GABAergic neurons and GABAA-receptors in temporal lobe epilepsy

Fritschy, Jean‐Marc; Kiener, Tania; Bouilleret, Viviane; Loup, Fabienne

doi:10.1016/s0197-0186(99)00040-6

Cited by 149 publications

(119 citation statements)

References 47 publications

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“…Inhibitory mechanisms are altered in patients presenting with TLE and in animal models mimicking this disorder (Obenaus et al, 1993;Bernard et al, 2000;Houser and Escaplez, 1996;Fritschy et al, 1999;Gorter et al, 2001;Knopp et al, 2008;Maglóczky and Freund, 2005;van Vliet et al, 2004). However, these changes are complex and they cannot be epitomized as a simple, general decrease in the number of GABAergic cells along with inhibition collapse.…”

Section: Gaba a Receptor-mediated Inhibition In Temporal Lobe Epilepsymentioning

confidence: 99%

GABAergic synchronization in the limbic system and its role in the generation of epileptiform activity

Avoli¹,

Curtis²

2011

Progress in Neurobiology

227

253

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GABA is the main inhibitory neurotransmitter in the adult forebrain, where it activates ionotropic type A and metabotropic type B receptors. Early studies have shown that GABA A receptormediated inhibition controls neuronal excitability and thus the occurrence of seizures. However, more complex, and at times unexpected, mechanisms of GABAergic signaling have been identified during epileptiform discharges over the last few years. Here, we will review experimental data that point at the paradoxical role played by GABA A receptor-mediated mechanisms in synchronizing neuronal networks, and in particular those of limbic structures such as the hippocampus, the entorhinal and perirhinal cortices, or the amygdala. After having summarized the fundamental characteristics of GABA A receptor-mediated mechanisms, we will analyze their role in the generation of network oscillations and their contribution to epileptiform synchronization. Whether and how GABA A receptors influence the interaction between limbic networks leading to ictogenesis will be also reviewed. Finally, we will consider the role of altered inhibition in the human epileptic brain along with the ability of GABA A receptor-mediated conductances to generate synchronous depolarizing events that may lead to ictogenesis in human epileptic disorders as well.

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Section: Gaba a Receptor-mediated Inhibition In Temporal Lobe Epilepsymentioning

confidence: 99%

GABAergic synchronization in the limbic system and its role in the generation of epileptiform activity

Avoli¹,

Curtis²

2011

Progress in Neurobiology

227

253

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“…Several studies report the loss of hippocampal inhibitory interneurons in rodent models of epilepsy (Cavazos et al, 1994; Fritschy et al, 1999; Bouilleret et al, 2000; Gorter et al, 2001), as well as in human epileptic patients (Andrioli et al, 2007). These observations are further corroborated by genetic studies using interneuron‐deficient transgenic mice suggesting that particular gene defects affect specific interneuronal development, resulting in seizures (Jones‐Davies et al ., 2009).…”

Section: Introductionmentioning

confidence: 99%

Cannabidiol exerts antiepileptic effects by restoring hippocampal interneuron functions in a temporal lobe epilepsy model

Khan

Shekh‐Ahmad²,

Khalil³

et al. 2018

British J Pharmacology

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Background and PurposeA non‐psychoactive phytocannabinoid, cannabidiol (CBD), shows promising results as an effective potential antiepileptic drug in some forms of refractory epilepsy. To elucidate the mechanisms by which CBD exerts its anti‐seizure effects, we investigated its effects at synaptic connections and on the intrinsic membrane properties of hippocampal CA1 pyramidal cells and two major inhibitory interneurons: fast spiking, parvalbumin (PV)‐expressing and adapting, cholecystokinin (CCK)‐expressing interneurons. We also investigated whether in vivo treatment with CBD altered the fate of CCK and PV interneurons using immunohistochemistry.Experimental ApproachElectrophysiological intracellular whole‐cell recordings combined with neuroanatomy were performed in acute brain slices of rat temporal lobe epilepsy in in vivo (induced by kainic acid) and in vitro (induced by Mg2+‐free solution) epileptic seizure models. For immunohistochemistry experiments, CBD was administered in vivo (100 mg·kg−1) at zero time and 90 min post status epilepticus, induced with kainic acid.Key ResultsBath application of CBD (10 μM) dampened excitability at unitary synapses between pyramidal cells but enhanced inhibitory synaptic potentials elicited by fast spiking and adapting interneurons at postsynaptic pyramidal cells. Furthermore, CBD restored impaired membrane excitability of PV, CCK and pyramidal cells in a cell type‐specific manner. These neuroprotective effects of CBD were corroborated by immunohistochemistry experiments that revealed a significant reduction in atrophy and death of PV‐ and CCK‐expressing interneurons after CBD treatment.Conclusions and ImplicationsOur data suggest that CBD restores excitability and morphological impairments in epileptic models to pre‐epilepsy control levels through multiple mechanisms to reinstate normal network function.

