Astrocytes Excessively Engulf Synapses in a Mouse Model of Alzheimer's Disease.
Astrocytes Excessively Engulf Synapses in a Mouse Model of Alzheimer's Disease.
复制标题
阿尔茨海默病小鼠模型中的星形胶质细胞过度吞噬突触。
DOI：
10.3390/ijms25021160
复制
发表时间：
2024-01-18
影响因子：
5.6
通讯作者：
中科院分区：
文献类型：
--
作者：
突触丢失是阿尔茨海默病（AD）最重要的特征之一，并与认知能力下降相关。星形胶质细胞通过多个EGF样结构域10（MEGF 10）通路介导发育和成人大脑中的突触消除，以建立精确的神经连接。然而，星形胶质细胞是否以及如何介导AD中的突触丢失仍然未知。我们在这里发现，星形胶质细胞的吞噬受体MEGF 10在体内和体外显著增加，这导致APP/PS1小鼠中星形胶质细胞对突触的过度吞噬。我们还观察到APP/PS1小鼠的星形胶质细胞溶酶体相关膜蛋白1（LAMP 1）显著升高，与吞噬的突触点共定位，APP/PS1小鼠的星形胶质细胞溶酶体相对于野生型小鼠含有更多的吞噬的突触点。总之，我们的数据提供的证据表明，星形胶质细胞过度吞噬突触APP/PS1小鼠，这是由增加MEGF 10和激活的溶酶体介导的。以星形胶质细胞突触吞噬通路为靶点的治疗方法有望成为AD的有效治疗手段。
Synapse loss is one of the most critical features in Alzheimer’s disease (AD) and correlates with cognitive decline. Astrocytes mediate synapse elimination through multiple EGF-like domains 10 (MEGF10) pathways in the developing and adult brain to build the precise neural connectivity. However, whether and how astrocytes mediate synapse loss in AD remains unknown. We here find that the phagocytic receptor MEGF10 of astrocytes is significantly increased in vivo and in vitro, which results in excessive engulfment of synapses by astrocytes in APP/PS1 mice. We also observe that the astrocytic lysosomal-associated membrane protein 1 (LAMP1) is significantly elevated, colocalized with the engulfed synaptic puncta in APP/PS1 mice, and astrocytic lysosomes contain more engulfed synaptic puncta in APP/PS1 mice relative to wild type mice. Together, our data provide evidence that astrocytes excessively engulf synapses in APP/PS1 mice, which is mediated by increased MEGF10 and activated lysosomes. The approach targeting synapse engulfment pathway in astrocytes would be a potent therapy for AD.
登录
查看更多内容
影响因子：
34.7
作者：
Clarke, Laura E.;Barres, Ben A.
通讯作者：
Barres, Ben A.
影响因子：
16.2
作者：
Paolicelli RC;Jawaid A;Henstridge CM;Valeri A;Merlini M;Robinson JL;Lee EB;Rose J;Appel S;Lee VM;Trojanowski JQ;Spires-Jones T;Schulz PE;Rajendran L
通讯作者：
Rajendran L
DOI：
10.1038/s41572-021-00269-y
发表时间：
2021-05-13
期刊：
Nature reviews. Disease primers
影响因子：
--
作者：
Knopman DS;Amieva H;Petersen RC;Chételat G;Holtzman DM;Hyman BT;Nixon RA;Jones DT
通讯作者：
Jones DT
影响因子：
25
作者：
Lee, Ju-Hyun;Yang, Dun-Sheng;Goulbourne, Chris N.;Im, Eunju;Stavrides, Philip;Pensalfini, Anna;Chan, Han;Bouchet-Marquis, Cedric;Bleiwas, Cynthia;Berg, Martin J.;Huo, Chunfeng;Peddy, James;Pawlik, Monika;Levy, Efrat;Rao, Mala;Staufenbiel, Mathias;Nixon, Ralph A.
通讯作者：
Nixon, Ralph A.
影响因子：
3.7
作者：
Jung YJ;Chung WS
通讯作者：
Chung WS