PMID- 30747999
OWN - NLM
STAT- MEDLINE
DCOM- 20200413
LR  - 20211204
IS  - 1528-1167 (Electronic)
IS  - 0013-9580 (Linking)
VI  - 60
IP  - 4
DP  - 2019 Apr
TI  - Curcumin reduces development of seizurelike events in the hippocampal-entorhinal 
      cortex slice culture model for epileptogenesis.
PG  - 605-614
LID - 10.1111/epi.14667 [doi]
AB  - OBJECTIVE: Inhibition 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. RESULTS: In 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-1beta and IL-6 and transforming growth factor 
      beta after 3 weeks of treatment with rapamycin and curcumin compared to vehicle. 
      SIGNIFICANCE: Our 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.
CI  - Wiley Periodicals, Inc. (c) 2019 International League Against Epilepsy.
FAU - Drion, Cato M
AU  - Drion CM
AUID- ORCID: 0000-0002-3926-3110
AD  - Center for Neuroscience, Swammerdam Institute for Life Sciences, University of 
      Amsterdam, Amsterdam, The Netherlands.
FAU - Kooijman, Lieneke
AU  - Kooijman L
AD  - Center for Neuroscience, Swammerdam Institute for Life Sciences, University of 
      Amsterdam, Amsterdam, The Netherlands.
FAU - Aronica, Eleonora
AU  - Aronica E
AD  - Amsterdam UMC, University of Amsterdam, Department of (Neuro) Pathology, 
      Amsterdam Neuroscience, Amsterdam, The Netherlands.
AD  - Stichting Epilepsie Instellingen Nederland (SEIN), The Netherlands.
FAU - van Vliet, Erwin A
AU  - van Vliet EA
AUID- ORCID: 0000-0001-5747-3202
AD  - Center for Neuroscience, Swammerdam Institute for Life Sciences, University of 
      Amsterdam, Amsterdam, The Netherlands.
AD  - Amsterdam UMC, University of Amsterdam, Department of (Neuro) Pathology, 
      Amsterdam Neuroscience, Amsterdam, The Netherlands.
FAU - Wadman, Wytse J
AU  - Wadman WJ
AD  - Center for Neuroscience, Swammerdam Institute for Life Sciences, University of 
      Amsterdam, Amsterdam, The Netherlands.
FAU - Chameau, Pascal
AU  - Chameau P
AD  - Center for Neuroscience, Swammerdam Institute for Life Sciences, University of 
      Amsterdam, Amsterdam, The Netherlands.
FAU - Gorter, Jan A
AU  - Gorter JA
AD  - Center for Neuroscience, Swammerdam Institute for Life Sciences, University of 
      Amsterdam, Amsterdam, The Netherlands.
LA  - eng
GR  - EF 14-08/Epilepsie Fonds/International
GR  - 602102/European Union's Seventh Framework Program (FP7, Epitarget)/International
GR  - 602391/EPISTOP/International
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20190212
PL  - United States
TA  - Epilepsia
JT  - Epilepsia
JID - 2983306R
RN  - 0 (Antioxidants)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
RN  - IT942ZTH98 (Curcumin)
SB  - IM
MH  - Animals
MH  - Antioxidants/*pharmacology
MH  - Curcumin/*pharmacology
MH  - Entorhinal Cortex/*drug effects/metabolism
MH  - Hippocampus/*drug effects/metabolism
MH  - Organ Culture Techniques
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Seizures/*metabolism
MH  - TOR Serine-Threonine Kinases/antagonists & inhibitors
OTO - NOTNLM
OT  - antiepileptogenesis
OT  - inflammation
OT  - mammalian target of rapamycin
OT  - mitogen-activated protein kinase
OT  - rat
OT  - seizurelike event
EDAT- 2019/02/13 06:00
MHDA- 2020/04/14 06:00
CRDT- 2019/02/13 06:00
PHST- 2018/10/31 00:00 [received]
PHST- 2019/01/17 00:00 [revised]
PHST- 2019/01/17 00:00 [accepted]
PHST- 2019/02/13 06:00 [pubmed]
PHST- 2020/04/14 06:00 [medline]
PHST- 2019/02/13 06:00 [entrez]
AID - 10.1111/epi.14667 [doi]
PST - ppublish
SO  - Epilepsia. 2019 Apr;60(4):605-614. doi: 10.1111/epi.14667. Epub 2019 Feb 12.