Polystyrene microplastics induce anxiety via HRAS derived PERK-NF-κB pathway

Li, Guanjun1; Liu, Xueyan1; Sun, Xin2; Huang, Ling1; Kuang, Wenhua1; Ou, Jinhuan1; Zhang, Junzhe3,4; Zhang, Ziyue1; Li, Huiying5; Tang, Huan3,4; Feng, Chenran3,4; Gu, Liwei3,4; Yang, Chuanbin1; Peili, Wang7; Wang, Jigang1,3,4,5,6

2024-03-01

10.1016/j.envint.2024.108543

ENVIRONMENT INTERNATIONAL   影响因子和分区

0160-4120

1873-6750

Exposure to environmentally hazardous substances is recognized as a significant risk factor for neurological associated disorders. Among these substances, polystyrene microplastics (PS -MPs), widely utilized in various consumer products, have been reported to exhibit neurotoxicity. However, the potential association of PS -MPs with abnormal anxiety behaviors, along with the underlying molecular mechanisms and key proteins involved, remains insufficiently explored. Here, we delineated the potential mechanisms of PS -MPs -induced anxiety through proteomics and molecular investigations. We characterized the PS -MPs, observed their accumulation in the brain, leading to anxiety -like behavior in mice, which is correlated with microglia activation and pro -inflammatory response. Consistent with these findings, our studies on BV2 microglia cells showed that PSMPs activated NF-kappa B-mediated inflammation resulting in the upregulation of pro -inflammatory cytokines such as TNF alpha and IL-1 beta. Of particular significance, HRAS was identified as a key factor in the PS -MPs induced proinflammatory response through whole proteomics analysis, and knockdown of H-ras effectively inhibited PSMPs induced PERK-NF-kappa B activation and associated pro -inflammatory response in microglia cells. Collectively, our findings highlight that PS -MPs induce anxiety of mice via the activation of the HRAS-derived PERK-NF-kappa B pathway in microlglia. Our results contribute valuable insights into the molecular mechanisms of PS -MPsinduced anxiety, and may offer implications for addressing neurotoxicity and prevention the adverse effects of environmentally hazardous substances, including microplastics.

Polystyrene microplastics Environmental toxicology Analytical chemistry

SCI ; EI

英语

第一 ; 通讯

Scientific and technological innovation project of China Academy of Chinese Medical Sciences["CI2023D003","CI2021B014"] ; Innovation Team and Talents Cultivation Program of National Administration of Traditional Chinese Medicine[ZYYCXTD-C-202002] ; CACMS Innovation Fund["CI2023E002","CI2021A05101","CI2021A05104"] ; Science and Technology Foundation of Shenzhen[JCYJ20210324115800001] ; Shenzhen Medical Research Fund[B2302051] ; Distinguished Expert Project of Sichuan Province Tianfu Scholar[CW202002] ; Shenzhen Key Laboratory of Prevention and Treatment of Severe Infections[ZDSYS20200811142804014] ; Shenzhen Science and Technology Innovation Committee (SZSTI)[RCYX20221008092950121] ; National Natural Science Foundation of China[82070517] ; Major scientific research project of Shenzhen People's Hospital[SYWGSJCYJ202202] ; Natural Science Foundation of Shenzhen["JCYJ20230807111911024","JCYJ20230807111959039"] ; China Postdoctoral Science Foundation[2023M741600]

Environmental Sciences & Ecology

Environmental Sciences

WOS:001208513700001

PERGAMON-ELSEVIER SCIENCE LTD

ENVIRONMENT/ECOLOGY

Web of Science

1.Southern Univ Sci & Technol, Affiliated Hosp 1, Shenzhen Peoples Hosp, Dept Critical Med,Shenzhen Clin Res Ctr Geriatr, Shenzhen 518020, Guangdong, Peoples R China
2.Southern Univ Sci & Technol, Affiliated Hosp 1, Shenzhen Peoples Hosp, Dept Cardiol,Shenzhen Cardiovasc Minimally Invas M, Shenzhen 518020, Guangdong, Peoples R China
3.China Acad Chinese Med Sci, State Key Lab Qual Ensurance & Sustainable Use Dao, Artemisinin Res Ctr, Beijing 100700, Peoples R China
4.China Acad Chinese Med Sci, Inst Chinese Mat Med, Beijing 100700, Peoples R China
5.Southern Med Univ, Dongguan Maternal & Child Hlth Care Hosp, Postdoctoral Innovat Practice Base, Dongguan 523125, Guangdong, Peoples R China
6.Henan Univ, Sch Pharm, State Key Lab Antiviral Drugs, Kaifeng 475004, Peoples R China
7.China Acad Chinese Med Sci, Xiyuan Hosp, Natl Clin Res Ctr Chinese Med Cardiol, Beijing, Peoples R China

Li, Guanjun,Liu, Xueyan,Sun, Xin,et al. Polystyrene microplastics induce anxiety via HRAS derived PERK-NF-κB pathway[J]. ENVIRONMENT INTERNATIONAL,2024,185.

Li, Guanjun.,Liu, Xueyan.,Sun, Xin.,Huang, Ling.,Kuang, Wenhua.,...&Wang, Jigang.(2024).Polystyrene microplastics induce anxiety via HRAS derived PERK-NF-κB pathway.ENVIRONMENT INTERNATIONAL,185.

Li, Guanjun,et al."Polystyrene microplastics induce anxiety via HRAS derived PERK-NF-κB pathway".ENVIRONMENT INTERNATIONAL 185(2024).