Pericyte degeneration causes white matter dysfunction in the mouse central nervous system.
2018
Аутори:
Montagne, AxelNikolakopoulou, Angeliki M
Zhao, Zhen
Sagare, Abhay P
Si, Gabriel
Lazic, Divna
Barnes, Samuel R
Daianu, Madelaine
Ramanathan, Anita
Go, Ariel
Lawson, Erica J
Wang, Yaoming
Mack, William J
Thompson, Paul M
Schneider, Julie A
Varkey, Jobin
Langen, Ralf
Mullins, Eric
Jacobs, Russell E
Zlokovic, Berislav V
Тип документа:
Чланак у часопису (Објављена верзија)
,
© 2018 Nature America, Inc., part of Springer Nature
Метаподаци
Приказ свих података о документуАпстракт:
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.
Извор:
Nature Medicine, 2018, 24, 3, 326-337Финансирање / пројекти:
- US National Institute of Health grants NS100459, AG039452, NS034467 and AG023084
- Foundation Leducq Transatlantic Network of Excellence for the Study of Perivascular Spaces in Small Vessel Disease reference no. 16 CVD 05, and ES024936
DOI: 10.1038/nm.4482
ISSN: 1078-8956
PubMed: 29400711
WoS: 000426700900015
Scopus: 2-s2.0-85042940111
URI
http://www.nature.com/doifinder/10.1038/nm.4482http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=PMC5840035
https://radar.ibiss.bg.ac.rs/handle/123456789/3012