Selective changes in thalamic and cortical GABAA receptor subunits in a model of acquired absence epilepsy in the rat

Lipopolysaccharide induced increase in seizure activity in two animal models of absence epilepsy WAG/Rij and GAERS rats and Long Evans rats

“…There are also similarities with some differences between the 3 strains as far as the mechanisms of SWDs. It has been demonstrated, that (i) several neurotransmitter systems are involved in the pathophysiological processes leading to absence epileptic seizures and their maintenance/recurrence such as glutamatergic system, GABAergic system, dopaminergic and nucleosiderg system in GAERS rats, WAG/Rij rats and Long Evans rats (Bazyan and Van Luijtelaar, 2013;Depaulis and Van Luijtelaar, 2005;Kovács et al, 2013Kovács et al, , 2014Li et al, 2006;Polack and Charpier, 2006), (ii) the effects of anti-epileptic drugs on SWDs were similar in GAERS rats, WAG/Rij rats and Long Evans rats (e.g., ethosuximide, and valproate decreased the number of SWDs) (Chen et al, 2011;Depaulis and Van Luijtelaar, 2005;Shaw, 2004Shaw, , 2007, (iii) sodium channel (Nav1.1 and Nav1.6) expression was selectively increased in the somatosensory cortex of WAG/Rij rats in relation to age-dependent increase in seizure number and duration (Klein et al, 2004), (iv) selective decrease in thalamic (e.g., reticular thalamic nucleus) and cortical (e.g., somatosensory cortex) GABA (A) receptor subunits such as reduction of ␣3 subunit of GABA (A) receptor in reticular thalamic nucleus of WAG/Rij rats (Liu et al, 2007) may have a role in the pathophysiology of absence epilepsy in Long Evans rats, WAG/Rij rats and GAERS rats (Li et al, 2006;Spreafico et al, 1993), (v) mRNA levels for most GABA (B(1)) subunits were lower in WAG/Rij neocortex than in cortex of control nonepileptic rats, which can contribute to neocortical hyperexcitability and SWD generation (Merlo et al, 2007) whereas GABA (B(1)) subunit mRNA levels were higher and lower in the somatosensory cortex and ventrobasal thalamic nuclei of GAERS rats, respectively, compared with control animals (Princivalle et al, 2003), (vi) decreased alpha-amino-3-hydroxy-5-methyl-4-isoazolepropionic acid receptor (AMPA; AMPA-GluR4) and N-methyl-d-aspartate receptor (NMDA; NMDA-NR1) expression in the cortical focus of WAG/Rij animals (compared with non-epileptic control rats) and increased AMPA-GluR1/2 expression in GAERS rats in the somatosensory cortex may be in relation to hyperexcitability in somatosensory cortex and to SWD initiation (Van de BovenkampJanssen et al, 2006;Kennard et al, 2011), (vii) reduction of group-I metabotropic glutamate receptors (mGlu1 receptors) in ventrobasal thalamic nuclei and increased expression of group-II metabotropic glutamate receptors (mGlu2/3 receptors) in WAG/Rij rat somatosensory cortex and ventrobasal thalamic nuclei may be involved in the ge...…”

A γ2(R43Q) Mutation, Linked to Epilepsy in Humans, Alters GABAA Receptor Assembly and Modifies Subunit Composition on the Cell Surface

“…For instance, alteration or modulation of GABA neurotransmission plays an important role in epilepsy mechanisms and treatment (2)(3)(4). Furthermore, several mutations of GABA A receptor genes have recently been associated with epileptic syndromes (5)(6)(7)(8).…”

“…Furthermore, several mutations of GABA A receptor genes have recently been associated with epileptic syndromes (5)(6)(7)(8). These mutations offer an opportunity to obtain new insights into the structure and function of GABA A receptors (9,10) and may provide clues to implication of these receptors in epilepsies (4,11).…”

Decreased GABA receptor in the striatum and spatial recognition memory deficit in epileptic rats: Effect of Bacopa monnieri and bacoside-A

“…Differential expression of GABA A receptor subunit is a common phenomenon in epileptic condition (Porter et al, 2005;Paolo et al, 1999) and they represent a major aspect of homeostatic synaptic plasticity and contribute to the excitation/inhibition (E/I) balance under physiological conditions and upon pathological challenges (Fritschy, 2008). Alterations in GABA A receptor subunit expression and composition in epilepsy are well documented in human (Loup et al, 2000(Loup et al, , 2006 and in animal models (Gilby et al, 2005;Li et al, 2006;Nishimura et al, 2005;Peng et al, 2004;Roberts et al, 2005). The changes in GABA A receptor subunit contribute to the changes in inhibitory function that might underlie epileptogenesis and occurrence of chronic recurrent seizures (Jean-Marc, 2008).…”