Matches in SemOpenAlex for { <https://semopenalex.org/work/W4360948476> ?p ?o ?g. }
- W4360948476 abstract "Abstract Background Impairment of the blood-brain barrier (BBB) is considered to be a common feature among neurodegenerative diseases, including Alzheimer’s, Parkinson’s and prion diseases. In prion disease, increased BBB permeability was reported 40 years ago, yet the mechanisms behind the loss of BBB integrity have never been explored. Recently, we showed that reactive astrocytes associated with prion diseases are neurotoxic. The current work examines the potential link between astrocyte reactivity and BBB breakdown. Results In prion-infected mice, the loss of BBB integrity and aberrant localization of aquaporin 4 (AQP4), a sign of retraction of astrocytic endfeet from blood vessels, were noticeable prior to disease onset. Gaps in cell-to-cell junctions along blood vessels, together with downregulation of Occludin, Claudin-5 and VE-cadherin, which constitute tight and adherens junctions, suggested that loss of BBB integrity is linked with degeneration of vascular endothelial cells. In contrast to cells isolated from non-infected adult mice, endothelial cells originating from prion-infected mice displayed disease-associated changes, including lower levels of Occludin, Claudin-5 and VE-cadherin expression, impaired tight and adherens junctions, and reduced trans-endothelial electrical resistance (TEER). Endothelial cells isolated from non-infected mice, when co-cultured with reactive astrocytes isolated from prion-infected animals or treated with media conditioned by the reactive astrocytes, developed the disease-associated phenotype observed in the endothelial cells from prion-infected mice. Reactive astrocytes were found to produce high levels of secreted IL-6, and treatment of endothelial monolayers originating from non-infected animals with recombinant IL-6 alone reduced their TEER. Remarkably, treatment with extracellular vesicles produced by normal astrocytes partially reversed the disease phenotype of endothelial cells isolated from prion-infected animals. Conclusions To our knowledge, the current work is the first to illustrate early BBB breakdown in prion disease and to document that reactive astrocytes associated with prion disease are detrimental to BBB integrity. Moreover, our findings suggest that the harmful effects are linked to proinflammatory factors secreted by reactive astrocytes." @default.
- W4360948476 created "2023-03-26" @default.
- W4360948476 creator A5024371705 @default.
- W4360948476 creator A5032924150 @default.
- W4360948476 creator A5042499250 @default.
- W4360948476 creator A5044367029 @default.
- W4360948476 creator A5046805885 @default.
- W4360948476 creator A5046940174 @default.
- W4360948476 creator A5066707030 @default.
- W4360948476 date "2023-03-25" @default.
- W4360948476 modified "2023-10-18" @default.
- W4360948476 title "Reactive astrocytes associated with prion disease impair the blood brain barrier" @default.
- W4360948476 cites W1559478955 @default.
- W4360948476 cites W1570470449 @default.
- W4360948476 cites W1837885345 @default.
- W4360948476 cites W1957113176 @default.
- W4360948476 cites W1963703759 @default.
- W4360948476 cites W1976914164 @default.
- W4360948476 cites W1978208782 @default.
- W4360948476 cites W1989150559 @default.
- W4360948476 cites W1993979927 @default.
- W4360948476 cites W2015541518 @default.
- W4360948476 cites W2018004489 @default.
- W4360948476 cites W2020243880 @default.
- W4360948476 cites W2022051519 @default.
- W4360948476 cites W2026523213 @default.
- W4360948476 cites W2043803772 @default.
- W4360948476 cites W2050589760 @default.
- W4360948476 cites W2053636966 @default.
- W4360948476 cites W2057293794 @default.
- W4360948476 cites W2059149362 @default.
- W4360948476 cites W2064169330 @default.
- W4360948476 cites W2065698593 @default.
- W4360948476 cites W2067975188 @default.
- W4360948476 cites W2095249301 @default.
- W4360948476 cites W2097573610 @default.
- W4360948476 cites W2099448948 @default.
- W4360948476 cites W2103037576 @default.
- W4360948476 cites W2118122091 @default.
- W4360948476 cites W2125236750 @default.
- W4360948476 cites W2131902093 @default.
- W4360948476 cites W2143452090 @default.
- W4360948476 cites W2144065167 @default.
- W4360948476 cites W2148130200 @default.
- W4360948476 cites W2150824641 @default.
- W4360948476 cites W2167183660 @default.
- W4360948476 cites W2167564565 @default.
- W4360948476 cites W2169849112 @default.
- W4360948476 cites W2170724437 @default.
- W4360948476 cites W2176259330 @default.
- W4360948476 cites W2202769705 @default.
- W4360948476 cites W2227183631 @default.
- W4360948476 cites W2314634699 @default.
- W4360948476 cites W2337252009 @default.
- W4360948476 cites W2406691442 @default.
- W4360948476 cites W2413269728 @default.
- W4360948476 cites W2425692864 @default.
- W4360948476 cites W2463544644 @default.
- W4360948476 cites W2518260520 @default.
- W4360948476 cites W2518673348 @default.
- W4360948476 cites W2548267094 @default.
- W4360948476 cites W2564793794 @default.
- W4360948476 cites W2572710398 @default.
- W4360948476 cites W2616216465 @default.
- W4360948476 cites W2790346667 @default.
- W4360948476 cites W2792813804 @default.
- W4360948476 cites W2807256450 @default.
- W4360948476 cites W2890224686 @default.
- W4360948476 cites W2893668476 @default.
- W4360948476 cites W2903369523 @default.
- W4360948476 cites W2904646996 @default.
- W4360948476 cites W2910182944 @default.
- W4360948476 cites W2912925231 @default.
- W4360948476 cites W2950636079 @default.
- W4360948476 cites W2964295256 @default.
- W4360948476 cites W2980106772 @default.
- W4360948476 cites W2984701628 @default.
- W4360948476 cites W2998040352 @default.
- W4360948476 cites W3003228785 @default.
- W4360948476 cites W3012468343 @default.
- W4360948476 cites W3026306241 @default.
- W4360948476 cites W3032338792 @default.
- W4360948476 cites W3087458297 @default.
- W4360948476 cites W3119531196 @default.
- W4360948476 cites W3126943997 @default.
- W4360948476 cites W3134296362 @default.
- W4360948476 cites W3161937579 @default.
- W4360948476 cites W3164457652 @default.
- W4360948476 cites W3179750557 @default.
- W4360948476 cites W3200709465 @default.
- W4360948476 cites W3210054668 @default.
- W4360948476 cites W3215471537 @default.
- W4360948476 cites W4283731455 @default.
- W4360948476 cites W4290851113 @default.
- W4360948476 cites W4308147217 @default.
- W4360948476 doi "https://doi.org/10.1101/2023.03.21.533684" @default.
- W4360948476 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/36993690" @default.
- W4360948476 hasPublicationYear "2023" @default.
- W4360948476 type Work @default.
- W4360948476 citedByCount "0" @default.