Under stressful conditions activation of the ionotropic P2X7 receptor differentially regulates GABA and glutamate release from nerve terminals of the rat cerebral cortex

Barros‐Barbosa, Aurora; Oliveira, Â.; Lobo, M. Graça; Cordeiro, Miguel; Correia-de-Sá, Paulo

doi:10.1016/j.neuint.2017.11.005

Cited by 19 publications

(20 citation statements)

References 52 publications

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“…The P2X7R increases glutamate secretion in a vesicular and non-vesicular manner (Sperlagh et al, 2002;Cho et al, 2010). It also affects GABA and glutamate reuptake in a calciumdependent manner (Barros-Barbosa et al, 2018). The P2X7R was found to be non-desensitizing, and it allows substantial calcium influx (Fischer et al, 2016).…”

Section: Introductionmentioning

confidence: 99%

The Role of NMDA Receptors in the Effect of Purinergic P2X7 Receptor on Spontaneous Seizure Activity in WAG/Rij Rats With Genetic Absence Epilepsy

et al. 2020

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P2X7 receptors (P2X7Rs) are ATP sensitive cation channels and have been shown to be effective in various epilepsy models. Absence epilepsy is a type of idiopathic, generalized, non-convulsive epilepsy. Limited data exist on the role of P2X7Rs and no data has been reported regarding the interaction between P2X7Rs and glutamate receptor NMDA in absence epilepsy. Thus, this study was designed to investigate the role of P2X7 and NMDA receptors and their possible interaction in WAG/Rij rats with absence epilepsy. Permanent cannula and electrodes were placed on the skulls of the animals. After the healing period of the electrode and cannula implantation, ECoG recordings were obtained during 180 min before and after drug injections. P2X7R agonist BzATP, at doses of 50 µg and 100 µg (intracerebroventricular; i.c.v.) and antagonist A-438079, at doses of 20 µg and 40 µg (i.c.v.) were administered alone or prior to memantine (5 mg/kg, intraperitoneal; i.p.) injection. The total number (in every 20 min), the mean duration, and the amplitude of spike-wave discharges (SWDs) were calculated and compared. Rats were decapitated and the right and left hemisphere, cerebellum, and brainstem were separated for the measurements of the advanced oxidation protein product (AOPP), malondialdehyde (MDA), superoxide dismutase (SOD), glutathione (GSH), catalase (CAT), glutathione peroxide (GPx), and glutathione reductase (GR). BzATP and A-438079 did not alter measured SWDs parameters, whereas memantine reduced them, which is considered anticonvulsant. BzATP did not alter the anticonvulsant effect of memantine, while A-438079 decreased the effect of memantine. Administration of BzATP increased the levels of SOD and GR in cerebrum hemispheres. A-438079 did not alter any of the biochemical parameters. Memantine reduced the levels of MDA, GSH, and GR while increased the level of CAT in the cerebrum. Administration of BzATP before memantine abolished the effect of memantine on MDA levels. The evidence from this study suggests that P2X7Rs

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Section: Introductionmentioning

confidence: 99%

The Role of NMDA Receptors in the Effect of Purinergic P2X7 Receptor on Spontaneous Seizure Activity in WAG/Rij Rats With Genetic Absence Epilepsy

et al. 2020

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“…Substitution of Na + with NMDG (128 mM) in the incubation medium transiently increased [ 3 H]GABA and [ 14 C]Glu outflow by rat cortical synaptosomes (see e.g., Wu et al, 2006 ). Previously, we showed that disruption of the transmembrane Na + gradient leading to a reversal of amino-acid transporters to operate in the releasing mode can affect differentially the outflow of [ 3 H]GABA and [ 14 C]Glu ( Barros-Barbosa et al, 2018 ).…”

Section: Resultsmentioning

confidence: 99%

“…Previously, our group demonstrated that MP (300 μM) favors the release of ATP from resting motor nerve terminals ( Oliveira et al, 2015 ) and the nucleotide acting via ionotropic P2X7 receptors can differentially affect GABA and Glu release (and uptake) from isolated nerve terminals of the rat cerebral cortex ( Barros-Barbosa et al, 2015 , 2018 ). Confocal micrographs depicted in Figure 5 show that the fairly specific antibody against the C-terminal of the rat P2X7 receptor (#APR-004) co-localizes extensively with the synaptic nerve terminal marker, VAMP-1, but no color merge was detected in GFAP-positive astrocytic cells of the rat hippocampus.…”

Section: Resultsmentioning

confidence: 99%

“…Re-sealed nerve terminal membranes isolated from the rat hippocampus using this methodology allows processing larger amounts of tissue compared to synaptosomal preparations, while taking up and release [ 3 H]GABA and [ 14 C]glutamate via Na + -dependent high-affinity transporters with a similar kinetics. This method is relevant in order to take full advantage of scarce human brain tissue (from cadaveric samples and surgical resections of epileptic foci) often tested in parallel by our group (see Barros-Barbosa et al, 2015 , 2016 , 2018 ).…”

Section: Methodsmentioning

confidence: 99%

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Non-genomic Actions of Methylprednisolone Differentially Influence GABA and Glutamate Release From Isolated Nerve Terminals of the Rat Hippocampus

Neiva

Caulino-Rocha

Ferreirinha

et al. 2020

Front. Mol. Neurosci.

