Aged blood inhibits hippocampal neurogenesis and activates microglia through VCAM1 at the blood-brain barrier
By
Hanadie Yousef,
Cathrin J Czupalla,
Davis Lee,
Ashley Burke,
Michelle Chen,
Judith Zandstra,
Elisabeth Berber,
Benoit Lehallier,
Vidhu Mathur,
Ramesh V Nair,
Liana Bonanno,
Taylor Merkel,
Markus Schwaninger,
Stephen Quake,
Eugene C Butcher,
Tony Wyss-Coray
Posted 03 Jan 2018
bioRxiv DOI: 10.1101/242198
An aged circulatory environment can promote brain dysfunction and we hypothesized that the blood-brain barrier (BBB) mediates at least some of these effects. We observe brain endothelial cells (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, the shed, soluble form of VCAM1 is prominently increased in the aged circulation of humans and mice, and aged plasma is sufficient to increase VCAM1 expression in cultured BECs and young mouse hippocampi. Systemic anti-VCAM1 antibody or genetic ablation of VCAM1 in BECs counteracts the detrimental effects of aged plasma on young brains and reverses aging aspects in old mouse brains. Thus, VCAM1 is a negative regulator of adult neurogenesis and inducer of microglial reactivity, establishing VCAM1 and the luminal side of the BBB as possible targets to treat age-related neurodegeneration.
Download data
- Downloaded 5,378 times
- Download rankings, all-time:
- Site-wide: 2,875
- In neuroscience: 144
- Year to date:
- Site-wide: 41,945
- Since beginning of last month:
- Site-wide: 38,291
Altmetric data
Downloads over time
Distribution of downloads per paper, site-wide
PanLingua
News
- 27 Nov 2020: The website and API now include results pulled from medRxiv as well as bioRxiv.
- 18 Dec 2019: We're pleased to announce PanLingua, a new tool that enables you to search for machine-translated bioRxiv preprints using more than 100 different languages.
- 21 May 2019: PLOS Biology has published a community page about Rxivist.org and its design.
- 10 May 2019: The paper analyzing the Rxivist dataset has been published at eLife.
- 1 Mar 2019: We now have summary statistics about bioRxiv downloads and submissions.
- 8 Feb 2019: Data from Altmetric is now available on the Rxivist details page for every preprint. Look for the "donut" under the download metrics.
- 30 Jan 2019: preLights has featured the Rxivist preprint and written about our findings.
- 22 Jan 2019: Nature just published an article about Rxivist and our data.
- 13 Jan 2019: The Rxivist preprint is live!