Changes in Functional Properties of Rat Hippocampal Neurons Following Pentylenetetrazole-induced Status Epilepticus

Postnikova, Tatyana Y.; Amakhin, Dmitry V.; Trofimova, Alina M.; Smolensky, Ilya V.; Zaitsev, Aleksey V.

doi:10.1016/j.neuroscience.2018.12.029

Cited by 24 publications

(28 citation statements)

References 57 publications

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“…Next, to determine whether the efficacy of synaptic transmission changed after CTX treatment, the input/output (I/O) relationship between the fEPSP and FV amplitudes was determined for each slice (Figure 3d) and fitted with a sigmoidal Gompertz function (Equation (1)). The maximum slope of this fit reflected the composite cellular transfer function between the presynaptic action potentials and postsynaptic membrane response [43]. Therefore, the maximal I/O slope may be considered a measure of synaptic strength.…”

Section: Resultsmentioning

confidence: 99%

Ceftriaxone Treatment Affects EAAT2 Expression and Glutamatergic Neurotransmission and Exerts a Weak Anticonvulsant Effect in Young Rats

Zaitsev

Malkin

Postnikova

et al. 2019

IJMS

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Epilepsy is a common neurological disorder. Despite the availability of a wide range of antiepileptic drugs, these are unsuccessful in preventing seizures in 20–30% of patients. Therefore, new pharmacological strategies are urgently required to control seizures. Modulation of glutamate uptake may have potential in the treatment of pharmacoresistant forms of epilepsy. Previous research showed that the antibiotic ceftriaxone (CTX) increased the expression and functional activity of excitatory amino acid transporter 2 (EAAT2) and exerted considerable anticonvulsant effects. However, other studies did not confirm a significant anticonvulsant effect of CTX administration. We investigated the impacts of CTX treatment on EAAT expression and glutamatergic neurotransmission, as well its anticonvulsant action, in young male Wistar rats. As shown by a quantitative real-time polymerase chain reaction (qPCR) assay and a Western blot analysis, the mRNA but not the protein level of EAAT2 increased in the hippocampus following CTX treatment. Repetitive CTX administration had only a mild anticonvulsant effect on pentylenetetrazol (PTZ)-induced convulsions in a maximal electroshock threshold test (MEST). CTX treatment did not affect the glutamatergic neurotransmission, including synaptic efficacy, short-term facilitation, or the summation of excitatory postsynaptic potentials (EPSPs) in the hippocampus and temporal cortex. However, it decreased the field EPSP (fEPSP) amplitudes evoked by intense electrical stimulation. In conclusion, in young rats, CTX treatment did not induce overexpression of EAAT2, therefore exerting only a weak antiseizure effect. Our data provide new insight into the effects of modulation of EAAT2 expression on brain functioning.

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Section: Resultsmentioning

confidence: 99%

Ceftriaxone Treatment Affects EAAT2 Expression and Glutamatergic Neurotransmission and Exerts a Weak Anticonvulsant Effect in Young Rats

Zaitsev

Malkin

Postnikova

et al. 2019

IJMS

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“…Under normal physiological conditions, the endogenous antioxidative system in the rat hippocampus can scavenge the normal production of free radicals (Atinga., et al, 2015). In the pathological state of PTZ-induced seizures, the overproduction of free radicals disturbs and destroys the antioxidative system and causes oxidative damage (Postnikova et al, 2019). By comparing the results from the PTZ+FA group and the PTZ group, it was demonstrated that FA reduced the level of seizures and prolonged the latency of seizures in a PTZ-induced seizure model.…”

Section: Discussionmentioning

confidence: 99%

“…Thus, the oxidation and the changes in the apoptotic indexes, together with the expression of Apaf-1, caspase-9, caspase-3, Bid, and cleaved caspase-3 were thoroughly investigated here. This study focuses on the hippocampus because 1 day after PTZ injection, the hippocampal neurons became more excitable (Postnikova et al, 2019), and 4 days after PTZ injection, rats' electroencephalography was affected, γ-Aminobutyric acid B receptor (GABABR) expression was decreased and neuronal apoptosis was induced in the hippocampal part of the brain (Naseer et al, 2013). Furthermore, prolonged and repeated seizures affected the viability and morphological changes of neurons in the hippocampus up to 1 week after PTZ treatment (Vasilev et al, 2018).…”

