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
Abstract Background A 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 dis...
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doaj-a24c5daa2e23441fb73fa685c2ac36bc2021-01-31T16:05:03ZengBMCJournal of Neuroinflammation1742-20942020-01-0117111510.1186/s12974-020-1718-7Decreased 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 modelJiong Yue0Jiaojiang He1Yujia Wei2Kaifeng Shen3Kefu Wu4Xiaolin Yang5Shiyong Liu6Chunqing Zhang7Hui Yang8Department of Neurosurgery, Xinqiao Hospital, Army Medical University (Third Military Medical University)Department of Neurosurgery, West China Hospital of Sichuan UniversityDepartment of Neurosurgery, Xinqiao Hospital, Army Medical University (Third Military Medical University)Department of Neurosurgery, Xinqiao Hospital, Army Medical University (Third Military Medical University)Department of Neurosurgery, Xinqiao Hospital, Army Medical University (Third Military Medical University)Department of Neurosurgery, Xinqiao Hospital, Army Medical University (Third Military Medical University)Department of Neurosurgery, Xinqiao Hospital, Army Medical University (Third Military Medical University)Department of Neurosurgery, Xinqiao Hospital, Army Medical University (Third Military Medical University)Department of Neurosurgery, Xinqiao Hospital, Army Medical University (Third Military Medical University)Abstract Background A 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. Methods The 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. Results The 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. Conclusions Taken 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.https://doi.org/10.1186/s12974-020-1718-7Temporal lobe epilepsyRev-ErbαNLRP3 inflammasomeNeuroinflammationNeuronal apoptosis |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Jiong Yue Jiaojiang He Yujia Wei Kaifeng Shen Kefu Wu Xiaolin Yang Shiyong Liu Chunqing Zhang Hui Yang |
spellingShingle |
Jiong Yue Jiaojiang He Yujia Wei Kaifeng Shen Kefu Wu Xiaolin Yang Shiyong Liu Chunqing Zhang Hui Yang 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 Journal of Neuroinflammation Temporal lobe epilepsy Rev-Erbα NLRP3 inflammasome Neuroinflammation Neuronal apoptosis |
author_facet |
Jiong Yue Jiaojiang He Yujia Wei Kaifeng Shen Kefu Wu Xiaolin Yang Shiyong Liu Chunqing Zhang Hui Yang |
author_sort |
Jiong Yue |
title |
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 |
title_short |
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 |
title_full |
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 |
title_fullStr |
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 |
title_full_unstemmed |
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 |
title_sort |
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 |
publisher |
BMC |
series |
Journal of Neuroinflammation |
issn |
1742-2094 |
publishDate |
2020-01-01 |
description |
Abstract Background A 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. Methods The 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. Results The 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. Conclusions Taken 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. |
topic |
Temporal lobe epilepsy Rev-Erbα NLRP3 inflammasome Neuroinflammation Neuronal apoptosis |
url |
https://doi.org/10.1186/s12974-020-1718-7 |
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