Targeting CCL5 signaling attenuates neuroinflammation after seizure.
Targeting CCL5 signaling attenuates neuroinflammation after seizure.
复制标题
DOI：
10.1111/cns.14006
复制
发表时间：
2023-01
影响因子：
5.5
通讯作者：
中科院分区：
文献类型：
--
作者：
癫痫是一种神经系统疾病，会导致无端的反复发作。临床和实验研究积累的证据表明，神经炎症会加剧癫痫发作。我们使用 10× Genomics 空间转录组学研究了癫痫小鼠模型特定脑区中发生的转录变化。应用差异基因表达和通路分析来研究癫痫发作的潜在信号靶标，包括 CCL5/CCR5 通路。 Maraviroc 是 FDA 批准的 C-C 趋化因子受体 5 (CCR5) 拮抗剂，用于验证 CCL5/CCR5 信号传导对癫痫小鼠的影响。我们在癫痫小鼠的海马体中发现了显着的区域转录组特征。癫痫小鼠的海马体表现出独特的炎症基因特征，包括神经胶质细胞激活、细胞凋亡和免疫反应。特别是，我们观察到 C-C 趋化因子配体 5 (CCL5) 在整个癫痫发作海马体中显着表达。通过马拉韦罗阻断 CCL5/CCR5 信号传导可防止癫痫小鼠的小胶质细胞激活和神经元变性。这项研究支持 CCL5/CCR5 信号传导针对癫痫发作后神经炎症的潜力。空间转录组显示癫痫发作小鼠模型海马中CCL5的表达水平显着升高。在马拉韦罗治疗下，观察到癫痫行为、神经元变性和胶质细胞活化的减少，并且癫痫小鼠的存活率提高。
Epilepsy is a neurological condition that causes unprovoked, recurrent seizures. Accumulating evidence from clinical and experimental studies indicates that neuroinflammation exacerbates seizure activity. We investigated the transcriptional changes occurring in specific brain domains of a seizure mouse model, using 10× Genomics spatial transcriptomics. Differential gene expression and pathway analysis were applied to investigate potential signaling targets for seizure, including CCL5/CCR5 pathway. Maraviroc, an FDA‐approved C‐C chemokine receptor 5 (CCR5) antagonist, was used to verify the impact of CCL5/CCR5 signaling in seizure mice. We found distinguished regional transcriptome features in the hippocampus of seizure mice. The hippocampus exhibited unique inflammatory gene signatures, including glia activation, apoptosis, and immune response in seizure mice. Especially, we observed notable expression of C‐C chemokine ligand 5 (CCL5) throughout the entire seizure hippocampus. Blockade of CCL5/CCR5 signaling via maraviroc prevented microglia activation and neuron degeneration in seizure mice. This study supports the potential of CCL5/CCR5 signaling for targeting neuroinflammation after seizure. The spatial transcriptome demonstrated that the expression level of CCL5 in the hippocampus of seizure mice model was significantly increased. Under the treatment of maraviroc, the reduction of seizure behavior, neuronal degeneration, and glial cell activation were observed, and the survival rate of seizure mice was improved.
登录
查看更多内容
影响因子：
25
作者：
Maynard KR;Collado-Torres L;Weber LM;Uytingco C;Barry BK;Williams SR;Catallini JL 2nd;Tran MN;Besich Z;Tippani M;Chew J;Yin Y;Kleinman JE;Hyde TM;Rao N;Hicks SC;Martinowich K;Jaffe AE
通讯作者：
Jaffe AE
影响因子：
3.3
作者：
Ravizza, T;Vezzani, A
通讯作者：
Vezzani, A
DOI：
10.1016/s0006-291x(05)80225-6
发表时间：
1991-04-30
影响因子：
3.1
作者：
MINAMI, M;KURAISHI, Y;SATOH, M
通讯作者：
SATOH, M
影响因子：
3
作者：
Louboutin, Jean-Pierre;Strayer, David S.
通讯作者：
Strayer, David S.
影响因子：
5.6
作者：
Janigro, Damir
通讯作者：
Janigro, Damir