Aging-induced type I interferon response at the choroid plexus negatively affects brain function

被引：475

作者：

Baruch, Kuti ^{[1
]}

Deczkowska, Aleksandra ^{[1
]}

David, Eyal ^{[2
]}

Castellano, Joseph M. ^{[3
]}

Miller, Omer ^{[1
]}

Kertser, Alexander ^{[1
]}

Berkutzki, Tamara ^{[1
]}

Barnett-Itzhaki, Zohar ^{[2
]}

Bezalel, Dana ^{[2
]}

Wyss-Coray, Tony ^{[3
]}

Amit, Ido ^{[2
]}

Schwartz, Michal ^{[1
]}

机构：

[1] Weizmann Inst Sci, Dept Neurobiol, IL-76100 Rehovot, Israel

[2] Weizmann Inst Sci, Dept Immunol, IL-76100 Rehovot, Israel

[3] Stanford Univ, Sch Med, Dept Neurol & Neurol Sci, Stanford, CA 94305 USA

来源：

SCIENCE | 2014年 / 346卷 / 6205期

基金：

欧洲研究理事会;

关键词：

ADULT HIPPOCAMPAL NEUROGENESIS; PERSISTENT LCMV INFECTION; CENTRAL-NERVOUS-SYSTEM; IMMUNE SURVEILLANCE; COGNITIVE FUNCTION; T-CELLS; BLOCKADE; REJUVENATION; INFLAMMATION; RECRUITMENT;

D O I：

10.1126/science.1252945

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

070301 [无机化学]; 070403 [天体物理学]; 070507 [自然资源与国土空间规划学]; 090105 [作物生产系统与生态工程];

摘要：

Aging-associated cognitive decline is affected by factors produced inside and outside the brain. By using multiorgan genome-wide analysis of aged mice, we found that the choroid plexus, an interface between the brain and the circulation, shows a type I interferon (IFN-I)-dependent gene expression profile that was also found in aged human brains. In aged mice, this response was induced by brain-derived signals, present in the cerebrospinal fluid. Blocking IFN-I signaling within the aged brain partially restored cognitive function and hippocampal neurogenesis and reestablished IFN-II-dependent choroid plexus activity, which is lost in aging. Our data identify a chronic aging-induced IFN-I signature, often associated with antiviral response, at the brain's choroid plexus and demonstrate its negative influence on brain function, thereby suggesting a target for ameliorating cognitive decline in aging.

引用

页码：89 / 93

页数：5

共 30 条

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