| Literature DB >> 31086348 |
Hanadie Yousef1,2, Cathrin J Czupalla2,3,4, Davis Lee1,2, Michelle B Chen5, Ashley N Burke1,2, Kristy A Zera1, Judith Zandstra1,2, Elisabeth Berber1,2, Benoit Lehallier1,2, Vidhu Mathur1,2, Ramesh V Nair6, Liana N Bonanno1,2, Andrew C Yang1,5, Todd Peterson1, Husein Hadeiba3,4, Taylor Merkel1,2, Jakob Körbelin7, Markus Schwaninger8, Marion S Buckwalter1,9, Stephen R Quake5,10, Eugene C Butcher2,3,4, Tony Wyss-Coray11,12,13,14.
Abstract
An aged circulatory environment can activate microglia, reduce neural precursor cell activity and impair cognition in mice. We hypothesized that brain endothelial cells (BECs) mediate at least some of these effects. We observe that BECs in the aged mouse hippocampus express an inflammatory transcriptional profile with focal upregulation of vascular cell adhesion molecule 1 (VCAM1), a protein that facilitates vascular-immune cell interactions. Concomitantly, levels of the shed, soluble form of VCAM1 are prominently increased in the plasma of aged humans and mice, and their plasma is sufficient to increase VCAM1 expression in cultured BECs and the hippocampi of young mice. Systemic administration of anti-VCAM1 antibody or genetic ablation of Vcam1 in BECs counteracts the detrimental effects of plasma from aged individuals on young brains and reverses aging aspects, including microglial reactivity and cognitive deficits, in the brains of aged mice. Together, these findings establish brain endothelial VCAM1 at the blood-brain barrier as a possible target to treat age-related neurodegeneration.Entities:
Mesh：
Substances：
Year: 2019 PMID： 31086348 PMCID： PMC6642642 DOI： 10.1038/s41591-019-0440-4
Source DB: PubMed Journal: Nat Med ISSN： 1078-8956 Impact factor: 53.440