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“…dos animais durante 1h e também com 24h de observação, revelando um porcentual de ocorrência de morte semelhante nos animais jovens independentemente do tempo de observação. O mesmo fato parece não ocorrer nos ratos adultos, Alguns estudos têm sugerido, na fase aguda das convulsões, relação quase imediata da acetilcolina com outros sistemas de neurotransmissão (adrenérgico, dopaminér-gico e serotonérgico), uma vez que têm sido observados efeitos rápidos nas concentrações de noradrenalina, dopamina e serotonina 7,14 . Nos ratos jovens, em particular, a influência da imaturidade na relação entre os sistemas pode promover ações semelhantes do sistema colinérgico na fase aguda das convulsões independentemente do tempo, limitando a participação de mecanismos atenuantes da ativação colinérgica, provavelmente existentes no cé-rebro maduro.…”

Section: Discussionunclassified

“…Vários estudos 4,6 , porém, indicam aumento não somente na atividade colinérgica pós-sináptica, mas na pré-sináptica também. Contudo, co- Para esse fim, vários aspectos têm sido observados, a saber: a interferência do sistema de neurotransmissão muscarínico 6 , dopaminérgico 9,10 , glutamatérgico 11,12 , e GABAérgico [13][14][15] , e o estudo dos segundos mensageiros 6 nas convulsões utilizando pilocarpina 400mg/Kg 13 . Tem sido feita outra abordagem que favorece o conhecimento da epilepsia em relação à idade: o estudo das convulsões em animais na fase de desenvolvimento 16 , uma vez que o cérebro imaturo, com suas inervações e densidade de receptores ainda em desenvolvimento, pode ajudar na investigação da origem das convulsões, incluindo a relação entre a ativação do receptor e o processo de transdução de sinal 16 e as possíveis alterações nas concentrações dos neurotransmissores 15 .…”

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Alterações agudas dos níveis de neurotransmissores em corpo estriado de ratos jovens após estado epiléptico induzido por pilocarpina

Freitas

Sousa

Vasconcelos

et al. 2003

Arq. Neuro-Psiquiatr.

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RESUMO -Altas doses de agonista colinérgico muscarínico, pilocarpina, produzem alterações comportamentais, convulsões e estado epiléptico em ratos. O objetivo desse estudo foi verificar as alterações nas concentrações dos neurotransmissores em corpo estriado de ratos em desenvolvimento após estado epiléptico induzido pela pilocarpina. Ratas Wistar foram tratadas com uma única dose de pilocarpina (400mg/Kg; s.c.). Controles receberam salina. A concentração dos neurotransmissores foi determinada através do HPLC, no corpo estriado de ratos que no período de observação de 1 e 24h desencadearam estado epiléptico e não sobreviveram à fase aguda do quadro convulsivo. Foi observada redução nos níveis de dopamina, serotonina, ácido dihidroxifenilacético, ácido 5-hidroxiindolacético, e aumento no ácido 4-hidroxi-3-metoxi-fenilacético. Os resultados mostraram que a ativação do sistema colinérgico pode interagir com os sistemas dopaminérgico e serotonérgico nos mecanismos referentes à fase aguda do processo convulsivo.PALAVRAS-CHAVE: dopamina, serotonina, convulsão, pilocarpina, corpo estriado.Acute alterations of neurotransmitters levels in striatum of young rat after pilocarpine-induced status Acute alterations of neurotransmitters levels in striatum of young rat after pilocarpine-induced status Acute alterations of neurotransmitters levels in striatum of young rat after pilocarpine-induced status Acute alterations of neurotransmitters levels in striatum of young rat after pilocarpine-induced status Acute alterations of neurotransmitters levels in striatum of young rat after pilocarpine-induced status epilepticus epilepticus epilepticus epilepticus epilepticus ABSTRACT -High doses of the muscarinic cholinergic agonist, pilocarpine, result in behavioural changes, seizures and status epilepticus in rats. The purpose of the present work is to invetigate the striatal neurotransmissors level in young rats after status epilepticus induced by pilocarpine. Wistar rats were treated with a single dose of pilocarpine (400mg/Kg; s.c.). Controls received saline. Young animals were closed observed for behavioural changes during 1 and 24h. In these periods, the animals that developed status epilepticus and didn't survive this acute phase of seizures had the brains removed and striatal neurotransmissors level determined by HPLC. The concentration of dopamine, serotonine, dihydroxyphenylacetic acid, 5-hydroxyindolacetic acid was reduced and an increase in 4-hydroxy-3-methoxy-phenylacetic acid was observed. These results suggest that cholinergic activation can interage with dopaminergic and serotonergic systems in acute phase of the convulsive process in immature striatum.KEY WORDS: dopamine, serotonine, seizures, pilocarpine, striatum.Agonistas muscarínicos administrados em altas doses induzem a produção de convulsões motoras límbicas e estado epiléptico em ratos adultos 1,2 . O modelo de convulsão com dose alta de pilocarpina (400mg/Kg) revela o processo convulsivo através de alterações comportamentais, eletroencefalográficas e pela pres...

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GABAergic neurons and GABAA-receptors in temporal lobe epilepsy

Cited by 149 publications

References 47 publications

GABAergic synchronization in the limbic system and its role in the generation of epileptiform activity

GABAergic synchronization in the limbic system and its role in the generation of epileptiform activity

Cannabidiol exerts antiepileptic effects by restoring hippocampal interneuron functions in a temporal lobe epilepsy model

Alterações agudas dos níveis de neurotransmissores em corpo estriado de ratos jovens após estado epiléptico induzido por pilocarpina

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