Aging. Aging-induced type I interferon response at the choroid plexus negatively affects brain function.
Aging. Aging-induced type I interferon response at the choroid plexus negatively affects brain function.
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DOI：
10.1126/science.1252945
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发表时间：
2014-10-03
期刊：
影响因子：
--
通讯作者：
Schwartz M
中科院分区：
文献类型：
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作者：
Baruch K;Deczkowska A;David E;Castellano JM;Miller O;Kertser A;Berkutzki T;Barnett-Itzhaki Z;Bezalel D;Wyss-Coray T;Amit I;Schwartz M
与年龄相关的认知能力下降受到大脑内外产生的因素的影响。我们在老年小鼠和人类中发现，脉络丛（CP）是大脑和循环系统之间的上皮界面，显示出 I 型干扰素（IFN-I）依赖性表达谱，通常与抗病毒反应相关。这种特征是由老年小鼠脑脊液中存在的脑源信号诱导的。使用 IFN-I 受体中和抗体阻断认知受损的老年小鼠大脑内的 IFN-I 信号传导，导致认知功能和海马神经发生部分恢复，并重新建立因衰老而丧失的 IFN-II 依赖性 CP 活性。我们的数据确定了 CP 处衰老诱导的 IFN-I 特征，并证明了其对大脑功能的负面影响，从而表明了治疗干预与年龄相关的认知衰退的潜在目标。
Age-associated cognitive decline is affected by factors produced inside and outside the brain. We found in aged mice and humans, that the choroid plexus (CP), an epithelial interface between the brain and the circulation, shows a type I interferon (IFN-I)-dependent expression profile, often associated with anti-viral responses. This signature was induced by brain-derived signals present in the cerebrospinal fluid of aged mice. Blocking IFN-I signaling within the brain of cognitively-impaired aged mice, using IFN-I receptor neutralizing antibody, led to partial restoration of cognitive function and hippocampal neurogenesis, and reestablished IFN-II-dependent CP activity, lost in aging. Our data identify an aging-induced IFN-I signature at the CP, and demonstrate its negative influence on brain function, thereby suggesting a potential target for therapeutic intervention for age-related cognitive decline.