Cerebrovascular Pathology in Hypertriglyceridemic APOB-100 Transgenic Mice

Hypertriglyceridemia is not only a serious risk factor in the development of cardiovascular diseases, but it is linked to neurodegeneration, too. Previously, we generated transgenic mice overexpressing the human APOB-100 protein, a mouse model of human atherosclerosis. In this model we observed high...

Teljes leírás

Elmentve itt :
Bibliográfiai részletek
Szerzők: Hoyk Zsófia
Tóth Erzsébet Melinda
Lénárt Nikolett
Nagy Dóra
Dukay Brigitta
Zvara Ágnes
Seprényi György
Kincses András
Walter Fruzsina
Veszelka Szilvia
Barabási Beáta
Harazin András
Kittel Ágnes
Puskás László
Penke Botond
Vigh László
Deli Mária Anna
Sántha Miklós
Dokumentumtípus: Cikk
Megjelent: 2018
Sorozat:FRONTIERS IN CELLULAR NEUROSCIENCE 12
doi:10.3389/fncel.2018.00380

mtmt:30312141
Online Access:http://publicatio.bibl.u-szeged.hu/14906
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520 3 |a Hypertriglyceridemia is not only a serious risk factor in the development of cardiovascular diseases, but it is linked to neurodegeneration, too. Previously, we generated transgenic mice overexpressing the human APOB-100 protein, a mouse model of human atherosclerosis. In this model we observed high plasma levels of triglycerides, oxidative stress, tau hyperphosphorylation, synaptic dysfunction, cognitive impairment, increased neural apoptosis and neurodegeneration. Neurovascular dysfunction is recognized as a key factor in the development of neurodegenerative diseases, but the cellular and molecular events linking cerebrovascular pathology and neurodegeneration are not fully understood. Our aim was to study cerebrovascular changes in APOB-100 transgenic mice. We described the kinetics of the development of chronic hypertriglyceridemia in the transgenic animals. Increased blood-brain barrier permeability was found in the hippocampus of APOB-100 transgenic mice which was accompanied by structural changes. Using transmission electron microscopy, we detected changes in the brain capillary endothelial tight junction structure and edematous swelling of astrocyte endfeet. In brain microvessels isolated from APOB-100 transgenic animals increased Lox-1, Aqp4, and decreased Meox-2, Mfsd2a, Abcb1a, Lrp2, Glut-1, Nos2, Nos3, Vim, and in transgenic brains reduced Cdh2 and Gfap-σ gene expressions were measured using quantitative real-time PCR. We confirmed the decreased P-glycoprotein (ABCB1) and vimentin expression related to the neurovascular unit by immunostaining in transgenic brain sections using confocal microscopy. We conclude that in chronic hypertriglyceridemic APOB-100 transgenic mice both functional and morphological cerebrovascular pathology can be observed, and this animal model could be a useful tool to study the link between cerebrovascular pathology and neurodegeneration. 
700 0 1 |a Tóth Erzsébet Melinda  |e aut 
700 0 1 |a Lénárt Nikolett  |e aut 
700 0 1 |a Nagy Dóra  |e aut 
700 0 1 |a Dukay Brigitta  |e aut 
700 0 1 |a Zvara Ágnes  |e aut 
700 0 1 |a Seprényi György  |e aut 
700 0 1 |a Kincses András  |e aut 
700 0 1 |a Walter Fruzsina  |e aut 
700 0 1 |a Veszelka Szilvia  |e aut 
700 0 1 |a Barabási Beáta  |e aut 
700 0 1 |a Harazin András  |e aut 
700 0 1 |a Kittel Ágnes  |e aut 
700 0 1 |a Puskás László  |e aut 
700 0 1 |a Penke Botond  |e aut 
700 0 1 |a Vigh László  |e aut 
700 0 1 |a Deli Mária Anna  |e aut 
700 0 1 |a Sántha Miklós  |e aut 
856 4 0 |u http://publicatio.bibl.u-szeged.hu/14906/1/pdf  |z Dokumentum-elérés