Synaptic Dysfunction in Epilepsy

Zaitsev, Aleksey V.; Amakhin, Dmitry V.; Dyomina, A. V.; Захарова, М. В.; Ergina, Julia L.; Postnikova, Tatyana Y.; Diespirov, Georgy P.; Magazanik, L. G.

doi:10.1134/s002209302103008x

Cited by 11 publications

(5 citation statements)

References 177 publications

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“…Rapid changes in synaptic function are often observed after an epileptic seizure [ 47 ]. It can be hypothesized that the transient downregulation of CP-AMPA receptors may be a compensatory mechanism that helps to minimize the consequences of seizures and results in a lack of transition to acquired epilepsy in the model of FS.…”

Section: Discussionmentioning

confidence: 99%

Febrile Seizures Cause a Rapid Depletion of Calcium-Permeable AMPA Receptors at the Synapses of Principal Neurons in the Entorhinal Cortex and Hippocampus of the Rat

Postnikova

Griflyuk

Zhigulin

et al. 2023

IJMS

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Febrile seizures (FSs) are a relatively common early-life condition that can cause CNS developmental disorders, but the specific mechanisms of action of FS are poorly understood. In this work, we used hyperthermia-induced FS in 10-day-old rats. We demonstrated that the efficiency of glutamatergic synaptic transmission decreased rapidly after FS by recording local field potentials. This effect was transient, and after two days there were no differences between control and post-FS groups. During early ontogeny, the proportion of calcium-permeable (CP)-AMPA receptors in the synapses of the principal cortical and hippocampal neurons is high. Therefore, rapid internalization of CP-AMPA receptors may be one of the mechanisms underlying this phenomenon. Using the whole-cell patch-clamp method and the selective CP-AMPA receptor blocker IEM-1460, we tested whether the proportion of CP-AMPA receptors changed. We have demonstrated that FS rapidly reduces synaptic CP-AMPA receptors in both the hippocampus and the entorhinal cortex. This process was accompanied by a sharp decrease in the calcium permeability of the membrane of principal neurons, which we revealed in experiments with kainate-induced cobalt uptake. Our experiments show that FSs cause rapid changes in the function of the glutamatergic system, which may have compensatory effects that prevent excessive excitotoxicity and neuronal death.

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Section: Discussionmentioning

confidence: 99%

Febrile Seizures Cause a Rapid Depletion of Calcium-Permeable AMPA Receptors at the Synapses of Principal Neurons in the Entorhinal Cortex and Hippocampus of the Rat

Postnikova

Griflyuk

Zhigulin

et al. 2023

IJMS

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“…These data were also confirmed in this model by other researchers [ 35 , 36 , 37 , 38 ]. Thus, epileptogenesis is closely linked to abnormalities in the glutamatergic system [ 39 ]. However, severe side effects caused by NMDA receptor blockers limit the use of such drugs in the clinic.…”

Section: Discussionmentioning

confidence: 99%

Changes in Metabotropic Glutamate Receptor Gene Expression in Rat Brain in a Lithium–Pilocarpine Model of Temporal Lobe Epilepsy

Коваленко

Захарова

Schwarz

et al. 2022

IJMS

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Preventing epileptogenesis in people at risk is an unmet medical need. Metabotropic glutamate receptors (mGluRs) are promising targets for such therapy. However, drugs acting on mGluRs are not used in the clinic due to limited knowledge of the involvement of mGluRs in epileptogenesis. This study aimed to analyze the changes in gene expression of mGluR subtypes (1–5, 7, 8) in various rat brain regions in the latent and chronic phases of a lithium–pilocarpine model of epilepsy. For this study, multiplex test systems were selected and optimized to analyze mGluR gene expression using RT-qPCR. Region- and phase-specific changes in expression were revealed. During the latent phase, mGluR5 mRNA levels were increased in the dorsal and ventral hippocampus, and expression of group III genes was decreased in the hippocampus and temporal cortex, which could contribute to epileptogenesis. Most of the changes in expression detected in the latent stage were absent in the chronic stage, but mGluR8 mRNA production remained reduced in the hippocampus. Moreover, we found that gene expression of group II mGluRs was altered only in the chronic phase. The study deepened our understanding of the mechanisms of epileptogenesis and suggested that agonists of group III mGluRs are the most promising targets for preventing epilepsy.

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“…Epileptic seizures significantly affect the functioning of synapses, and alterations have been described at the level of the post- and presynapse, as well as disturbances in the functioning of microglia and astrocytes [ 50 ]. One of the most serious consequences of PTZ-induced seizures detected in this study is impaired LTP.…”

Section: Discussionmentioning

confidence: 99%

Delayed Impairment of Hippocampal Synaptic Plasticity after Pentylenetetrazole-Induced Seizures in Young Rats

Postnikova

Trofimova

Захарова

et al. 2022

IJMS

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Data on the long-term consequences of a single episode of generalized seizures in infants are inconsistent. In this study, we examined the effects of pentylenetetrazole-induced generalized seizures in three-week-old rats. One month after the seizures, we detected a moderate neuronal loss in several hippocampal regions: CA1, CA3, and hilus, but not in the dentate gyrus. In addition, long-term synaptic potentiation (LTP) was impaired. We also found that the mechanism of plasticity induction was altered: additional activation of metabotropic glutamate receptors (mGluR1) is required for LTP induction in experimental rats. This disturbance of the plasticity induction mechanism is likely due to the greater involvement of perisynaptic NMDA receptors compared to receptors located in the core part of the postsynaptic density. This hypothesis is supported by experiments with selective blockades of core-located NMDA receptors by the use-dependent blocker MK-801. MK-801 had no effect on LTP induction in experimental rats and suppressed LTP in control animals. The weakening of the function of core-located NMDA receptors may be due to the disturbed clearance of glutamate from the synaptic cleft since the distribution of the astrocytic glutamate transporter EAAT2 in experimental animals was found to be altered.

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Synaptic Dysfunction in Epilepsy

Cited by 11 publications

References 177 publications

Febrile Seizures Cause a Rapid Depletion of Calcium-Permeable AMPA Receptors at the Synapses of Principal Neurons in the Entorhinal Cortex and Hippocampus of the Rat

Febrile Seizures Cause a Rapid Depletion of Calcium-Permeable AMPA Receptors at the Synapses of Principal Neurons in the Entorhinal Cortex and Hippocampus of the Rat

Changes in Metabotropic Glutamate Receptor Gene Expression in Rat Brain in a Lithium–Pilocarpine Model of Temporal Lobe Epilepsy

Delayed Impairment of Hippocampal Synaptic Plasticity after Pentylenetetrazole-Induced Seizures in Young Rats

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