title: Effect of spontaneous seizures on GABAA receptor α4 subunit expression in an animal model of temporal lobe epilepsy.
abstract: OBJECTIVE
  Temporal lobe epilepsy (TLE) is frequently medically intractable and often progressive. Compromised inhibitory neurotransmission due to altered γ-aminobutyric acid (GABA)A receptor α4 subunit (GABAA Rα4) 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 Rα4 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 Rα4 expression. We further evaluated whether this GABAA Rα4 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 Rα4 messenger RNA (mRNA) and protein were observed following spontaneous seizures, and were associated with higher levels of BDNF and Egr3 mRNA.
  
  
  CONCLUSIONS
  These data suggest that spontaneous, recurrent seizures that define chronic epilepsy may influence changes in GABAA Rα4 expression, and that signaling pathways known to regulate GABAA Rα4 expression after status epilepticus may also be activated after spontaneous seizures in chronically epileptic animals.
authors.affiliation: Department of Pediatrics, Section of Neurology, Translational Epilepsy Research Program, University of Colorado, AMC, Aurora, Colorado, U.S.A.
authors.forename: Heidi L
authors.initials: HL
authors.lastname: Grabenstatter
authors.forename: Meaghan
authors.initials: M
authors.lastname: Cogswell
authors.forename: Yasmin
authors.initials: Y
authors.lastname: Cruz Del Angel
authors.forename: Jessica
authors.initials: J
authors.lastname: Carlsen
authors.forename: Marco I
authors.initials: MI
authors.lastname: Gonzalez
authors.forename: Yogendra H
authors.initials: YH
authors.lastname: Raol
authors.forename: Shelley J
authors.initials: SJ
authors.lastname: Russek
authors.forename: Amy R
authors.initials: AR
authors.lastname: Brooks-Kayal
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D004833:Epilepsy, Temporal Lobe / Q000139:chemically induced / Q000378:metabolism*; D010862:Pilocarpine / Q000494:pharmacology; D017207:Rats, Sprague-Dawley; D011963:Receptors, GABA-A / Q000378:metabolism*; D012640:Seizures / Q000139:chemically induced / Q000378:metabolism*; D005680:gamma-Aminobutyric Acid / Q000378:metabolism*
chemical_list: C546262:Gabra4 protein, rat; D011963:Receptors, GABA-A; D010862:Pilocarpine; D005680:gamma-Aminobutyric Acid
keywords: GABAA receptor; Pilocarpine; Spontaneous seizure