Age-related cognitive decline is associated with microbiota-gut-brain axis disorders and neuroinflammation in mice
Age-related cognitive decline is associated with microbiota-gut-brain axis disorders and neuroinflammation in mice
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DOI：
10.1016/j.bbr.2021.113125
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发表时间：
2021-01
影响因子：
2.7
通讯作者：
Mei-Ling Wu;Xueqin Yang;Li Xue;W. Duan;Jun-Rong Du
中科院分区：
文献类型：
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作者：
Mei-Ling Wu;Xueqin Yang;Li Xue;W. Duan;Jun-Rong Du
糖尿病相关的认知能力下降与慢性低度神经炎症有关，这可能是由许多因素之间的复杂相互作用引起的，例如中枢神经系统（CNS）和肠道微生物群之间的双向交流。本研究使用2月龄（年轻组）和15月龄（老年组）雄性C57 BL/6小鼠来探讨年龄相关的认知下降与微生物群-肠-脑轴障碍之间的潜在关联。我们观察到，与年轻小鼠相比，老年小鼠在学习记忆、神经元和突触功能方面表现出明显的缺陷。老年小鼠还表现出肠道微生物群的显著生态失调。还观察到肠屏障和血脑屏障的破坏，包括肠道、低度全身性和脑炎症的增加。老年小鼠血浆和脑内脂多糖（LPS）水平显著高于青年小鼠，肠和脑组织Toll样受体4（TLR 4）和髓样分化蛋白88（MyD 88）表达增加，核因子κB（NF-κB）核转位增加。这些发现表明，通过LPS诱导的TLR 4/NF-κB信号通路的激活而发生的微生物菌群-肠-脑轴功能障碍与年龄相关的神经炎症和认知能力下降有关。
Age-related cognitive decline is associated with chronic low grade neuroinflammation that may result from a complex interplay among many factors, such as bidirectional communication between the central nervous system (CNS) and gut microbiota. The present study used 2-month-old (young group) and 15-month-old (aged group) male C57BL/6 mice to explore the potential association between age-related cognitive decline and the microbiota-gut-brain axis disorder. We observed that aged mice exhibited significant deficits in learning and memory, neuronal and synaptic function compared with young mice. Aged mice also exhibited significant dysbiosis of the gut microbiota. Disruptions of the intestinal barrier and blood-brain barrier were also observed, including increases in intestinal, low-grade systemic and cerebral inflammation. Furthermore, plasma and brain levels of lipopolysaccharide (LPS) were significantly higher in aged mice compared with young mice, with increasing expression of Toll-like receptor 4 (TLR4) and myeloid differential protein-88 (MyD88) and the nuclear translocation of nuclear factor κB (NF-κB) in intestinal and brain tissues. These findings showed that microbiota-gut-brain axis dysfunction that occurs through LPS-induced activation of the TLR4/NF-κB signaling pathway is implicated in age-related neuroinflammation and cognitive decline.