Effect of spontaneous seizures on GABAA receptor α4 subunit expression in an animal model of temporal lobe epilepsy

ObjectiveTemporal lobe epilepsy (TLE) is frequently medically intractable and often progressive. Compromised inhibitory neurotransmission due to altered -aminobutyric acid (GABA)(A) receptor 4 subunit (GABA(A)R4) expression has been emphasized as a potential contributor to the initial development of epilepsy following a brain insult (primary epileptogenesis), but the regulation of GABA(A)R4 during chronic epilepsy, specifically, how expression is altered following spontaneous seizures, is less well understood. MethodsContinuous video-electroencephalography (EEG) recordings from rats with pilocarpine-induced TLE were used to capture epileptic animals within 3h of a spontaneous seizure (SS), or >24h after the last SS, to determine whether recent occurrence of a seizure was associated with altered levels of GABA(A)R4 expression. We further evaluated whether this GABA(A)R4 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). ResultsElevated levels of GABA(A)R4 messenger RNA (mRNA) and protein were observed following spontaneous seizures, and were associated with higher levels of BDNF and Egr3 mRNA. SignificanceThese data suggest that spontaneous, recurrent seizures that define chronic epilepsy may influence changes in GABA(A)R4 expression, and that signaling pathways known to regulate GABA(A)R4 expression after status epilepticus may also be activated after spontaneous seizures in chronically epileptic animals.