Faster flux of neurotransmitter glutamate during seizure — Evidence from 13C-enrichment of extracellular glutamate in kainate rat model

Kanamori, Keiko

doi:10.1371/journal.pone.0174845

Cited by 11 publications

(10 citation statements)

References 66 publications

(144 reference statements)

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“…51 In the present study, the EAAC1, GLT-1, GLAST, glutaminase, and GS gene expression levels (relative to the control levels) were increased in the M1, and CA3 areas of the PTZ-treated group. This finding supports the idea that glutamate levels in both brain areas were increased following PTZ injection, 33 and all glutamate reuptake activity correlates (glutamate transporter synthesis) to function maximally. However, understanding the functional activity of transporters and their expression levels is pivotal for exploring the mechanisms of chronic epilepsy.…”

Section: Discussionsupporting

confidence: 87%

See 1 more Smart Citation

Differential effects of inhibitors of PTZ‐induced kindling on glutamate transporters and enzyme expression

Taspınar

Hacımüftüoğlu

Butuner

et al. 2021

Clin Exp Pharma Physio

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Epilepsy is a neurological disorder resulting from abnormal neuronal firing in the brain.Glutamate transporters and the glutamate-glutamine cycle play crucial roles in the development of seizures. In the present study, the correlation of epilepsy with glutamate transporters and enzymes was investigated. Herein, male Wistar rats were randomly allocated into four groups (six animals/group); 35 mg/kg pentylenetetrazole (PTZ) was used to induce a kindling model of epilepsy. Once the kindling model was established, animals were treated for 15 days with either valproic acid (VPA, 350 mg/kg) or ceftriaxone (CEF, 200 mg/kg) in addition to the control group receiving saline. After treatment, electrocorticography (ECoG) was performed to record the electrical activity of the cerebral cortex. The glutamate reuptake time (T 80 ) was also determined in situ using an in vivo voltammetry. The expression levels of glutamate transporters and enzymes in the M1 and CA3 areas of the brain were determined using a real-time polymerase chain reaction (RT-PCR). ECoG measurements showed that the mean spike number of the PTZ + VPA and PTZ + CEF groups was significantly lower (p < 0.05) than that of the PTZ group. Compared with the PTZ group, VPA or CEF treatment decreased the glutamate reuptake time (T 80 ). The expression levels of EAAC1, GLT-1, GLAST, glutamine synthetase (GS), and glutaminase were increased in the PTZ group. Treatment with VPA or CEF enhanced the expression levels of GLT-1, GLAST, EAAC1, and GS, whereas the glutaminase expression level was reduced.The current results suggest that VPA or CEF decreases seizure activity by increasing glutamate reuptake by upregulating GLT-1 and GLAST expression, implying a possible mechanism for treating epilepsy. Also, we have suggested a novel mechanism for the antiepileptic activity of VPA via decreasing glutaminase expression levels. To our knowledge, this is the first study to measure the glutamate reuptake time in situ during the seizure (i.e., real-time measurement).

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Section: Discussionsupporting

confidence: 87%

“…32 The extracellular [ 12 C + 13 C] glutamate concentration increased progressively in frequently seizing rats. 32,33 The increased levels might be attributed to malfunctioning and/or downregulation of glutamate transporters. 16 The clear advance of our study was to measure the activity of glutamate transporters in situ and in real-time.…”

Section: Discussionmentioning

confidence: 99%

Differential effects of inhibitors of PTZ‐induced kindling on glutamate transporters and enzyme expression

Taspınar

Hacımüftüoğlu

Butuner

et al. 2021

Clin Exp Pharma Physio

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“…Following recovery for 3 days, EEG monitoring was performed to evaluate the frequency and duration of EEG seizures. An EEG seizure was identified according to the definition of a period of consistent and repetitive changes in amplitude and frequency of electrical activity for at least 10 sec, which was different from interictal activity ( 17 ). Data were collected and analyzed using an acquisition system (Physical Signal Recorder RM6240; Chengdu Instrument Factory, Chengdu, China).…”

Section: Methodsmentioning

confidence: 99%

Ephrin‑b3 modulates hippocampal neurogenesis and the reelin signaling pathway in a pilocarpine‑induced model of epilepsy

