Open AccessMelatonin alleviates lipopolysaccharide‐compromised integrity of blood–brain barrier through activating AMP ‐activated protein kinase in old mice
Author(s) -
Wang Xiaona,
Xue GaiXiu,
Liu WenCao,
Shu Hui,
Wang Mengwei,
Sun Yanyun,
Liu Xiaojing,
Sun Yi Eve,
Liu ChunFeng,
Liu Jie,
Liu Wenlan,
Jin Xinchun
Publication year - 2017
Publication title -
aging cell
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.103
H-Index - 140
eISSN - 1474-9726
pISSN - 1474-9718
DOI - 10.1111/acel.12572
Subject(s) - occludin , lipopolysaccharide , ampk , melatonin , tight junction , protein kinase a , endocrinology , medicine , amp activated protein kinase , biology , western blot , blood–brain barrier , kinase , microbiology and biotechnology , biochemistry , central nervous system , gene
Summary 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 (24–28 months of age) received melatonin (10 mg kg −1 day −1 , intraperitoneally, i.p.) or saline for one week before exposing to LPS (1 mg kg −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.