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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
- Source :
- Journal of Neuroinflammation, Vol 17, Iss 1, Pp 1-15 (2020), Journal of Neuroinflammation
- Publication Year :
- 2020
- Publisher :
- BMC, 2020.
-
Abstract
- 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.
- Subjects :
- 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
Subjects
Details
- Language :
- English
- ISSN :
- 17422094
- Volume :
- 17
- Issue :
- 1
- Database :
- OpenAIRE
- Journal :
- Journal of Neuroinflammation
- Accession number :
- edsair.doi.dedup.....6a749cea093b9b3eda68c93cc429703b