机构：[1]Jiangsu Key Laboratory of Translational Research and Therapy for Neuro- Psycho-Diseases and Institute of Neuroscience, The Second Affiliated Hospital of Soochow University, Suzhou 215004, China[2]Suzhou Municipal Hospital, Suzhou 215002, China[3]Department of Emergency, Shanxi Provincial People’s Hospital, Taiyuan 030001, China[4]Translational Center for Stem Cell Research, Tongji Hospital, Stem Cell Research Center, Tongji University School of Medicine, Shanghai 200065, China[5]Department of Psychiatry and Biobehavioral Sciences, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA 90095, USA[6]Department of Neurology, Jiangsu Key Laboratory of Translational Research and Therapy for Neuro-Psycho-Diseases, The Second Affiliated Hospital of Soochow University, Soochow University, Suzhou 215004, China[7]The Central Laboratory, Shenzhen Second People’s Hospital, the First Affiliated Hospital of Shenzhen University, Shenzhen 518035, China
Blood-brain barrier (BBB) dysfunction is considered to be an early event in the pathogenesis of a variety of neurological diseases in old patients, and this could occur in old people even when facing common stress. However, the mechanism remains to be defined. In this study, we tested the hypothesis that decreased melatonin levels may account for the BBB disruption in old mice challenged with lipopolysaccharide (LPS), which mimicked the common stress of sepsis. Mice (24-28months of age) received melatonin (10mgkg(-1)day(-1), intraperitoneally, i.p.) or saline for one week before exposing to LPS (1mgkg(-1), i.p.). Evan's blue dye (EB) and immunoglobulin G (IgG) leakage were used to assess BBB permeability. Immunostaining and Western blot were used to detect protein expression and distribution. Our results showed that LPS significantly increased BBB permeability in old mice accompanied by the degradation of tight junction proteins occludin and claudin-5, suppressed AMP-activated protein kinase (AMPK) activation, and elevated gp91(phox) protein expression. Interestingly, administration of melatonin for one week significantly decreased LPS-induced BBB disruption, AMPK suppression, and gp91(phox) upregualtion. Moreover, activation of AMPK with metformin significantly inhibited LPS-induced gp91(phox) upregualtion in endothelial cells. Taken together, our findings demonstrate that melatonin alleviates LPS-induced BBB disruption through activating AMPK and inhibiting gp91(phox) upregulation in old mice.
基金：
This work was supported by Soochow University Research startup fund
(Q421500113), by National Natural Science Foundation of China
(31271371, 81371328, 81571149, 81671145), by Natural Science
Foundation of Jiangsu Province of China (L221506415), and by a grant
from Shenzhen Science and Technology Innovation Commission
(KQCX20140521101427034). This work was also partly supported by
Priority Academic Program Development of Jiangsu Higher Education
Institutions of China.
第一作者机构：[1]Jiangsu Key Laboratory of Translational Research and Therapy for Neuro- Psycho-Diseases and Institute of Neuroscience, The Second Affiliated Hospital of Soochow University, Suzhou 215004, China
共同第一作者：
通讯作者：
通讯机构：[4]Translational Center for Stem Cell Research, Tongji Hospital, Stem Cell Research Center, Tongji University School of Medicine, Shanghai 200065, China[*1]Institute of Neuroscience, The Second Affiliated Hospital of Soochow University, Soochow University, Suzhou, 215004 China.[*2]the Central Laboratory, Shenzhen Second People’s Hospital, the First Affiliated Hospital of Shenzhen University, Shenzhen, China 518035.
推荐引用方式(GB/T 7714)：
Xiaona Wang ,Gai-Xiu Xue ,Wen-Cao Liu ,et al.Melatonin alleviates lipopolysaccharide-compromised integrity of blood-brain barrier through activating AMP-activated protein kinase in old mice[J].AGING CELL.2017,16(2):414-421.doi:10.1111/acel.12572.
APA：
Xiaona Wang,,Gai-Xiu Xue,,Wen-Cao Liu,,Hui Shu,,Mengwei Wang,...&Xinchun Jin.(2017).Melatonin alleviates lipopolysaccharide-compromised integrity of blood-brain barrier through activating AMP-activated protein kinase in old mice.AGING CELL,16,(2)
MLA：
Xiaona Wang,,et al."Melatonin alleviates lipopolysaccharide-compromised integrity of blood-brain barrier through activating AMP-activated protein kinase in old mice".AGING CELL 16..2(2017):414-421
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