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NLRP3 inflammasome and endoplasmic reticulum stress in the epileptogenic zone in temporal lobe epilepsy: molecular insights into their interdependence
- Source :
- Neuropathology and Applied Neurobiology. 46:770-785
- Publication Year :
- 2020
- Publisher :
- Wiley, 2020.
-
Abstract
- Aim Nod-like receptor protein 3 (NLRP3) inflammasome-mediated inflammation has emerged as a contributor to epileptogenesis. Endoplasmic reticulum stress (ERS) plays an important role in epilepsy-induced neurodegeneration. NLRP3 activation and ERS reactions share the same induction factors, suggesting that these processes may be interdependent. However, the correlation between NLRP3 and ERS in TLE has not been confirmed. Methods The expression patterns of NLRP3 inflammasome and ERS-related markers in the temporal neocortices of TLE patients were investigated by western blotting, immunohistochemistry and immunofluorescent labelling. Correlations between the protein levels of NLRP3 and the expression of ERS-related markers were assessed using Spearman's rank correlation test. To observe the relationship between the NLRP3 inflammasome and ERS, inhibitors were used in a status epilepticus (SE) model. Results Our results show that NLRP3 inflammasome components and ERS-related markers were upregulated in the temporal neocortices of TLE patients, and were mainly localized to neurons, astrocytes and microglia. We found a positive correlation between the protein levels of NLRP3 and the expression of ERS-related markers in the temporal neocortices of 20 TLE patients. Furthermore, after blocking the NLRP3 inflammasome with MCC950, the expression of ERS-related markers was markedly decreased in the hippocampi of SE mice. Moreover, TUDCA, a specific ERS inhibitor, also reduced the expression of NLRP3 components in the hippocampus under SE conditions. Conclusion Taken together, our data reveal the interdependence of the NLRP3 inflammasome and ERS in the epileptogenic zone of TLE patients and in the hippocampi of mice in the early post-SE phase.
- Subjects :
- Adult
Male
0301 basic medicine
Histology
Adolescent
Status epilepticus
Biology
Hippocampus
Epileptogenesis
Pathology and Forensic Medicine
Mice
Young Adult
03 medical and health sciences
Status Epilepticus
0302 clinical medicine
Downregulation and upregulation
Physiology (medical)
NLR Family, Pyrin Domain-Containing 3 Protein
medicine
Animals
Humans
Neuroinflammation
Inflammation
Neurons
integumentary system
Microglia
Endoplasmic reticulum
Neurodegeneration
Inflammasome
Endoplasmic Reticulum Stress
medicine.disease
Cell biology
Disease Models, Animal
030104 developmental biology
medicine.anatomical_structure
Epilepsy, Temporal Lobe
nervous system
Neurology
Astrocytes
Female
Neurology (clinical)
medicine.symptom
030217 neurology & neurosurgery
medicine.drug
Subjects
Details
- ISSN :
- 13652990 and 03051846
- Volume :
- 46
- Database :
- OpenAIRE
- Journal :
- Neuropathology and Applied Neurobiology
- Accession number :
- edsair.doi.dedup.....4d7cf1337befe597162008201fd4012e