Section: Introductionmentioning

confidence: 99%

Ferulic acid ameliorates pentylenetetrazol-induced seizures by reducing neuron cell death

et al. 2019

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To investigate the neuroprotective effect of ferulic acid (FA) in a pentylenetetrazol (PTZ)induced seizures rat model, the seizures behaviour, spatial learning ability and memory capability of the rats were assessed. Both the antioxidation and anti-apoptosis pathways were also investigated. In this study, male Wistar rats were randomly divided into 3 groups (n = 12 in each group). For 28 days, the rats were administered saline alone (i.p. normal saline, NS group), PTZ (40 mg/kg, i.p., PTZ group) once daily to induce seizures, or FA (i.p. 60 mg/kg) 20 min before being given PTZ (40 mg/kg, i.p., FA + PTZ group) to assess the neuroprotective effect of FA. The seizures behaviour of the rats was analysed with the Racine scale. The spatial learning and memory capacity of the rats were assessed by the Morris water maze test. The superoxide dismutase (SOD) activity and malondialdehyde (MDA) content were measured, and both in situ staining with the DNA-binding bisbenzimide Hoechst 33258 and TUNEL assays were used to assess apoptosis. Western blotting was used to further analyse the expression of Apaf-1, caspase-9, caspase-3, Bcl-2, Bid, Bax, cleaved caspase-3 and cytochrome c. The results showed that compared to the those of the PTZ group, FA pre-treatment significantly (p < 0.01) reduced the Racine scores starting at day 4, prolonged the latency of the onset of seizure at day 28, reduced the escape latency period starting at day 2, increased the frequency of crossing the platform location, increased the SOD activity, reduced the MDA content and apoptosis rate, and upregulated the Bcl-2 levels whilst downregulating the Bax, cytochrome c, Apaf-1, caspase-9, caspase-3, cleaved caspase-3 and Bid expression levels. This study demonstrated that pre-treatment with FA exerts strong neuroprotective effects by reducing seizures behaviour and by improving spatial learning ability and memory capacity. The neuroprotective effect may be a result of a reduction in neuron cell death that occurs via the antioxidative and anti-apoptotic pathways.

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“…Seizures differentially affect different brain regions [21,27,33,34]. Loss of neurons and gliosis occurs in specific brain areas depending on the model used [35][36][37][38].…”

Section: Discussionmentioning

confidence: 99%

Reference Gene Validation in the Brain Regions of Young Rats after Pentylenetetrazole-Induced Seizures

et al. 2020

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Reverse transcription followed by quantitative polymerase chain reaction (qRT-PCR) is a powerful and commonly used tool for gene expression analysis. It requires the right choice of stably expressed reference genes for accurate normalization. In this work, we aimed to select the optimal reference genes for qRT-PCR normalization within different brain areas during the first week following pentylenetetrazole-induced seizures in immature (P20–22) Wistar rats. We have tested the expression stability of a panel of nine housekeeping genes: Actb, Gapdh, B2m, Rpl13a, Sdha, Ppia, Hprt1, Pgk1, and Ywhaz. Based on geometric averaging of ranks obtained by four common algorithms (geNorm, NormFinder, BestKeeper, Comparative Delta-Ct), we found that the stability of tested reference genes varied significantly between different brain regions. The expression of the tested panel of genes was very stable within the medial prefrontal and temporal cortex, and the dorsal hippocampus. However, within the ventral hippocampus, the entorhinal cortex and amygdala expression levels of most of the tested genes were not steady. The data revealed that in the pentylenetetrazole-induced seizure model in juvenile rats, Pgk1, Ppia, and B2m expression are the most stable within the medial prefrontal cortex; Ppia, Rpl13a, and Sdha within the temporal cortex; Pgk1, Ppia, and Rpl13a within the entorhinal cortex; Gapdh, Ppia, and Pgk1 within the dorsal hippocampus; Rpl13a, Sdha, and Ppia within the ventral hippocampus; and Sdha, Pgk1, and Ppia within the amygdala. Our data indicate the need for a differential selection of reference genes across brain regions, including the dorsal and ventral hippocampus.

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Changes in Functional Properties of Rat Hippocampal Neurons Following Pentylenetetrazole-induced Status Epilepticus

Cited by 24 publications

References 57 publications

Ceftriaxone Treatment Affects EAAT2 Expression and Glutamatergic Neurotransmission and Exerts a Weak Anticonvulsant Effect in Young Rats

Ceftriaxone Treatment Affects EAAT2 Expression and Glutamatergic Neurotransmission and Exerts a Weak Anticonvulsant Effect in Young Rats

Ferulic acid ameliorates pentylenetetrazol-induced seizures by reducing neuron cell death

Reference Gene Validation in the Brain Regions of Young Rats after Pentylenetetrazole-Induced Seizures

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