Epilepsy, as a chronic disorder characterized by neuronal dysfunctions and by substantial disturbances of glial cells. Dr Evgenia Sitnikova, together with colleagues from Istanbul University and Acibadem Mehmet Ali Aydinlar University (Istanbul, Turkey), published a review on the role of neuroglia in epilepsy, including epileptogenesis and ictogenesis, including epileptogenesis (generation of seizure activity) and ictogenesis (generating seizure activity).
Special attention is paid to new strategies for targeted therapy of epilepsy aimed at regulating the functions of astrocytic neuroglia: (1) selective targeting of glia-related molecular mechanisms of glutamate transport; (2) modulation of tonic GABA release from astrocytes; (3) gliotransmission; (4) targeting the astrocytic Kir4.1-BDNF system; (5) astrocytic Na+/K+/ATPase activity; (6) targeting DNA hypo- or hypermethylation of candidate genes in astrocytes; (7) targeting astrocytic gap junction regulators; (8) targeting astrocytic adenosine kinase (the major adenosine-metabolizing enzyme); and (9) targeting microglia-astrocyte communication and inflammatory pathways. Details could be found in this paper [1] published in July 2023 in Frontiers in Molecular Neuroscience
1. Carcak N., Onat F., Sitnikova E. Astrocytes as a target for therapeutic strategies in epilepsy: current insights. Frontiers In Molecular Neuroscience. 2023. 16: 1183775. DOI: 10.3389/fnmol.2023.1183775
The illustration [1] published licensed under CC BY 4.0. © 2023 authors
The mother's diet during the perinatal period is the most important early environmental factor that, through epigenetic modifications, can cause changes in gene expression and, as a consequence, the phenotype of the offspring. Employees of the Institute of Higher Inspectorate and Scientific Branch of the Russian Academy of Sciences and the Institute of Molecular Genetics of the Russian Academy of Sciences were the first to show that increased DNA methylation in the early stages of ontogenesis using a maternal diet enriched with methyl supplements (MAD) suppresses the manifestation of genetic absence epilepsy and comorbid depression in the offspring of WAG/Rij rats . The beneficial phenotypic effect of maternal MOD was accompanied by increased expression of pathogenetically significant genes - the hcn1 ion channel gene and the DNA methyltransferase 1 (dnmt1) gene in the somatosensory cortex and hippocampus, as well as the hcn1, dnmt1 and tyrosine hydroxylase (th) genes in the nucleus accumbens. The therapeutic effect of maternal MOD was similar to that of ethosuximide, the first-choice drug for the treatment of absence epilepsy. It is assumed that maternal MOD can serve as a new preventive therapeutic strategy for epigenetic correction of absence epilepsy and comorbid depression in offspring.
Статья опубликована в январе 2023 года в журнале Diagnostics:
https://doi.org/10.3390/diagnostics13030398
There are two main types of adrenergic receptors (alpha and beta) with several subtypes in the human and animal brain. Alpha2-adrenergic receptors are of particular interest, because they are involved in the modulation of sleep and absence epilepsy. In 2023, a group of young scientists led by a senior researcher, Dr. Evgenia Sitnikova, have studied the adrenergic mechanisms of sleep and epilepsy. The results of their research were published in the International Journal of Molecular Science and Frontiers in Neurology [1, 2, 3]. Therapeutic doses of alpha2 adrenergic agonists (such as dexmedetomidine) are known to cause sedation and drug-induced sleep in humans and animals. These drugs in low doses were found to induce spike-wave activity in the electroencephalogram, i.e. manifestation of absence epilepsy, in genetically prone rats (WAG/Rij) [1, 2, 3]. А single (intraperitoneal) injection of dexmedetomidine at the dose of 0.005 mg/kg increased absence epilepsy in WAG/Rij rats (i.e., genetic model of absence epilepsy) up to status epilepticus in subjects with severe absence epilepsy, but did not cause de novo absence epilepsy in asymptomatic rats [1, 2]. Dexmedetomidine has been regularly used in clinical practice for decades, and low doses of this drug may help in the diagnosis of latent forms of absence epilepsy during EEG examination. Dexmedetomidine, along with other central alpha2-adrenergic agonists, could be a pharmacological tool for differential diagnosis. The high risk of provoking absence status should be taken into account when using alpha2-adrenergic receptor agonists in patients with absence epilepsy or with a genetic predisposition to this disease [1].
