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首页> 外文期刊>The journals of gerontology.Series A. Biological sciences and medical sciences >Obesity in Aging Exacerbates Blood-Brain Barrier Disruption, Neuroinflammation, and Oxidative Stress in the Mouse Hippocampus: Effects on Expression of Genes Involved in Beta-Amyloid Generation and Alzheimer's Disease
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Obesity in Aging Exacerbates Blood-Brain Barrier Disruption, Neuroinflammation, and Oxidative Stress in the Mouse Hippocampus: Effects on Expression of Genes Involved in Beta-Amyloid Generation and Alzheimer's Disease

机译：肥胖的衰老加剧了小鼠海马的血脑屏障破坏，神经炎症和氧化应激：对涉及β-淀粉样蛋白生成和阿尔茨海默氏病的基因表达的影响

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There is growing evidence that obesity has deleterious effects on the brain and cognitive function in the elderly population. However, the specific mechanisms through which aging and obesity interact to promote cognitive decline remain unclear. To test the hypothesis that aging exacerbates obesity-induced cerebromicrovascular damage and neuroinflammation, we compared young (7 months) and aged (24 months) high fat diet-fed obese C57BL/6 mice. Aging exacerbated obesity-induced systemic inflammation and blood-brain barrier disruption, as indicated by the increased circulating levels of proinflammatory cytokines and increased presence of extravasated immunoglobulin G in the hippocampus, respectively. Obesity-induced blood-brain barrier damage was associated with microglia activation, upregulation of activating Fc-gamma receptors and proinflammatory cytokines, and increased oxidative stress. Treatment of cultured primary microglia with sera derived from aged obese mice resulted in significantly more pronounced microglia activation and oxidative stress, as compared with treatment with young sera. Serum-induced activation and oxidative stress were also exacerbated in primary microglia derived from aged animals. Hippocampal expression of genes involved in regulation of the cellular amyloid precursor protein-dependent signaling pathways, beta-amyloid generation, and the pathogenesis of tauopathy were largely unaffected by obesity in aged mice. Collectively, obesity in aging is associated with a heightened state of systemic inflammation, which exacerbates blood-brain barrier disruption. The resulting neuroinflammation and oxidative stress in the mouse hippocampus likely contribute to the significant cognitive decline observed in aged obese animals.
机译：越来越多的证据表明，肥胖对老年人群的大脑和认知功能具有有害作用。但是，衰老和肥胖相互作用促进认知能力下降的具体机制仍不清楚。为了检验衰老加剧肥胖引起的脑微血管损伤和神经炎症的假说，我们比较了年轻（7个月）和年龄大（24个月）的高脂饮食喂养的肥胖C57BL / 6小鼠。衰老加剧了肥胖引起的全身性炎症和血脑屏障破坏，分别由促炎性细胞因子的循环水平增加和海马中外渗免疫球蛋白G的存在增加所表明。肥胖引起的血脑屏障损害与小胶质细胞激活，激活的Fc-γ受体和促炎性细胞因子的上调以及氧化应激增加有关。与用年轻血清治疗相比，用衍生自老年肥胖小鼠的血清处理培养的原发性小胶质细胞可显着增强小胶质细胞的活化和氧化应激。在源自老年动物的初级小胶质细胞中，血清诱导的活化和氧化应激也加剧了。在老年小鼠中，肥胖症对参与细胞淀粉样蛋白前体蛋白依赖性信号传导通路，β-淀粉样蛋白生成和tauopathy发病机理调控的基因的海马表达没有影响。总的来说，衰老中的肥胖与全身性炎症的加剧有关，这加剧了血脑屏障的破坏。小鼠海马体中产生的神经炎症和氧化应激可能会导致老年肥胖动物的认知能力明显下降。

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