Liu

Shu

et al. 2018

Int J Mol Med

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Ephrin-B3 is important in the regulation of cell proliferation, differentiation and migration via cell-cell contact, and can activate the reelin pathway during brain development. However, the effect of ephrin-B3 on hippocampal neurogenesis and the reelin pathway in epilepsy remains to be fully elucidated. In the present study, the expression of ephrin-B3 in pilocarpine-induced status epilepticus (SE) rats was investigated. SYBR Green-based reverse transcription-quantitative polymerase chain reaction analysis, immunohistochemical labeling and western blot analysis were used to detect the gene and protein expression levels of ephrin-B3 and reelin pathway proteins. Immunofluorescence staining of doublecortin (DCX) was utilized to analyze hippocampal neurogenesis. The data revealed that the mRNA and protein expression levels of ephrin-B3 in the hippocampus decreased during the spontaneous seizure period. Of note, the expression of reelin and its downstream phosphorylation disabled 1 (p-Dab1) were also notably decreased during the spontaneous seizure period, which showed similar dynamic changes as in the expression of ephrin-B3. In addition, it was found that the number of DCX-labeled neuronal progenitor cells was increased in the hippocampus following pilocarpine-induced SE. To further clarify the role of ephrin-B3 in neurogenesis and the reelin pathway in epilepsy, an exogenous ephrin-B3 clustering stimulator, EphB3-Fc, was infused into the bilateral hippocampus of the rats post-SE. Following EphB3-Fc injection, it was found that the expression levels of reelin and p-Dab1 were significantly increased in the epileptic rats following EphB3-Fc injection. The number of DCX-labeled neuronal progenitor cells was reduced in the hippocampus of the epileptic rats. Furthermore, the intensity and frequency of spontaneous recurrent seizures and electroencephalographic seizures were attenuated in the epileptic rats post-injection. These results demonstrated the critical role of ephrin-B3 in regulation of the reelin pathway and hippocampal neurogenesis in epilepsy, providing experimental evidence that ephrin-B3 functions as a potential protective factor in epilepsy, at least in animals.

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“…Several microdialysis and microperfusion electrodes have been designed and tested to tackle the in vivo sensing challenge of simultaneously measuring changes in biomarkers during passive electrophysiological recording or active electrical stimulation of brain tissue [16,[95][96][97][98][99][100][101][102][103][104][105]. Some of the more elementary designs involve two separate probes for neurochemical sampling and EEG recording [95,96,102,104,[106][107][108][109][110][111][112][113][114]. Other designs successfully incorporate both technologies into a single probe [98][99][100][101]103] or even fix separate probes together through various means [115][116][117][118][119][120][121].…”

Section: Previously Fabricated Microdialysis and Microperfusion Electrode Systemsmentioning

confidence: 99%

Microdialysis and microperfusion electrodes in neurologic disease monitoring

Stangler

Kouzani

Bennet

et al. 2021

Fluids Barriers CNS

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Contemporary biomarker collection techniques in blood and cerebrospinal fluid have to date offered only modest clinical insights into neurologic diseases such as epilepsy and glioma. Conversely, the collection of human electroencephalography (EEG) data has long been the standard of care in these patients, enabling individualized insights for therapy and revealing fundamental principles of human neurophysiology. Increasing interest exists in simultaneously measuring neurochemical biomarkers and electrophysiological data to enhance our understanding of human disease mechanisms. This review compares microdialysis, microperfusion, and implanted EEG probe architectures and performance parameters. Invasive consequences of probe implantation are also investigated along with the functional impact of biofouling. Finally, previously developed microdialysis electrodes and microperfusion electrodes are reviewed in preclinical and clinical settings. Critically, current and precedent microdialysis and microperfusion probes lack the ability to collect neurochemical data that is spatially and temporally coincident with EEG data derived from depth electrodes. This ultimately limits diagnostic and therapeutic progress in epilepsy and glioma research. However, this gap also provides a unique opportunity to create a dual-sensing technology that will provide unprecedented insights into the pathogenic mechanisms of human neurologic disease.

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Faster flux of neurotransmitter glutamate during seizure — Evidence from 13C-enrichment of extracellular glutamate in kainate rat model

Cited by 11 publications

References 66 publications

Differential effects of inhibitors of PTZ‐induced kindling on glutamate transporters and enzyme expression

Differential effects of inhibitors of PTZ‐induced kindling on glutamate transporters and enzyme expression

Ephrin‑b3 modulates hippocampal neurogenesis and the reelin signaling pathway in a pilocarpine‑induced model of epilepsy

Microdialysis and microperfusion electrodes in neurologic disease monitoring

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