Decreased expression of hippocampal Na+/Ca2+ exchanger isoform-1 by pentylenetetrazole kindling in mice

Kawanai, Takuya; Taruta, Atsuki; Inoue, Aya; Watanabe, Ryoji; Ago, Yukio; Hashimoto, Hitoshi; Hasebe, Shigeru; Ooi, Yasuhiro; Takuma, Kazuhiro; Matsuda, Takehisa

doi:10.1016/j.eplepsyres.2015.06.002

Cited by 5 publications

(3 citation statements)

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“…In chronic epileptic adult rats, the expression of the NCX1 protein was decreased in the dentate gyrus and layer III of the EC; similarly, NCX3 protein expression was diminished in the stratum lucidum and hilar region of the dentate gyrus, and both reductions were permanent from 3 weeks until 2 months after the induction of status epilepticus by kainic acid and were closely related to neuronal death in the same regions [63]. Seizures induced by hyperthermia in young rats (PD20) have been related to downregulation of NCX3 expression in the Hp and cerebral cortex [68], while seizures induced by pentylenetetrazol in adult mice decrease NCX1 and NCX2 expression in the Hp without modifications in NCX3 expression [69]. In adult rats, ischaemia reduces the expression of NCX1 and NCX3 without affecting NCX2 in the temporoparietal cortex, but when ischaemic preconditioning or postconditioning are applied, the expression levels of NCX1 and NCX3 are augmented, with more significant effects at 24 h of reperfusion [70, 71].…”

Section: Discussionmentioning

confidence: 99%

“…NCX3 overexpression has been related to seizure resistance [73] and downregulation of seizure susceptibility [68, 73]. Evidence on the roles of NCX1 is contradictory, as NCX1 knock-out mice are resistant to seizures induced by pentylenetetrazole [74], but NCX1 downregulation has been related to epileptogenesis in a kindling model [69]. Here, even though MSG-treated rats show an augmented expression of NCX3 and NCX1, they are more susceptible to seizures induced by 4-AP [44], probably because the changes in the expression of NCXs are accompanied by a very broad and complex set of modifications [18, 25], including reductions in GABAergic inhibitory neurotransmission [14, 15].…”

Section: Discussionmentioning

confidence: 99%

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KB-R7943 reduces 4-aminopyridine-induced epileptiform activity in adult rats after neuronal damage induced by neonatal monosodium glutamate treatment

et al. 2017

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BackgroundNeonatal monosodium glutamate (MSG) treatment triggers excitotoxicity and induces a degenerative process that affects several brain regions in a way that could lead to epileptogenesis. Na+/Ca2+ exchangers (NCX1-3) are implicated in Ca2+ brain homeostasis; normally, they extrude Ca2+ to control cell inflammation, but after damage and in epilepsy, they introduce Ca2+ by acting in the reverse mode, amplifying the damage. Changes in NCX3 expression in the hippocampus have been reported immediately after neonatal MSG treatment. In this study, the expression level of NCX1-3 in the entorhinal cortex (EC) and hippocampus (Hp); and the effects of blockade of NCXs on the seizures induced by 4-Aminopyridine (4-AP) were analysed in adult rats after neonatal MSG treatment. KB-R7943 was applied as NCXs blocker, but is more selective to NCX3 in reverse mode.MethodsNeonatal MSG treatment was applied to newborn male rats at postnatal days (PD) 1, 3, 5, and 7 (4 g/kg of body weight, s.c.). Western blot analysis was performed on total protein extracts from the EC and Hp to estimate the expression level of NCX1-3 proteins in relative way to the expression of β-actin, as constitutive protein. Electrographic activity of the EC and Hp were acquired before and after intracerebroventricular (i.c.v.) infusion of 4-AP (3 nmol) and KB-R7943 (62.5 pmol), alone or in combination. All experiments were performed at PD60. Behavioural alterations were also recorder.ResultsNeonatal MSG treatment significantly increased the expression of NCX3 protein in both studied regions, and NCX1 protein only in the EC. The 4-AP-induced epileptiform activity was significantly higher in MSG-treated rats than in controls, and KB-R7943 co-administered with 4-AP reduced the epileptiform activity in more prominent way in MSG-treated rats than in controls.ConclusionsThe long-term effects of neonatal MSG treatment include increases on functional expression of NCXs (mainly of NCX3) in the EC and Hp, which seems to contribute to improve the control that KB-R7943 exerted on the seizures induced by 4-AP in adulthood. The results obtained here suggest that the blockade of NCXs could improve seizure control after an excitotoxic process; however, this must be better studied.Electronic supplementary materialThe online version of this article (doi:10.1186/s12929-017-0335-y) contains supplementary material, which is available to authorized users.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

