触邻苯二甲酸二甲酯会通过 COX2 介导的神经炎症诱发认知障碍","authors":"","doi":"10.1016/j.ecoenv.2024.117039","DOIUrl":null,"url":null,"abstract":"<div><h3>Aim</h3><p>The present work explored the mechanism of dimethyl phthalate (DMP, the environmental contaminant) exposure in inducing cognitive impairment.</p></div><div><h3>Methods</h3><p>Targets and regulatory networks related to DMP-brain injury-cognitive impairment were analyzed through network pharmacology. DMP exposure was carried out to simulate DMP environmental uptake, whereas Morris water maze was performed for examining cognitive impairment. Additionally, inflammatory cytokine levels within tissues were measured. hematoxylin-eosin staining(H&E) and Nissl staining was conducted to examine brain tissue injury, while Western blot was carried out for identifying protein levels. After applying.Small interfering RNA(siRNA-COX2) and celecoxib-COX2 inhibitors separately, we analyzed impacts of DMP. Besides, in vitro experiments were performed to analyze impacts of DMP on microglial activation.</p></div><div><h3>Results</h3><p>As suggested by network pharmacology,Cyclooxygenase-2-PTGS2 (COX2) showed significant relation to DMP, and it exerted its effect via COX2. Following DMP exposure, mice experienced obvious cognitive impairment and brain damage, besides, microglial cells were activated, and inflammatory cytokines were up-regulated. Applying siRNA-COX2 and celecoxib-COX2 suppressed DMP’s impact and mitigated mouse cognitive impairment. Based on in vitro analysis, DMP led to microglial activation and neuroinflammation.</p></div><div><h3>Conclusion</h3><p>DMP exposure causes neuroinflammation via the COX2-regulated microglial activation, thus leading to cognitive impairment. COX2 may serve as the key action target of DMP.</p></div>","PeriodicalId":303,"journal":{"name":"Ecotoxicology and Environmental Safety","volume":null,"pages":null},"PeriodicalIF":6.2000,"publicationDate":"2024-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0147651324011151/pdfft?md5=72918b64de55c2af32baeca010290244&pid=1-s2.0-S0147651324011151-main.pdf","citationCount":"0","resultStr":"{\"title\":\"Dimethyl phthalate exposure induces cognitive impairment via COX2-mediated neuroinflammation\",\"authors\":\"\",\"doi\":\"10.1016/j.ecoenv.2024.117039\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div><h3>Aim</h3><p>The present work explored the mechanism of dimethyl phthalate (DMP, the environmental contaminant) exposure in inducing cognitive impairment.</p></div><div><h3>Methods</h3><p>Targets and regulatory networks related to DMP-brain injury-cognitive impairment were analyzed through network pharmacology. DMP exposure was carried out to simulate DMP environmental uptake, whereas Morris water maze was performed for examining cognitive impairment. Additionally, inflammatory cytokine levels within tissues were measured. hematoxylin-eosin staining(H&E) and Nissl staining was conducted to examine brain tissue injury, while Western blot was carried out for identifying protein levels. After applying.Small interfering RNA(siRNA-COX2) and celecoxib-COX2 inhibitors separately, we analyzed impacts of DMP. Besides, in vitro experiments were performed to analyze impacts of DMP on microglial activation.</p></div><div><h3>Results</h3><p>As suggested by network pharmacology,Cyclooxygenase-2-PTGS2 (COX2) showed significant relation to DMP, and it exerted its effect via COX2. Following DMP exposure, mice experienced obvious cognitive impairment and brain damage, besides, microglial cells were activated, and inflammatory cytokines were up-regulated. Applying siRNA-COX2 and celecoxib-COX2 suppressed DMP’s impact and mitigated mouse cognitive impairment. Based on in vitro analysis, DMP led to microglial activation and neuroinflammation.</p></div><div><h3>Conclusion</h3><p>DMP exposure causes neuroinflammation via the COX2-regulated microglial activation, thus leading to cognitive impairment. COX2 may serve as the key action target of DMP.</p></div>\",\"PeriodicalId\":303,\"journal\":{\"name\":\"Ecotoxicology and Environmental Safety\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":6.2000,\"publicationDate\":\"2024-09-12\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.sciencedirect.com/science/article/pii/S0147651324011151/pdfft?md5=72918b64de55c2af32baeca010290244&pid=1-s2.0-S0147651324011151-main.pdf\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Ecotoxicology and Environmental Safety\",\"FirstCategoryId\":\"93\",\"ListUrlMain\":\"https://www.sciencedirect.com/science/article/pii/S0147651324011151\",\"RegionNum\":2,\"RegionCategory\":\"环境科学与生态学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"ENVIRONMENTAL SCIENCES\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Ecotoxicology and Environmental Safety","FirstCategoryId":"93","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S0147651324011151","RegionNum":2,"RegionCategory":"环境科学与生态学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"ENVIRONMENTAL SCIENCES","Score":null,"Total":0}
Dimethyl phthalate exposure induces cognitive impairment via COX2-mediated neuroinflammation
Aim
The present work explored the mechanism of dimethyl phthalate (DMP, the environmental contaminant) exposure in inducing cognitive impairment.
Methods
Targets and regulatory networks related to DMP-brain injury-cognitive impairment were analyzed through network pharmacology. DMP exposure was carried out to simulate DMP environmental uptake, whereas Morris water maze was performed for examining cognitive impairment. Additionally, inflammatory cytokine levels within tissues were measured. hematoxylin-eosin staining(H&E) and Nissl staining was conducted to examine brain tissue injury, while Western blot was carried out for identifying protein levels. After applying.Small interfering RNA(siRNA-COX2) and celecoxib-COX2 inhibitors separately, we analyzed impacts of DMP. Besides, in vitro experiments were performed to analyze impacts of DMP on microglial activation.
Results
As suggested by network pharmacology,Cyclooxygenase-2-PTGS2 (COX2) showed significant relation to DMP, and it exerted its effect via COX2. Following DMP exposure, mice experienced obvious cognitive impairment and brain damage, besides, microglial cells were activated, and inflammatory cytokines were up-regulated. Applying siRNA-COX2 and celecoxib-COX2 suppressed DMP’s impact and mitigated mouse cognitive impairment. Based on in vitro analysis, DMP led to microglial activation and neuroinflammation.
Conclusion
DMP exposure causes neuroinflammation via the COX2-regulated microglial activation, thus leading to cognitive impairment. COX2 may serve as the key action target of DMP.
期刊介绍:
Ecotoxicology and Environmental Safety is a multi-disciplinary journal that focuses on understanding the exposure and effects of environmental contamination on organisms including human health. The scope of the journal covers three main themes. The topics within these themes, indicated below, include (but are not limited to) the following: Ecotoxicology、Environmental Chemistry、Environmental Safety etc.