TGF-β Activated Kinase 1 (TAK1) Is Activated in Microglia After Experimental Epilepsy and Contributes to Epileptogenesis

被引：0
作者：
Dilaware Khan
Peter Bedner
Julia Müller
Fabienne Lülsberg
Lukas Henning
Marco Prinz
Christian Steinhäuser
Sajjad Muhammad
机构：
[1] Heinrich-Heine-University,Department of Neurosurgery, Medical Faculty and University Hospital Düsseldorf
[2] University of Bonn,Institute of Cellular Neurosciences, Medical Faculty
[3] University of Freiburg,Institute of Neuropathology, Faculty of Medicine
[4] University of Freiburg,Center for Basics in NeuroModulation (NeuroModulBasics), Faculty of Medicine
[5] University of Freiburg,Signalling Research Centres BIOSS and CIBSS
[6] University of Helsinki and Helsinki University Hospital,Department of Neurosurgery
来源：
Molecular Neurobiology | 2023年 / 60卷
关键词：
Inflammation; Epilepsy; TAK1; Microglia;
D O I：
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学科分类号：
摘要：
Increasing evidence suggests that inflammation promotes epileptogenesis. TAK1 is a central enzyme in the upstream pathway of NF-κB and is known to play a central role in promoting neuroinflammation in neurodegenerative diseases. Here, we investigated the cellular role of TAK1 in experimental epilepsy. C57Bl6 and transgenic mice with inducible and microglia-specific deletion of Tak1 (Cx3cr1CreER:Tak1fl/fl) were subjected to the unilateral intracortical kainate mouse model of temporal lobe epilepsy (TLE). Immunohistochemical staining was performed to quantify different cell populations. The epileptic activity was monitored by continuous telemetric electroencephalogram (EEG) recordings over a period of 4 weeks. The results show that TAK1 was activated predominantly in microglia at an early stage of kainate-induced epileptogenesis. Tak1 deletion in microglia resulted in reduced hippocampal reactive microgliosis and a significant decrease in chronic epileptic activity. Overall, our data suggest that TAK1-dependent microglial activation contributes to the pathogenesis of chronic epilepsy.
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页码：3413 / 3422
页数：9
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