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2017 ; 16
(2
): 414-421
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Melatonin alleviates lipopolysaccharide-compromised integrity of blood-brain
barrier through activating AMP-activated protein kinase in old mice
#MMPMID28156052
Wang X
; Xue GX
; Liu WC
; Shu H
; Wang M
; Sun Y
; Liu X
; Sun YE
; Liu CF
; Liu J
; Liu W
; Jin X
Aging Cell
2017[Apr]; 16
(2
): 414-421
PMID28156052
show ga
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.