Of the Mechanisms of Paroxysmal Depolarization Shifts: Generation and Maintenance of Bicuculline-Induced Paroxysmal Activity in Rat Hippocampal Cell Cultures

Laryushkin, Denis P.; Maiorov, S. A.; Зинченко, В. П.; Mal’tseva, V. N.; Gaidin, Sergei G.; Kosenkov, Artem M.

doi:10.3390/ijms241310991

Cited by 5 publications

(2 citation statements)

References 36 publications

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“…Neuron-glial cell cultures were prepared as described previously ( Gaidin et al, 2020 , 2023 ; Maiorov et al, 2021 ; Laryushkin et al, 2023 ). Wistar pups (P0-2) were euthanized with deep-inhaled anesthesia and decapitated.…”

Section: Methodsmentioning

confidence: 99%

“…To identify GABAergic and non-GABAergic neurons (glutamatergic), cell cultures were fixed and stained with antibodies against glutamate decarboxylase GAD 65/67 and neuron-specific enolase (NSE) after vital [Ca 2+ ] i imaging. The detailed protocol of immunostaining was described previously ( Maiorov et al, 2021 ; Laryushkin et al, 2023 ). A marker grid with a square side of approximately 3 mm was drawn on the bottom of the coverslips with the Fura-2-stained cell cultures before the vital fluorescent imaging experiments.…”

Section: Methodsmentioning

confidence: 99%

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Participation of calcium-permeable AMPA receptors in the regulation of epileptiform activity of hippocampal neurons

Zinchenko,

Teplov,

Kosenkov

et al. 2024

Front. Synaptic Neurosci.

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IntroductionEpileptiform activity is the most striking result of hyperexcitation of a group of neurons that can occur in different brain regions and then spread to other sites. Later it was shown that these rhythms have a cellular correlate in vitro called paroxysmal depolarization shift (PDS). In 13–15 DIV neuron-glial cell culture, inhibition of the GABA(A) receptors induces bursts of action potential in the form of clasters PDS and oscillations of intracellular Ca2+ concentration ([Ca2+]i). We demonstrate that GABAergic neurons expressing calcium-permeable AMPA receptors (CP-AMPARs) as well as Kv7-type potassium channels regulate hippocampal glutamatergic neurons’ excitability during epileptiform activity in culture.MethodsA combination of whole-cell patch-clamp in current clamp mode and calcium imaging microscopy was used to simultaneously register membrane potential and [Ca2+]i level. To identify GABAergic cell cultures were fixed and stained with antibodies against glutamate decarboxylase GAD 65/67 and neuron-specific enolase (NSE) after vital [Ca2+]i imaging.Results and discussionIt was shown that CP-AMPARs are involved in the regulation of the PDS clusters and [Ca2+]i pulses accompanied them. Activation of CP-AMPARs of GABAergic neurons is thought to cause the release of GABA, which activates the GABA(B) receptors of other GABAergic interneurons. It is assumed that activation of these GABA(B) receptors leads to the release of beta-gamma subunits of Gi protein, which activate potassium channels, resulting in hyperpolarization and inhibition of these interneurons. The latter causes disinhibition of glutamatergic neurons, the targets of these interneurons. In turn, the CP-AMPAR antagonist, NASPM, has the opposite effect. Measurement of membrane potential in GABAergic neurons by the patch-clamp method in whole-cell configuration demonstrated that NASPM suppresses hyperpolarization in clusters and individual PDSs. It is believed that Kv7-type potassium channels are involved in the control of hyperpolarization during epileptiform activity. The blocker of Kv7 channels, XE 991, mimicked the effect of the CP-AMPARs antagonist on PDS clusters. Both drugs increased the duration of the PDS cluster. In turn, the Kv7 activator, retigabine, decreased the duration of the PDS cluster and Ca2+ pulse. In addition, retigabine led to deep posthyperpolarization at the end of the PDS cluster. The Kv7 channel is believed to be involved in the formation of PDS, as the channel blocker reduced the rate of hyperpolarization in the PDS almost three times. Thus, GABAergic neurons expressing CP-AMPARs, regulate the membrane potential of innervated glutamatergic neurons by modulating the activity of postsynaptic potassium channels of other GABAergic neurons.

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Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Participation of calcium-permeable AMPA receptors in the regulation of epileptiform activity of hippocampal neurons

Zinchenko,

Teplov,

Kosenkov

et al. 2024

Front. Synaptic Neurosci.

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Role of inflammasomes and neuroinflammation in epilepsy

Hollis,

Lukens

2024

Immunological Reviews

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SummaryEpilepsy is a brain disorder characterized by recurrent seizures, which are brief episodes of abnormal electrical activity in the brain and involuntary movement that can lead to physical injury and loss of consciousness. Seizures are canonically accompanied by increased inflammatory cytokine production that promotes neuroinflammation, brain pathology, and seizure propagation. Understanding the source of pro‐inflammatory cytokines which promote seizure pathogenesis could be a gateway to precision epilepsy drug design. This review discusses the inflammasome in epilepsy including its role in seizure propagation and negative impacts on brain health. The inflammasome is a multiprotein complex that coordinates IL‐1β and IL‐18 production in response to tissue damage, cellular stress, and infection. Clinical evidence for inflammasome signaling in epileptogenesis is reviewed followed by a discussion of emerging strategies to modulate inflammasome activity in epilepsy.

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The role of the endocannabinoid system in the pathogenesis and treatment of epilepsy

Kosenkov,

Mal’tseva,

Maiorov

et al. 2024

Reviews in the Neurosciences

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Epilepsy is a group of chronic neurological brain disorders characterized by recurrent spontaneous unprovoked seizures, which are accompanied by significant neurobiological, cognitive, and psychosocial impairments. With a global prevalence of approximately 0.5–1 % of the population, epilepsy remains a serious public health concern. Despite the development and widespread use of over 20 anticonvulsant drugs, around 30 % of patients continue to experience drug-resistant seizures, leading to a substantial reduction in quality of life and increased mortality risk. Given the limited efficacy of current treatments, exploring new therapeutic approaches is critically important. In recent years, Gi-protein-coupled receptors, particularly cannabinoid receptors CB1 and CB2, have garnered increasing attention as promising targets for the treatment seizures and prevention of epilepsy. Emerging evidence suggests a significant role of the cannabinoid system in modulating neuronal activity and protecting against hyperexcitability, underscoring the importance of further research in this area. This review provides up-to-date insights into the pathogenesis and treatment of epilepsy, with a special focus on the role of the cannabinoid system, highlighting the need for continued investigation to develop more effective therapeutic strategies.

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Of the Mechanisms of Paroxysmal Depolarization Shifts: Generation and Maintenance of Bicuculline-Induced Paroxysmal Activity in Rat Hippocampal Cell Cultures

Cited by 5 publications

References 36 publications

Participation of calcium-permeable AMPA receptors in the regulation of epileptiform activity of hippocampal neurons

Participation of calcium-permeable AMPA receptors in the regulation of epileptiform activity of hippocampal neurons

Role of inflammasomes and neuroinflammation in epilepsy

The role of the endocannabinoid system in the pathogenesis and treatment of epilepsy

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