Xue Fan Wang, Robin Vigouroux, Michal Syonov, Yuriy Baglaenko, Angeliki M Nikolakopoulou, Dene Ringuette, Horea Rus, Peter V DiStefano, Suzie Dufour, Alireza P Shabanzadeh, Seunggi Lee, Bernhard K Mueller, Jason Charish, Hidekiyo Harada, Jason E Fish, Joan Wither, Thomas Wälchli, Jean-François Cloutier, Berislav V Zlokovic, Peter L Carlen, Philippe P Monnier
Liver failure causes breakdown of the Blood CNS Barrier (BCB) leading to damages of the Central-Nervous-System (CNS), however the mechanisms whereby the liver influences BCB-integrity remain elusive. One possibility is that the liver secretes an as-yet to be identified molecule(s) that circulate in the serum to directly promote BCB-integrity. To study BCB-integrity, we developed light-sheet imaging for three-dimensional analysis. We show that liver- or muscle-specific knockout of Hfe2/Rgmc induces BCB-breakdown, leading to accumulation of toxic-blood-derived fibrinogen in the brain, lower cortical neuron numbers, and behavioral deficits in mice...
February 3, 2024: Nature Communications