PMID- 25223733 OWN - NLM STAT- MEDLINE DCOM- 20150128 LR - 20211021 IS - 1528-1167 (Electronic) IS - 0013-9580 (Print) IS - 0013-9580 (Linking) VI - 55 IP - 11 DP - 2014 Nov TI - Effect of spontaneous seizures on GABAA receptor alpha4 subunit expression in an animal model of temporal lobe epilepsy. PG - 1826-33 LID - 10.1111/epi.12771 [doi] AB - OBJECTIVE: Temporal lobe epilepsy (TLE) is frequently medically intractable and often progressive. Compromised inhibitory neurotransmission due to altered gamma-aminobutyric acid (GABA)A receptor alpha4 subunit (GABAA Ralpha4) expression has been emphasized as a potential contributor to the initial development of epilepsy following a brain insult (primary epileptogenesis), but the regulation of GABAA Ralpha4 during chronic epilepsy, specifically, how expression is altered following spontaneous seizures, is less well understood. METHODS: Continuous video-electroencephalography (EEG) recordings from rats with pilocarpine-induced TLE were used to capture epileptic animals within 3 h of a spontaneous seizure (SS), or >24 h after the last SS, to determine whether recent occurrence of a seizure was associated with altered levels of GABAA Ralpha4 expression. We further evaluated whether this GABAA Ralpha4 plasticity is regulated by signaling mechanisms active in primary epileptogenesis, specifically, increases in brain-derived neurotrophic factor (BDNF) and early growth response factor 3 (Egr3). RESULTS: Elevated levels of GABAA Ralpha4 messenger RNA (mRNA) and protein were observed following spontaneous seizures, and were associated with higher levels of BDNF and Egr3 mRNA. SIGNIFICANCE: These data suggest that spontaneous, recurrent seizures that define chronic epilepsy may influence changes in GABAA Ralpha4 expression, and that signaling pathways known to regulate GABAA Ralpha4 expression after status epilepticus may also be activated after spontaneous seizures in chronically epileptic animals. CI - Wiley Periodicals, Inc. (c) 2014 International League Against Epilepsy. FAU - Grabenstatter, Heidi L AU - Grabenstatter HL AD - Department of Pediatrics, Section of Neurology, Translational Epilepsy Research Program, University of Colorado, AMC, Aurora, Colorado, U.S.A. FAU - Cogswell, Meaghan AU - Cogswell M FAU - Cruz Del Angel, Yasmin AU - Cruz Del Angel Y FAU - Carlsen, Jessica AU - Carlsen J FAU - Gonzalez, Marco I AU - Gonzalez MI FAU - Raol, Yogendra H AU - Raol YH FAU - Russek, Shelley J AU - Russek SJ FAU - Brooks-Kayal, Amy R AU - Brooks-Kayal AR LA - eng GR - R01 NS051710/NS/NINDS NIH HHS/United States GR - R21 NS083057/NS/NINDS NIH HHS/United States GR - R01NS051710/NS/NINDS NIH HHS/United States GR - P30 NS048154/NS/NINDS NIH HHS/United States GR - T32 GM008541/GM/NIGMS NIH HHS/United States GR - UL1 TR001082/TR/NCATS NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural PT - Research Support, Non-U.S. Gov't DEP - 20140915 PL - United States TA - Epilepsia JT - Epilepsia JID - 2983306R RN - 0 (Gabra4 protein, rat) RN - 0 (Receptors, GABA-A) RN - 01MI4Q9DI3 (Pilocarpine) RN - 56-12-2 (gamma-Aminobutyric Acid) SB - IM MH - Animals MH - Disease Models, Animal MH - Epilepsy, Temporal Lobe/chemically induced/*metabolism MH - Pilocarpine/pharmacology MH - Rats, Sprague-Dawley MH - Receptors, GABA-A/*metabolism MH - Seizures/chemically induced/*metabolism MH - gamma-Aminobutyric Acid/*metabolism PMC - PMC4596257 MID - NIHMS619972 OTO - NOTNLM OT - GABAA receptor OT - Pilocarpine OT - Spontaneous seizure COIS- Disclosure of Conflicts of Interests: None of the authors has any conflict of interest to disclose. We confirm that we have read the Journal's position on issues involved in ethical publication and affirm that this report is consistent with those guidelines. EDAT- 2014/09/17 06:00 MHDA- 2015/01/30 06:00 PMCR- 2015/11/01 CRDT- 2014/09/17 06:00 PHST- 2014/07/31 00:00 [accepted] PHST- 2014/09/17 06:00 [entrez] PHST- 2014/09/17 06:00 [pubmed] PHST- 2015/01/30 06:00 [medline] PHST- 2015/11/01 00:00 [pmc-release] AID - 10.1111/epi.12771 [doi] PST - ppublish SO - Epilepsia. 2014 Nov;55(11):1826-33. doi: 10.1111/epi.12771. Epub 2014 Sep 15.