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Corticosteroids exert a dual role in eukaryotic cells through their action via (1) intracellular receptors (slow genomic responses), or (2) membrane-bound receptors (fast non-genomic responses). Highly vulnerable regions of the brain, like the hippocampus, express high amounts of corticosteroid receptors, yet their actions on ionic currents and neurotransmitters release are still undefined. Here, we investigated the effect of methylprednisolone (MP) on GABA and glutamate (Glu) release from isolated nerve terminals of the rat hippocampus. MP favored both spontaneous and depolarization-evoked [ 14 C]Glu release from rat hippocampal nerve terminals, without affecting [ 3 H]GABA outflow. Facilitation of [ 14 C]Glu release by MP is mediated by a Na + -dependent Ca 2+ -independent non-genomic mechanism relying on the activation of membrane-bound glucocorticoid (GR) and mineralocorticoid (MR) receptors sensitive to their antagonists mifepristone and spironolactone, respectively. The involvement of Na + -dependent high-affinity EAAT transport reversal was inferred by blockage of MP-induced [ 14 C]Glu release by DL-TBOA. Depolarization-evoked [ 3 H]GABA release in the presence of MP was partially attenuated by the selective P2X7 receptor antagonist A-438079, but this compound did not affect the release of [ 14 C]Glu. Data indicate that MP differentially affects GABA and glutamate release from rat hippocampal nerve terminals via fast non-genomic mechanisms putatively involving the activation of membrane-bound corticosteroid receptors. Facilitation of Glu release strengthen previous assumptions that MP may act as a cognitive enhancer in rats, while crosstalk with ATP-sensitive P2X7 receptors may promote a therapeutically desirable GABAergic inhibitory control during paroxysmal epileptic crisis that might be particularly relevant when extracellular Ca 2+ levels decrease below the threshold required for transmitter release.

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“…In addition, P2X7Rs regulate gliotransmitter release. P2X7Rs may increase the exocytosis ratio of glutamate/ GABA in a Ca 2+ -dependent manner in rat cortical nerve terminals, which contributes to the development of seizures [37].…”

Section: Atp/p2x7r Pathwaymentioning

confidence: 99%

The role of inflammation in epileptogenesis

Meng

Yao

2020

Acta Epileptologica

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Epilepsy is a chronic neurological disorder that has an extensive impact on a patient’s life. Accumulating evidence has suggested that inflammation participates in the progression of spontaneous and recurrent seizures. Pro-convulsant incidences can stimulate immune cells, augment the release of pro-inflammatory cytokines, elicit neuronal excitation as well as blood-brain barrier (BBB) dysfunction, and finally trigger the generation or recurrence of seizures. Understanding the pathogenic roles of inflammatory mediators, including inflammatory cytokines, cells, and BBB, in epileptogenesis will be beneficial for the treatment of epilepsy. In this systematic review, we performed a literature search on the PubMed database using the following keywords: “epilepsy” or “seizures” or “epileptogenesis”, and “immunity” or “inflammation” or “neuroinflammation” or “damage-associated molecular patterns” or “cytokines” or “chemokines” or “adhesion molecules” or “microglia” or “astrocyte” or “blood-brain barrier”. We summarized the classic inflammatory mediators and their pathogenic effects in the pathogenesis of epilepsy, based on the most recent findings from both human and animal model studies.

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Under stressful conditions activation of the ionotropic P2X7 receptor differentially regulates GABA and glutamate release from nerve terminals of the rat cerebral cortex

Cited by 19 publications

References 52 publications

The Role of NMDA Receptors in the Effect of Purinergic P2X7 Receptor on Spontaneous Seizure Activity in WAG/Rij Rats With Genetic Absence Epilepsy

The Role of NMDA Receptors in the Effect of Purinergic P2X7 Receptor on Spontaneous Seizure Activity in WAG/Rij Rats With Genetic Absence Epilepsy

Non-genomic Actions of Methylprednisolone Differentially Influence GABA and Glutamate Release From Isolated Nerve Terminals of the Rat Hippocampus

The role of inflammation in epileptogenesis

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