A new concept of targeted pharmacotherapy of absence epilepsy using alpha2B-adrenergic receptor antagonists was proposed based on our experimental and literature data [1, 3].
- Sitnikova E. Adrenergic mechanisms of absence status epilepticus Front. Neurol. 2023 14: 1298310. DOI: 10.3389/fneur.2023.1298310
- Sitnikova E., Pupikina M., Rutskova E. Alpha2 Adrenergic Modulation of Spike-Wave Epilepsy: Experimental Study of Pro-Epileptic and Sedative Effects of Dexmedetomidine. International Journal of Molecular Sciences. 2023. 24(11): 9445. DOI: 10.3390/ijms24119445 .
- Sitnikova E., Rutskova E., Smirnov K. Alpha2-Adrenergic Receptors as a Pharmacological Target for Spike-Wave Epilepsy. International Journal of Molecular Sciences. 2023. 24(2):1477. DOI: 10.3390/ijms24021477.
The illustration [3] licensed under CC BY 4.0. © 2023 authors
Two main types of adrenergic receptors (alpha and beta) and many subtypes have been described in the human and animal brain. Alpha2-adrenergic receptors deserve special attention because they are involved in the modulation of sleep and absence epilepsy. In 2023, a group of young scientists under the guidance of a senior mentor, Dr. Sc. E.Yu. Sitnikova began research on the adrenergic mechanisms of sleep and epilepsy, the results of which were published in the International Journal of Molecular Science and Frontiers in Neurology [1, 2, 3]. Therapeutic doses of alpha2-adrenergic agonists (eg, dexmedetomidine) are known to have a sedative effect and induce drug-induced sleep in humans and animals. These drugs in low doses cause generalized peak-wave activity on the electroencephalogram, i.e. manifestation of absence epilepsy in rats with a genetic predisposition to this disease (WAG/Rij) [1, 2, 3]. Thus, a single injection of dexmedetomidine at a dose of about 0.005 mg/kg increased absence epilepsy in WAG/Rij rats (a genetic model of absence epilepsy) up to the onset of status epilepticus in individuals with severe absence epilepsy [2], but did not cause absence epilepsy. de novo epilepsy in asymptomatic rats [1, 2]. Dexmedetomidine is regularly used in clinical practice, and can be used in low doses to diagnose latent forms of absence epilepsy [1]. The high risk of provoking absence status should be taken into account when using alpha2-adrenergic receptor agonists in patients with absence epilepsy or with a genetic predisposition to this disease [1].
Based on an analysis of our own and literature data, a new concept of targeted pharmacotherapy of absence epilepsy using alpha2B-adrenergic receptor antagonists was put forward [1, 3].
- Sitnikova E. Adrenergic mechanisms of absence status epilepticus Front. Neurol. 2023 14: 1298310. DOI: 10.3389/fneur.2023.1298310
- Sitnikova E., Pupikina M., Rutskova E. Alpha2 Adrenergic Modulation of Spike-Wave Epilepsy: Experimental Study of Pro-Epileptic and Sedative Effects of Dexmedetomidine. International Journal of Molecular Sciences. 2023. 24(11): 9445. DOI: 10.3390/ijms24119445 .
- Sitnikova E., Rutskova E., Smirnov K. Alpha2-Adrenergic Receptors as a Pharmacological Target for Spike-Wave Epilepsy. International Journal of Molecular Sciences. 2023. 24(2):1477. DOI: 10.3390/ijms24021477.
Использована иллюстрация [3] с разрешения авторов под лицензией CC BY 4.0. © 2023