Activation of GABAA receptors controls mesiotemporal lobe epilepsy despite changes in chloride transporters expression: In vivo and in silico approach.

Activation of GABAA receptors controls mesiotemporal lobe epilepsy despite changes in chloride transporters expression: In vivo and in silico approach. Exp Neurol. 2016 Jul 19;284(Pt A):11-28 Authors: Stamboulian-Platel S, Legendre A, Chabrol T, Platel JC, Pernot F, Duveau V, Roucard C, Baudry M, Depaulis A Abstract Mesiotemporal lobe Epilepsy (MTLE), the most frequent form of focal epilepsy, is often drug-resistant. Enriching the epileptic focus with GABA-releasing engineered cells has been proposed as a strategy to prevent seizures. However, ex vivo data from animal models and MTLE patients suggest that, due to changes in chloride homeostasis, GABAA receptor activation is depolarizing and partly responsible for focal interictal discharges and seizure initiation. To understand how these two contradictory aspects of GABAergic neurotransmission coexist in MTLE, we used an established mouse model of MTLE presenting hippocampal sclerosis and recurrent hippocampal paroxysmal discharges (HPDs) 30-40days after a unilateral injection of kainate in the dorsal hippocampus. We first showed that injections of GABAA receptor agonists either systemically or directly into hippocampus suppressed HPDs. Western-blotting and immunostaining revealed that levels of α1, α3 and γ2 GABAA receptor subunits were increased in epileptic mice, compared to saline controls, while levels of R1 and R2 GABAB receptor subunits but also NR1, NR2A and NR2B NMDA rece...
Source: Experimental Neurology - Category: Neurology Authors: Tags: Exp Neurol Source Type: research