Publications

BibTex format

@misc{McArthur:2018,
author = {McArthur, S and Carvalho, A and Fonseca, S and Snelling, T and Nicholson, J and Glen, R and Carding, S and Hoyles, L},
title = {Effects of gut-derived trimethylamines on the blood–brain barrier},
type = {Poster},
url = {http://hdl.handle.net/10044/1/62968},
year = {2018}
}

Download

RIS format (EndNote, RefMan)

TY  - GEN
AB  - Introduction: The gut microbiota and its metabolites exert significant effects on host health, with disturbances to composition and function associated with conditions including obesity, type II diabetes and, more recently, Alzheimer’s disease (AD). Communication between microbes and the host can take a number of forms, but central to all of them is a role for gut-derived microbial metabolites, with trimethylamine N-oxide (TMAO) and its precursor trimethylamine (TMA) being important examples. TMA produced by gut bacteria is converted to TMAO in the liver by flavin monooxygenases whereupon it enters the circulation. TMAO was recently identified as potentially important in genetic pathways associated with AD, and has been shown to influence peripheral vascular function. Given these links, the key position of the cerebral vasculature as the major interface between circulating molecules and the brain, and evidence that deficits in blood–brain barrier (BBB) function occur early in AD, we investigated the effects of TMAO and TMA on key BBB properties in vitro and in vivo.Materials and Methods: Male C57Bl/6 mice (n=4-5) were used to examine the effect of TMAO treatment (1.8 mg/kg, 2 h, dose equivalent to circulating human concentrations) upon BBB permeability in vivo, assessed by Evans’ blue dye extravasation. TMA was not investigated as the average mouse plasma concentration of this methylamine is substantially greater than that seen in humans (TMAO-to-TMA ratio 1:10 in mice, 10:1 in humans).Human hCMEC/D3 cerebromicrovascular cells were used as an in vitro model of the BBB to investigate the effects of 24 h treatment with human physiologically relevant doses of TMAO (40 μM) and TMA (0.4 μM), studying (i) functional barrier properties of cell monolayers and (ii) gene expression. Results: Administration of TMAO to mice enhanced BBB integrity above baseline after 2 h treatment (p<0.05). Similarly, in vitro exposure of hCMEC/D3 cells to TMAO enhanc
AU  - McArthur,S
AU  - Carvalho,A
AU  - Fonseca,S
AU  - Snelling,T
AU  - Nicholson,J
AU  - Glen,R
AU  - Carding,S
AU  - Hoyles,L
PY  - 2018///
TI  - Effects of gut-derived trimethylamines on the blood–brain barrier
UR  - http://hdl.handle.net/10044/1/62968
ER  -

Download

ProfessorRobertGlen

Contact

Location

Summary

Citation

BibTex format

RIS format (EndNote, RefMan)