Microglial phenotypes in the human epileptic temporal lobe.
Microglial phenotypes in the human epileptic temporal lobe.
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DOI：
10.1093/brain/awy276
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发表时间：
2018-12-01
期刊：
影响因子：
--
通讯作者：
Miles R
中科院分区：
文献类型：
--
作者：
Morin-Brureau M;Milior G;Royer J;Chali F;Le Duigou C;Savary E;Blugeon C;Jourdren L;Akbar D;Dupont S;Navarro V;Baulac M;Bielle F;Mathon B;Clemenceau S;Miles R
小胶质细胞是大脑的免疫细胞，具有高度可塑性，并具有多种功能表型。癫痫人脑不同区域和不同状态的表型差异研究甚少。在这里，我们使用转录组学，解剖学，活细胞成像和细胞因子释放的ELISA测量检查颞叶癫痫患者的小胶质细胞。探索了两种不同的小胶质细胞表型。首先，我们询问了在同一大脑中高和低神经元损失区域之间小胶质细胞表型的差异。其次，我们询问了最近的癫痫发作如何改变小胶质细胞表型。在神经元较少的皮层区域，小胶质细胞具有变形虫状而不是分枝状的形状，表达激活标记物，并且对嘌呤能刺激反应更快。修复性白细胞介素（IL-10）调节CA 1和CA 3区域小胶质细胞的基础表型，导致神经元丢失和神经胶质增生。为了了解癫痫发作诱导的表型变化，我们估计了从最后一次癫痫发作到组织收集的延迟，这些延迟来自立即早期基因转录物读数的变化。通过与红藻氨酸盐处理小鼠的结果进行比较，验证了该数据的伪时间排序。它揭示了一种局部和短暂的表型，其中小胶质细胞分泌人白细胞介素CXCL 8，IL-1B和其他细胞因子。这种分泌反应部分通过NRLP 3炎性体介导。
Microglia, immune cells of the brain, are highly plastic and possess multiple functional phenotypes. Differences in phenotype in different regions and different states of epileptic human brain have been little studied. Here we use transcriptomics, anatomy, imaging of living cells and ELISA measurements of cytokine release to examine microglia from patients with temporal lobe epilepsies. Two distinct microglial phenotypes were explored. First we asked how microglial phenotype differs between regions of high and low neuronal loss in the same brain. Secondly we asked how microglial phenotype is changed by a recent seizure. In sclerotic areas with few neurons, microglia have an amoeboid rather than ramified shape, express activation markers and respond faster to purinergic stimuli. The repairing interleukin, IL-10, regulates the basal phenotype of microglia in the CA1 and CA3 regions with neuronal loss and gliosis. To understand changes in phenotype induced by a seizure, we estimated the delay from the last seizure until tissue collection from changes in reads for immediate early gene transcripts. Pseudotime ordering of this data was validated by comparison with results from kainate-treated mice. It revealed a local and transient phenotype in which microglia secrete the human interleukin CXCL8, IL-1B and other cytokines. This secretory response is mediated in part via the NRLP3 inflammasome.
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影响因子：
25
作者：
Galatro, Thais F.;Holtman, Inge R.;Eggen, Bart J. L.
通讯作者：
Eggen, Bart J. L.
影响因子：
5.6
作者：
Aronica E;Bauer S;Bozzi Y;Caleo M;Dingledine R;Gorter JA;Henshall DC;Kaufer D;Koh S;Löscher W;Louboutin JP;Mishto M;Norwood BA;Palma E;Poulter MO;Terrone G;Vezzani A;Kaminski RM
通讯作者：
Kaminski RM
影响因子：
3.7
作者：
Choi, Su-Lim;Lee, Sang Jun;Lee, Seung-Goo
通讯作者：
Lee, Seung-Goo
DOI：
10.4049/jimmunol.0802367
发表时间：
2009-03-01
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Bryan NB;Dorfleutner A;Rojanasakul Y;Stehlik C
通讯作者：
Stehlik C
影响因子：
3.7
作者：
Charolidi N;Schilling T;Eder C
通讯作者：
Eder C