斯坦福大学医学院Tony Wyss-Coray小组在研究中取得进展。他们提出了老化的血液破坏海马神经前体活动，并通过脑内皮细胞VCAM1激活小胶质细胞。2019年出版的《Nature Medicine》发表了这项成果。

该课题组研究人员假设脑内皮细胞（BEC）至少能介导这个过程中的一些效应。他们观察到老年小鼠海马中的BEC能表达炎症转录谱，并局部上调血管细胞粘附分子1（VCAM1），一种促进血管和免疫细胞相互作用的蛋白质。同时，老年人和小鼠血浆中shed,可溶的VCAM1水平显著增加，其血浆足以增加体外培养的BEC和幼鼠海马中VCAM1的表达。全身性地注射抗VCAM1抗体或敲除BECs中的Vcam1基因可抵消老年的血浆对年轻大脑的不利影响，并逆转老年小鼠大脑的衰老方面，包括小胶质细胞的激活和认知缺陷。这些发现证实，血脑屏障处的脑内皮细胞的VCAM1可能成为治疗年龄相关的神经退行性疾病的靶点。

据悉，老化的循环环境能够激活小胶质细胞，降低神经前体细胞活性并损害小鼠的认知能力。

附：英文原文

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

Author: Hanadie Yousef, Cathrin J. Czupalla, Davis Lee, Michelle B. Chen, Ashley N. Burke, Kristy A. Zera, Judith Zandstra, Elisabeth Berber, Benoit Lehallier, Vidhu Mathur, Ramesh V. Nair, Liana N. Bonanno, Andrew C. Yang, Todd Peterson, Husein Hadeiba, Taylor Merkel, Jakob Krbelin, Markus Schwaninger, Marion S. Buckwalter, Stephen R. Quake, Eugene C. Butcher, Tony Wyss-Coray

Issue&Volume: Volume 25 Issue 6，June 2019

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 vascularimmune 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 bloodbrain barrier as a possible target to treat age-related neurodegeneration.

DOI: 10.1038/s41591-019-0440-4

Source:https://www.nature.com/articles/s41591-019-0440-4