Decreased expression of Rev-Erbα in the epileptic foci of temporal lobe epilepsy and activation of Rev-Erbα have anti-inflammatory and neuroprotective effects in the pilocarpine model
| Autor: | Kefu Wu, Xiaolin Yang, Kaifeng Shen, Yu-Jia Wei, Shi-Yong Liu, Jiong Yue, Jiaojiang He, Hui Yang, Chun-Qing Zhang |
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| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
Male
Pathology Pyrrolidines Anti-Inflammatory Agents Hippocampus Convulsants lcsh:RC346-429 Mice Status Epilepticus Neuroinflammation Gliosis Temporal lobe epilepsy Neocortex TUNEL assay Microglia Neuronal apoptosis General Neuroscience Pilocarpine Temporal Lobe medicine.anatomical_structure Neuroprotective Agents Rev-Erbα Neurology Cytokines Encephalitis medicine.symptom medicine.drug Adult medicine.medical_specialty Adolescent Immunology Status epilepticus Thiophenes Biology Neuroprotection Cellular and Molecular Neuroscience Young Adult medicine Animals Humans lcsh:Neurology. Diseases of the nervous system Research NLRP3 inflammasome Mice Inbred C57BL Epilepsy Temporal Lobe Gene Expression Regulation nervous system Nuclear Receptor Subfamily 1 Group D Member 1 |
| Zdroj: | Journal of Neuroinflammation, Vol 17, Iss 1, Pp 1-15 (2020) Journal of Neuroinflammation |
| ISSN: | 1742-2094 |
| Popis: | BackgroundA hallmark of temporal lobe epilepsy (TLE) is brain inflammation accompanied by neuronal demise. Accumulating evidence demonstrates that Rev-Erbα is involved in regulating neuroinflammation and determining the fate of neurons. Therefore, we studied the expression and cellular distribution of Rev-Erbα in the epileptogenic zone of TLE and the effect of treatment with the Rev-Erbα specific agonist SR9009 in the pilocarpine model.MethodsThe expression pattern of Rev-Erbα was investigated by western blotting, immunohistochemistry, and immunofluorescence labeling in patients with TLE. Next, the effects of SR9009 on neuroinflammation, neuronal apoptosis, and neuronal loss in the mouse hippocampus 7 days after status epilepticus (SE) were assessed by western blotting, immunofluorescence labeling staining, and TUNEL staining.ResultsThe western blotting, immunohistochemistry, and immunofluorescence labeling results revealed that Rev-Erbα was downregulated in the epileptogenic zone of TLE patients and mainly localized in neurons, astrocytes, and presumably microglia. Meanwhile, the expression of Rev-Erbα was decreased in the hippocampus and temporal neocortex of mice treated with pilocarpine in the early post-SE and chronic phases. Interestingly, the expression of Rev-Erbα in the normal hippocampus showed a 24-h rhythm; however, the rhythmicity was disturbed in the early phase after SE, and this disturbance was still present in epileptic animals. Our further findings revealed that treatment with SR9009 inhibited NLRP3 inflammasome activation, inflammatory cytokine (IL-1β, IL-18, IL-6, and TNF-α) production, astrocytosis, microgliosis, and neuronal damage in the hippocampus after SE.ConclusionsTaken together, these results suggested that a decrease in Rev-Erbα in the epileptogenic zone may contribute to the process of TLE and that the activation of Rev-Erbα may have anti-inflammatory and neuroprotective effects. |
| Databáze: | OpenAIRE |
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