Alterations of Gut-Derived Melatonin in Neurobehavioral Impairments Caused by Zinc Oxide Nanoparticles

作者全名："Yang, Cantao; Lu, Zhaohong; Xia, Yinyin; Zhang, Jun; Zou, Zhen; Chen, Chengzhi; Wang, Xiaoliang; Tian, Xin; Cheng, Shuqun; Jiang, Xuejun"

作者地址："[Yang, Cantao; Lu, Zhaohong; Xia, Yinyin; Chen, Chengzhi; Cheng, Shuqun] Chongqing Med Univ, Sch Publ Hlth, Dept Occupat & Environm Hlth, Chongqing 400016, Peoples R China; [Zhang, Jun; Zou, Zhen] Chongqing Med Univ, Inst Life Sci, Mol Biol Lab Resp Dis, Chongqing 400016, Peoples R China; [Zhang, Jun; Zou, Zhen; Chen, Chengzhi; Cheng, Shuqun; Jiang, Xuejun] Chongqing Med Univ, Res Ctr Environm & Human Hlth, Sch Publ Hlth, Chongqing 400016, Peoples R China; [Wang, Xiaoliang] Chongqing Med Univ, Univ Town Hosp, Med Sci Res Ctr, Chongqing 401331, Peoples R China; [Tian, Xin] Chongqing Med Univ, Dept Neurol, Affiliated Hosp 1, Chongqing, Peoples R China; [Jiang, Xuejun] Chongqing Med Univ, Ctr Expt Teaching Publ Hlth, Expt Teaching & Management Ctr, Chongqing 400016, Peoples R China; [Cheng, Shuqun; Jiang, Xuejun] Chongqing Med Univ, Res Ctr Environm & Human Hlth, Sch Publ Hlth, 1 Yixueyuan Rd, Chongqing 400016, Peoples R China"

通信作者："Cheng, SQ; Jiang, XJ (通讯作者)，Chongqing Med Univ, Res Ctr Environm & Human Hlth, Sch Publ Hlth, 1 Yixueyuan Rd, Chongqing 400016, Peoples R China."

来源：INTERNATIONAL JOURNAL OF NANOMEDICINE

ESI学科分类：PHARMACOLOGY & TOXICOLOGY

WOS号：WOS:000967816800001

JCR分区：Q1

影响因子：6.6

年份：2023

卷号：18

期号：　

开始页：1899

结束页：1914

文献类型：Article

关键词：gut -derived melatonin; neurobehavioral impairment; transcriptome sequencing; zinc oxide nanoparticle exposure

摘要："Purpose: The widespread use of zinc oxide nanoparticles (ZnONPs) has raised concerns about its potential toxicity. Melatonin is a neurohormone with tremendous anti-toxic effects. The enterochromaffin cells are an essential source of melatonin in vivo. However, studies on the effects of ZnONPs on endogenous melatonin are minimal. In the present study, we aimed to investigate the effects of ZnONPs exposure on gut-derived melatonin.Methods: In the present study, 64 adult male mice were randomly and equally divided into four groups, and each group was exposed to ZnONPs (0, 6.5, 13, 26 mg/kg/day) for 30 days. Subsequently, the neurobehavioral changes were observed. The effects of ZnONPs on the expression of melatonin-related genes arylalkylamine N-acetyltransferase (Aanat), melatonin receptor1A (Mt1/Mtnr1a), melatonin receptor1B (Mt2/Mtnr1b), and neuropeptide Y (Npy) on melatonin synthesis and secretion in duodenum, jejunum, ileum and colon during day and night were also assessed.Results: The results revealed that oral exposure to ZnONPs induced impairments of locomotor activity and anxiety-like behavior in adult mice during the day. The transcriptional analysis of brain tissues revealed that exposure to ZnONPs caused profound effects on genes and transcriptional signaling pathways associated with melatonin synthesis and metabolic processes during the day and night. We also observed that, in the duodenum, jejunum, ileum and colon sites, ZnONPs resulted in a significant reduction in the expression of the gut-derived melatonin rate-limiting enzyme Aanat, the membrane receptors Mt1 and Mt2 and Npy during the day and night.Conclusion: Taken together, this is the first study shows that oral exposure to ZnONPs interferes with melatonin synthesis and secretion in different intestinal segments of adult mice. These findings will provide novelty insights into the neurotoxic mechanisms of ZnONPs and suggest an alternative strategy for the prevention of ZnONP neurotoxicity."

基金机构：NSFC [82001378]; Basic Research and Frontier Exploration Project of Yuzhong District [20180116]; Natural Science Foundation of Chongqing [No.cstc2019jcyj- msxmX0294]; Science and Technology Research Program of Chongqing Municipal Education Commission [KJQN202000444]

基金资助正文：Acknowledgments This study was supported by NSFC (Grant No. 82001378) ; the Basic Research and Frontier Exploration Project of Yuzhong District (Grant No. 20180116) ; Natural Science Foundation of Chongqing (Grant No.cstc2019jcyj- msxmX0294) ; Science and Technology Research Program of Chongqing Municipal Education Commission (Grant No. KJQN202000444) .