KB-R7943 reduces 4-aminopyridine-induced epileptiform activity in adult rats after neuronal damage induced by neonatal monosodium glutamate treatment

et al. 2017

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“…Among the available seizure induction procedures, the use of proconvulsive drugs seems particularly suitable for this task as their administration can be precisely controlled and manipulated by, for example, supplying such drugs in appropriate concentrations and rates. Indeed, aiming to standardize the onset latency, duration, and number of tonic–clonic (TC) seizures in rats for seizure detection purposes , and for testing new anti‐convulsive therapies , we developed a method for controlled infusion of pentylenetetrazol (PTZ), which is one of the most used proconvulsive drugs . In those studies, we observed that the TC seizures were always preceded by brief episodes of spike‐and‐wave (SW) discharges occurring consistently at a PTZ dose of around 25 mg/kg.…”

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confidence: 99%

A New Rat Model of Seizures Suitable for Screening Antiepileptic Electrical Stimulation Therapies

et al. 2017

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Abstract:The antiepileptic effects of the electrical stimulation therapies developed for patients with intractable epilepsies depend critically on the stimulation parameters, including the pulse duration, current, and frequency. Consequently, optimization of such therapies requires many animals for testing each of the stimulation parameters alone or in combination, which is costly and time consuming. This drawback could be reduced by testing several stimulation paradigms in each animal, but this requires an animal model of long-lasting seizures allowing such repetitive tests. This study was performed to validate such a model of long-lasting seizures. The present analysis was performed on electrocorticogram and intracortical signals collected from the somatosensory cortex of 11 Sprague Dawley rats. A protocol of controlled intravenous infusion of pentylenetetrazol (PTZ) was developed to induce spikeand-wave (SW) seizures and maintain stable those seizures for the whole experimental time. SW discharges were induced and maintained stable for 2 h in all rats through a two-stage infusion of PTZ. During the first stage, the SW discharges were induced by 2.5 min infusion of 10 mg/kg/ min PTZ. During the second stage, the SW discharges were maintained at a stable level of frequency and power for 2 h via a 0.21 mg/kg/min PTZ infusion rate. The proposed animal model of seizures is characterized by SW discharges which remain stable for 2 h. This 2-h long time interval allows repetitive tests with different stimulation parameters in each animal, which may lead to a significant reduction of the number of animals necessary for optimizing electrical stimulation therapies developed to inhibit seizures. Key Words: Pentylenetetrazol-Spike-andwave-Seizures-Model.Although many animal models of seizures have been developed to date, establishing new such models of seizures is currently in focus (1-3) as seizure models that are more suitable for basic research purposes or for testing new antiepileptic therapies are still needed (4). For example, efforts are currently made for developing electrical stimulation therapies for patients with drug-resistant epilepsies. As studies have shown, the antiepileptic effects of such therapies depend critically on the stimulation parameters, such as the duration, current, and frequency of the applied electrical pulses (5-7). Consequently, optimization of these therapies requires many animals for testing the stimulation parameters alone or in the many possible combinations, which is costly and time consuming. This drawback could be minimized by reducing the number of animals necessary for performing such tests, which would also comply with the present ethical demands related to animal studies (8,9). One way to achieve this objective is by developing animal models of longlasting seizures to allow repetitive testing of several stimulation paradigms in each animal. However epilepsy seizures are typically transient episodes (10-12) and, therefore, developing models of longlasting seizures requires method...

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Intracellular calcium homeostasis and its dysregulation underlying epileptic seizures

Zhou

Chen

Lin

et al. 2022

Seizure: European Journal of Epilepsy

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Decreased expression of hippocampal Na+/Ca2+ exchanger isoform-1 by pentylenetetrazole kindling in mice

Cited by 5 publications

References 20 publications

KB-R7943 reduces 4-aminopyridine-induced epileptiform activity in adult rats after neuronal damage induced by neonatal monosodium glutamate treatment

KB-R7943 reduces 4-aminopyridine-induced epileptiform activity in adult rats after neuronal damage induced by neonatal monosodium glutamate treatment

A New Rat Model of Seizures Suitable for Screening Antiepileptic Electrical Stimulation Therapies

Intracellular calcium homeostasis and its dysregulation underlying epileptic seizures

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