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Pericyte degeneration causes white matter dysfunction in the mouse central nervous system.
dc.creator | Montagne, Axel | |
dc.creator | Nikolakopoulou, Angeliki M | |
dc.creator | Zhao, Zhen | |
dc.creator | Sagare, Abhay P | |
dc.creator | Si, Gabriel | |
dc.creator | Lazic, Divna | |
dc.creator | Barnes, Samuel R | |
dc.creator | Daianu, Madelaine | |
dc.creator | Ramanathan, Anita | |
dc.creator | Go, Ariel | |
dc.creator | Lawson, Erica J | |
dc.creator | Wang, Yaoming | |
dc.creator | Mack, William J | |
dc.creator | Thompson, Paul M | |
dc.creator | Schneider, Julie A | |
dc.creator | Varkey, Jobin | |
dc.creator | Langen, Ralf | |
dc.creator | Mullins, Eric | |
dc.creator | Jacobs, Russell E | |
dc.creator | Zlokovic, Berislav V | |
dc.date.accessioned | 2018-03-16T10:22:40Z | |
dc.date.available | 2018-03-16T10:22:40Z | |
dc.date.issued | 2018 | |
dc.identifier.issn | 1078-8956 | |
dc.identifier.uri | http://www.nature.com/doifinder/10.1038/nm.4482 | |
dc.identifier.uri | http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=PMC5840035 | |
dc.identifier.uri | https://radar.ibiss.bg.ac.rs/handle/123456789/3012 | |
dc.description.abstract | Diffuse white-matter disease associated with small-vessel disease and dementia is prevalent in the elderly. The biological mechanisms, however, remain elusive. Using pericyte-deficient mice, magnetic resonance imaging, viral-based tract-tracing, and behavior and tissue analysis, we found that pericyte degeneration disrupted white-matter microcirculation, resulting in an accumulation of toxic blood-derived fibrin(ogen) deposits and blood-flow reductions, which triggered a loss of myelin, axons and oligodendrocytes. This disrupted brain circuits, leading to white-matter functional deficits before neuronal loss occurs. Fibrinogen and fibrin fibrils initiated autophagy-dependent cell death in oligodendrocyte and pericyte cultures, whereas pharmacological and genetic manipulations of systemic fibrinogen levels in pericyte-deficient, but not control mice, influenced the degree of white-matter fibrin(ogen) deposition, pericyte degeneration, vascular pathology and white-matter changes. Thus, our data indicate that pericytes control white-matter structure and function, which has implications for the pathogenesis and treatment of human white-matter disease associated with small-vessel disease. | en |
dc.relation | US National Institute of Health grants NS100459, AG039452, NS034467 and AG023084 | |
dc.relation | Foundation Leducq Transatlantic Network of Excellence for the Study of Perivascular Spaces in Small Vessel Disease reference no. 16 CVD 05, and ES024936 | |
dc.rights | restrictedAccess | |
dc.source | Nature Medicine | |
dc.source | Nature Medicine | |
dc.title | Pericyte degeneration causes white matter dysfunction in the mouse central nervous system. | en |
dc.type | article | en |
dc.rights.license | ARR | |
dcterms.abstract | Злоковиц, Берислав В; Лазиц, Дивна; Монтагне, Axел; Николакопоулоу, Aнгелики М; Зхао, Зхен; Сагаре, Aбхаy П; Си, Габриел; Барнес, Самуел Р; Даиану, Маделаине; Раманатхан, Aнита; Го, Aриел; Лаwсон, Ерица Ј; Wанг, Yаоминг; Мацк, Wиллиам Ј; Тхомпсон, Паул М; Сцхнеидер, Јулие A; Варкеy, Јобин; Ланген, Ралф; Муллинс, Ериц; Јацобс, Русселл Е; | |
dc.rights.holder | © 2018 Nature America, Inc., part of Springer Nature | |
dc.citation.issue | 3 | |
dc.citation.volume | 24 | |
dc.identifier.doi | 10.1038/nm.4482 | |
dc.identifier.pmid | 29400711 | |
dc.identifier.scopus | 2-s2.0-85042940111 | |
dc.identifier.wos | 000426700900015 | |
dc.citation.apa | Montagne, A., Nikolakopoulou, A. M., Zhao, Z., Sagare, A. P., Si, G., Lazic, D., Barnes, S. R., et al. (2018). Pericyte degeneration causes white matter dysfunction in the mouse central nervous system. Nature Medicine, 24(3), 326–337. | |
dc.citation.vancouver | Montagne A, Nikolakopoulou AM, Zhao Z, Sagare AP, Si G, Lazic D, Barnes SR, Daianu M, Ramanathan A, Go A, Lawson EJ, Wang Y, Mack WJ, Thompson PM, Schneider JA, Varkey J, Langen R, Mullins E, Jacobs RE, Zlokovic B V. Pericyte degeneration causes white matter dysfunction in the mouse central nervous system. Nat Med. 2018;24(3):326–37. | |
dc.citation.spage | 326 | |
dc.citation.epage | 337 | |
dc.type.version | publishedVersion | en |
dc.citation.rank | aM21 |
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