Curcumin reduces development of seizurelike events in the hippocampal-entorhinal cortex slice culture model for epileptogenesis
| Autor: | Jan A. Gorter, Eleonora Aronica, Erwin A. van Vliet, Pascal Chameau, Lieneke Kooijman, Wytse J. Wadman, Cato M. Drion |
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| Přispěvatelé: | Pathology, Amsterdam Neuroscience - Cellular & Molecular Mechanisms, AII - Inflammatory diseases, APH - Mental Health, APH - Aging & Later Life, Cellular and Computational Neuroscience (SILS, FNWI) |
| Jazyk: | angličtina |
| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
Curcumin mitogen-activated protein kinase antiepileptogenesis Hippocampus P70-S6 Kinase 1 Pharmacology Hippocampal formation Epileptogenesis Antioxidants Rats Sprague-Dawley 03 medical and health sciences chemistry.chemical_compound Organ Culture Techniques 0302 clinical medicine Seizures Animals Entorhinal Cortex rat PI3K/AKT/mTOR pathway mammalian target of rapamycin Chemistry TOR Serine-Threonine Kinases Entorhinal cortex Rats 030104 developmental biology Neurology inflammation seizurelike event Neurology (clinical) 030217 neurology & neurosurgery Transforming growth factor |
| Zdroj: | Epilepsia, 60(4), 605-614. Wiley-Blackwell |
| ISSN: | 0013-9580 |
| Popis: | OBJECTIVEInhibition of the mammalian target of rapamycin (mTOR) pathway could be antiepileptogenic in temporal lobe epilepsy (TLE), possibly via anti-inflammatory actions. We studied effects of the mTOR inhibitor rapamycin and the anti-inflammatory compound curcumin-also reported to inhibit the mTOR pathway-on epileptogenesis and inflammation in an in vitro organotypic hippocampal-entorhinal cortex slice culture model.METHODS Brain slices containing hippocampus and entorhinal cortex were obtained from 6-day-old rat pups and maintained in culture for up to 3 weeks. Rapamycin or curcumin was added to the culture medium from day 2 in vitro onward. Electrophysiological recordings revealed epileptiformlike activity that developed over 3 weeks.RESULTSIn week 3, spontaneous seizurelike events (SLEs) could be detected using whole cell recordings from CA1 principal neurons. The percentage of recorded CA1 neurons displaying SLEs was lower in curcumin-treated slice cultures compared to vehicle-treated slices (25.8% vs 72.5%), whereas rapamycin did not reduce SLE occurrence significantly (52%). Western blot for phosphorylated-S6 (pS6) and phosphorylated S6K confirmed that rapamycin inhibited the mTOR pathway, whereas curcumin only lowered pS6 expression at one phosphorylation site. Real-time quantitative polymerase chain reaction results indicated a trend toward lower expression of inflammatory markers IL-1β and IL-6 and transforming growth factor β after 3 weeks of treatment with rapamycin and curcumin compared to vehicle.SIGNIFICANCEOur results show that curcumin suppresses SLEs in the combined hippocampal-entorhinal cortex slice culture model and suggest that its antiepileptogenic effects should be further investigated in experimental models of TLE. |
| Databáze: | OpenAIRE |
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