Microglial metabolism is a pivotal factor in sexual dimorphism in Alzheimer's disease.
Microglial metabolism is a pivotal factor in sexual dimorphism in Alzheimer's disease.
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DOI：
10.1038/s42003-021-02259-y
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发表时间：
2021-06-10
影响因子：
5.9
通讯作者：
Lynch MA
中科院分区：
文献类型：
--
作者：
Guillot-Sestier MV;Araiz AR;Mela V;Gaban AS;O'Neill E;Joshi L;Chouchani ET;Mills EL;Lynch MA
年龄和性别是阿尔茨海默病（AD）的主要危险因素，女性发病率较高。神经炎症是AD的标志，有助于疾病的发病机制，并且与不适当的小胶质细胞活化和神经退行性变有着不可分割的联系。我们研究了APP/PS1小鼠和AD患者死后组织中小胶质细胞的性别相关差异。指示小胶质细胞活化的基因变化在雌性APP/PS1小鼠的细胞中优先增加，雄性和雌性的细胞在形态、代谢和功能上不同。来自雌性APP/PS1小鼠的小胶质细胞是糖酵解的，吞噬细胞较少，并且与淀粉样变性增加相关，而来自雄性的小胶质细胞是变形虫样的，这也是来自雄性AD患者的死后组织的情况，其中斑块负荷减少。我们认为，小胶质细胞的性别相关差异可能解释，至少在一定程度上，在AD的性别二型性。Guillot-Sestier等人研究了阿尔茨海默病（AD）患者死后脑组织以及APP/PS1 AD小鼠模型中小胶质细胞的性别相关差异。他们证明，在雄性和雌性AD小鼠之间存在与小胶质细胞活化和代谢相关的基因的差异表达，以及在患者死后组织中也明显存在的形态学差异，因此有助于我们理解AD的性二态性。
Age and sex are major risk factors in Alzheimer’s disease (AD) with a higher incidence of the disease in females. Neuroinflammation, which is a hallmark of AD, contributes to disease pathogenesis and is inexorably linked with inappropriate microglial activation and neurodegeneration. We investigated sex-related differences in microglia in APP/PS1 mice and in post-mortem tissue from AD patients. Changes in genes that are indicative of microglial activation were preferentially increased in cells from female APP/PS1 mice and cells from males and females were morphological, metabolically and functionally distinct. Microglia from female APP/PS1 mice were glycolytic and less phagocytic and associated with increased amyloidosis whereas microglia from males were amoeboid and this was also the case in post-mortem tissue from male AD patients, where plaque load was reduced. We propose that the sex-related differences in microglia are likely to explain, at least in part, the sexual dimorphism in AD. Guillot-Sestier et al investigated sex-related differences in microglia in postmortem brain tissue from Alzheimer’s Disease (AD) patients as well as in the APP/PS1 AD mouse model. They demonstrated that there was differential expression of genes associated with microglial activation and metabolism between male and female AD mice as well as differences in morphology that were also apparent in the patient post-mortem tissue, which therefore contributes to our understanding of sexual dimorphism in AD.
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影响因子：
5.3
作者：
Karperien A;Ahammer H;Jelinek HF
通讯作者：
Jelinek HF
影响因子：
5.1
作者：
Fu, Ruying;Shen, Qingyu;Xu, Pengfei;Luo, Jin Jun;Tang, Yamei
通讯作者：
Tang, Yamei
DOI：
10.1073/pnas.0403535101
发表时间：
2004-11-02
影响因子：
11.1
作者：
Li, Y;Nowotny, P;Grupe, A
通讯作者：
Grupe, A
影响因子：
64.8
作者：
Mills EL;Pierce KA;Jedrychowski MP;Garrity R;Winther S;Vidoni S;Yoneshiro T;Spinelli JB;Lu GZ;Kazak L;Banks AS;Haigis MC;Kajimura S;Murphy MP;Gygi SP;Clish CB;Chouchani ET
通讯作者：
Chouchani ET
影响因子：
32.4
作者：
Hammond, Timothy R.;Dufort, Connor;Stevens, Beth
通讯作者：
Stevens, Beth