Microglial TREM2 Mitigates Inflammatory Responses and Neuronal Apoptosis in Angiotensin II-Induced Hypertension in Middle-Aged Mice.
Microglial TREM2 Mitigates Inflammatory Responses and Neuronal Apoptosis in Angiotensin II-Induced Hypertension in Middle-Aged Mice.
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小胶质细胞 TREM2 减轻血管紧张素 II 诱导的中年小鼠高血压的炎症反应和神经元凋亡
DOI：
10.3389/fnagi.2021.716917
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发表时间：
2021
影响因子：
4.8
通讯作者：
Hao J
中科院分区：
文献类型：
--
作者：
Xu X;Du L;Jiang J;Yang M;Wang Z;Wang Y;Tang T;Fu X;Hao J
越来越多的证据表明，高血压和衰老是通过诱导神经炎症发展为迟发性阿尔茨海默病（LOAD）的突出危险因素。最近的研究表明，通过活化的小胶质细胞的神经炎症诱导反应性星形胶质细胞，称为A1星形胶质细胞，高度上调许多经典的补体级联基因，这些基因在神经退行性疾病中对神经元具有破坏性。此外，髓样细胞上表达的触发受体2（TREM2）被认为是最强的单等位基因遗传危险因素之一，并在LOAD的神经炎症中起重要作用。然而，小胶质细胞在A1星形胶质细胞活化中的调节机制仍不清楚。我们在中年小鼠中引入了血管紧张素II诱导的高血压，并发现高血压上调的TREM2表达和A1星形胶质细胞活化参与了本研究中使用的动物模型的神经炎症。体外实验结果表明，小胶质细胞TREM2的过表达不仅减轻了小胶质细胞的炎症反应，而且对逆转A1星形胶质细胞活化和神经元毒性具有有益的作用。
Growing evidence suggests that hypertension and aging are prominent risk factors for the development of late-onset Alzheimer’s disease (LOAD) by inducement of neuroinflammation. Recent study showed that neuroinflammation via activated microglia induces reactive astrocytes, termed A1 astrocytes, that highly upregulate numerous classical complement cascade genes that are destructive to neurons in neurodegeneration diseases. Moreover, triggering receptor expressed on myeloid cells 2 (TREM2) is considered as one of the strongest single-allele genetic risk factors and plays important roles in neuroinflammation for LOAD. However, the mechanisms of microglia in the regulation of A1 astrocytic activation are still not clear. We introduced angiotensin II-induced hypertension in middle-aged mice and found that hypertension-upregulated TREM2 expression and A1 astrocytic activation were involved in neuroinflammation in the animal models used in this study. The in vitro results revealed that overexpression of microglial TREM2 not only mitigated microglial inflammatory response but also had salutary effects on reverse A1 astrocytic activation and neuronal toxicity.
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星形胶质细胞诱导的突触发生的分子机制。
影响因子：
5.7
作者：
Baldwin KT;Eroglu C
通讯作者：
Eroglu C
DOI：
10.1084/jem.20142322
发表时间：
2015-03-09
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Jay TR;Miller CM;Cheng PJ;Graham LC;Bemiller S;Broihier ML;Xu G;Margevicius D;Karlo JC;Sousa GL;Cotleur AC;Butovsky O;Bekris L;Staugaitis SM;Leverenz JB;Pimplikar SW;Landreth GE;Howell GR;Ransohoff RM;Lamb BT
通讯作者：
Lamb BT
影响因子：
4.2
作者：
Carnevale, Daniela;Mascio, Giada;Minghetti, Luisa
通讯作者：
Minghetti, Luisa
DOI：
10.1152/ajpheart.00247.2015
发表时间：
2016-02-01
影响因子：
4.8
作者：
Biancardi, Vinicia Campana;Stranahan, Alexis M.;Stern, Javier E.
通讯作者：
Stern, Javier E.
影响因子：
4.2
作者：
Gentile, Maria Teresa;Poulet, Roberta;Lembo, Giuseppe
通讯作者：
Lembo, Giuseppe