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Aged blood impairs hippocampal neural precursor activity and activates microglia via brain endothelial cell VCAM1

Nature medicine, 2019-06, Vol.25 (6), p.988-1000 [Peer Reviewed Journal]

COPYRIGHT 2019 Nature Publishing Group ;COPYRIGHT 2019 Nature Publishing Group ;The Author(s), under exclusive licence to Springer Nature America, Inc. 2019. ;ISSN: 1078-8956 ;EISSN: 1546-170X ;DOI: 10.1038/s41591-019-0440-4 ;PMID: 31086348

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Title:
Aged blood impairs hippocampal neural precursor activity and activates microglia via brain endothelial cell VCAM1
Author: Yousef, Hanadie ; Czupalla, Cathrin J ; Lee, Davis ; Chen, Michelle B ; Burke, Ashley N ; Zera, Kristy A ; Zandstra, Judith ; Berber, Elisabeth ; Lehallier, Benoit ; Mathur, Vidhu ; Nair, Ramesh V ; Bonanno, Liana N ; Yang, Andrew C ; Peterson, Todd ; Hadeiba, Husein ; Merkel, Taylor ; Körbelin, Jakob ; Schwaninger, Markus ; Buckwalter, Marion S ; Quake, Stephen R ; Butcher, Eugene C ; Wyss-Coray, Tony
Subjects: Ablation ; Adolescent ; Adult ; Aged ; Aging ; Aging - blood ; Aging - immunology ; Aging - metabolism ; Animals ; Antibodies ; Blood ; Blood-brain barrier ; Blood-Brain Barrier - immunology ; Blood-Brain Barrier - metabolism ; Brain ; Brain - cytology ; Brain - metabolism ; Cell adhesion ; Cell adhesion & migration ; Cell adhesion molecules ; Cell interactions ; Cells, Cultured ; Cognition ; Cognitive ability ; Endothelial cells ; Endothelial Cells - metabolism ; Endothelium ; Female ; Gene Deletion ; Health aspects ; Hippocampus ; Hippocampus (Brain) ; Hippocampus - cytology ; Hippocampus - metabolism ; Humans ; Immune system ; Inflammation ; Inflammation Mediators - metabolism ; Male ; Mice ; Mice, Inbred NOD ; Mice, Knockout ; Mice, SCID ; Microglia ; Microglia - metabolism ; Neural circuitry ; Neural Stem Cells - cytology ; Neural Stem Cells - metabolism ; Neurodegeneration ; Physiological aspects ; Precursors ; Transcription ; Vascular cell adhesion molecule 1 ; Vascular Cell Adhesion Molecule-1 - blood ; Vascular Cell Adhesion Molecule-1 - genetics ; Vascular Cell Adhesion Molecule-1 - metabolism ; Young Adult
Is Part Of: Nature medicine, 2019-06, Vol.25 (6), p.988-1000
Description: 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.
Publisher: United States: Nature Publishing Group
Language: English
Identifier: ISSN: 1078-8956
EISSN: 1546-170X
DOI: 10.1038/s41591-019-0440-4
PMID: 31086348
Source: AUTh Library subscriptions: ProQuest Central
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Aged blood impairs hippocampal neural precursor activity and activates microglia via brain endothelial cell VCAM1

COPYRIGHT 2019 Nature Publishing Group ;COPYRIGHT 2019 Nature Publishing Group ;The Author(s), under exclusive licence to Springer Nature America, Inc. 2019. ;ISSN: 1078-8956 ;EISSN: 1546-170X ;DOI: 10.1038/s41591-019-0440-4 ;PMID: 31086348

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