Targeting CCL5 signaling attenuates neuroinflammation after seizure
Background Epilepsy is a neurological condition that causes unprovoked, recurrent seizures. Accumulating evidence from clinical and experimental studies indicates that neuroinflammation exacerbates seizure activity. Methods We investigated the transcriptional changes occurring in specific brain doma...
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Published in | CNS neuroscience & therapeutics Vol. 29; no. 1; pp. 317 - 330 |
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Main Authors | , , , , , |
Format | Journal Article |
Language | English |
Published |
England
John Wiley & Sons, Inc
01.01.2023
John Wiley and Sons Inc |
Subjects | |
Online Access | Get full text |
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Summary: | Background
Epilepsy is a neurological condition that causes unprovoked, recurrent seizures. Accumulating evidence from clinical and experimental studies indicates that neuroinflammation exacerbates seizure activity.
Methods
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.
Results
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.
Conclusions
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 KA‐induced 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. |
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Bibliography: | Zhuoran Zhang and Yan Li, contributed equally to this work. ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 |
ISSN: | 1755-5930 1755-5949 |
DOI: | 10.1111/cns.14006 |