N-acetylneuraminic acid links immune exhaustion and accelerated memory deficit in diet-induced obese Alzheimer's disease mouse model.
N-acetylneuraminic acid links immune exhaustion and accelerated memory deficit in diet-induced obese Alzheimer's disease mouse model.
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DOI：
10.1038/s41467-023-36759-8
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发表时间：
2023-03-09
影响因子：
16.6
通讯作者：
Schwartz, Michal
中科院分区：
文献类型：
--
作者：
Suzzi, Stefano;Croese, Tommaso;Ravid, Adi;Gold, Or;Clark, Abbe R.;Medina, Sedi;Kitsberg, Daniel;Adam, Miriam;Vernon, Katherine A.;Kohnert, Eva;Shapira, Inbar;Malitsky, Sergey;Itkin, Maxim;Brandis, Alexander;Mehlman, Tevie;Salame, Tomer M.;Colaiuta, Sarah P.;Cahalon, Liora;Slyper, Michal;Greka, Anna;Habib, Naomi;Schwartz, Michal
全身免疫支持终身大脑功能。肥胖对全身免疫造成慢性负担。另外，肥胖被证明是阿尔茨海默病（AD）的一个危险因素。本研究表明，高脂肪致肥性饮食加速了AD小鼠模型（5xFAD）的识别记忆障碍。在肥胖5xFAD小鼠中，海马细胞仅表现出轻微的饮食相关转录变化，而脾脏免疫景观表现出类似衰老的CD4+ t细胞失调。通过血浆代谢物分析，我们确定了游离n-乙酰神经氨酸（NANA），主要的唾液酸，作为小鼠识别记忆障碍与脾免疫抑制细胞增加之间的代谢物。单核rna测序显示小鼠内脏脂肪巨噬细胞是NANA的潜在来源。在体外，NANA降低了小鼠和人体内CD4+ t细胞的增殖。在体内，给标准饮食小鼠服用NANA重现了高脂肪饮食对5xFAD小鼠CD4+ T细胞的影响，并加速了识别记忆障碍。我们认为肥胖通过全身免疫衰竭加速了AD小鼠模型的疾病表现。肥胖和衰老增加阿尔茨海默病（AD）的风险。本研究通过使用AD小鼠模型和高脂肪饮食，我们认为免疫衰竭与这两种危险因素有关，并确定了一种能加速免疫功能障碍和记忆缺陷的代谢物。
Systemic immunity supports lifelong brain function. Obesity posits a chronic burden on systemic immunity. Independently, obesity was shown as a risk factor for Alzheimer’s disease (AD). Here we show that high-fat obesogenic diet accelerated recognition-memory impairment in an AD mouse model (5xFAD). In obese 5xFAD mice, hippocampal cells displayed only minor diet-related transcriptional changes, whereas the splenic immune landscape exhibited aging-like CD4+ T-cell deregulation. Following plasma metabolite profiling, we identified free N-acetylneuraminic acid (NANA), the predominant sialic acid, as the metabolite linking recognition-memory impairment to increased splenic immune-suppressive cells in mice. Single-nucleus RNA-sequencing revealed mouse visceral adipose macrophages as a potential source of NANA. In vitro, NANA reduced CD4+ T-cell proliferation, tested in both mouse and human. In vivo, NANA administration to standard diet-fed mice recapitulated high-fat diet effects on CD4+ T cells and accelerated recognition-memory impairment in 5xFAD mice. We suggest that obesity accelerates disease manifestation in a mouse model of AD via systemic immune exhaustion. Obesity and aging increase Alzheimer’s disease (AD) risk. Here, using an AD mouse model and high-fat diet, we suggest that immune exhaustion links the two risk factors, and identify a metabolite that can hasten immune dysfunction and memory deficit.
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脑膜免疫调节学习和记忆：IL-4 的关键作用。
影响因子：
15.3
作者：
Derecki, Noel C.;Cardani, Amber N.;Yang, Chun Hui;Quinnies, Kayla M.;Crihfield, Anastasia;Lynch, Kevin R.;Kipnis, Jonathan
通讯作者：
Kipnis, Jonathan
影响因子：
--
作者：
Baek H;Ye M;Kang GH;Lee C;Lee G;Choi DB;Jung J;Kim H;Lee S;Kim JS;Lee HJ;Shim I;Lee JH;Bae H
通讯作者：
Bae H
DOI：
10.1093/bioinformatics/btu638
发表时间：
2015-01-15
期刊：
Bioinformatics (Oxford, England)
影响因子：
--
作者：
Anders S;Pyl PT;Huber W
通讯作者：
Huber W
影响因子：
82.9
作者：
Baruch, Kuti;Deczkowska, Aleksandra;Schwartz, Michal
通讯作者：
Schwartz, Michal
影响因子：
3
作者：
Amith, Schammim Ray;Jayanth, Preethi;Szewczuk, Myron R.
通讯作者：
Szewczuk, Myron R.