kurskvestЧеловек и его здоровьеHumans and their health1998-57461998-5754Kursk State Medical University10.21626/vestnik/2020-3/09kurskvest-848Research ArticleМЕДИКО-БИОЛОГИЧЕСКИЕ НАУКИMEDICOBIOLOGICAL SCIENCESКоррекция нарушений нейрональных гомеостатических механизмов при нервно-психических заболеваниях как вероятное направление медикаментозного воздействияCorrection of disorders of neuronal homeostatic mechanisms in case of neuropsychiatric diseases as a probable direction of drug exposurehttps://orcid.org/0000-0002-2229-7541АбрамецИгорь ИгоревичAbrametsIgor I.

д-р мед. наук, профессор, профессор кафедры фармакологии и клинической фармакологии им. проф. И.В. Комиссарова

DM, Professor, Professor of the Department of Pharmacology and Clinical Pharmacology named after prof. I.V. Komissarov

abramets4141@mail.ruhttps://orcid.org/0000-0003-2989-7811ЕвдокимовДмитрий ВладимировичEvdokimovDmitriy V.

канд. мед. наук, доцент, доцент кафедры фармакологии и клинической фармакологии им. проф. И.В. Комиссарова

PhD in Medicine, Associate Professor, Associate Professor of the Department of Pharmacology and Clinical Pharmacology named after prof. I.V. Komissarov

evdokimov.dmit@yandex.ruhttps://orcid.org/0000-0002-8368-5644КузнецовЮрий ВасильевичKuznetsovYuriy V.

канд. мед. наук, доцент кафедры фармакологии и клинической фармакологии им. проф. И.В. Комиссарова

PhD in Medicine, Associate Professor of the Department of Pharmacology and Clinical Pharmacology named after prof. I.V. Komissarov

far6@yandex.ruhttps://orcid.org/0000-0002-9133-9952СидороваЮлия ВладимировнаSidorovaYuliya V.

канд. мед. наук, ассистент кафедры фармакологии и клинической фармакологии им. проф. И.В. Комиссарова

PhD in Medicine, Assistant of the Department of Pharmacology and Clinical Pharmacology named after prof. I.V. Komissarov

vanul@i.uaДонецкий национальный медицинский университет им. М. ГорькогоM. Gorkiy Donetsk National Medical University202021092021037283Copyright © Абрамец И.И., Евдокимов Д.В., Кузнецов Ю.В., Сидорова Ю.В., 20212021Абрамец И.И., Евдокимов Д.В., Кузнецов Ю.В., Сидорова Ю.В.Abramets I.I., Evdokimov D.V., Kuznetsov Y.V., Sidorova Y.V.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://www.kursk-vestnik.ru/jour/article/view/848

Совершенствование лекарственной терапии ряда нервно-психических заболеваний требует поиска новых направлений воздействия по сравнению с используемыми в настоящее время. Большинство используемых лекарств воздействуют на молекулярные мишени, которые модулируют межструктурные (межнейронные) взаимодействия. Воздействие на более глубинные процессы синаптического и нейронального гомеостаза может быть новым направлением лечения данных заболеваний. В этом обзоре рассмотрены механизмы гомеостатической пластичности синаптической передачи и электрической возбудимости нейронов, которые уравновешивают друг друга и стабилизируют работу нейронов и нейронных сетей. Первая разновидность гомеостатической пластичности регулируется внутриклеточной концентрацией Са2+ и активностью протеинкиназ, а вторая - плотностью потенциалозависимых ионных каналов в мембранах нейронов. Анализ литературных данных показывает, что при нервно-психических заболеваниях наблюдаются нарушения гомеостатической пластичности чаще в виде однонаправленных изменений синаптических влияний и электрической возбудимости нейронов. Так, преимущественно в доклинических исследованиях выявлено, что вызываемые стрессом депрессивные расстройства поведения у грызунов сопровождаются однонаправленным либо усилением (в пирамидных нейронах 2/3 слоев префронтальной коры), либо ослаблением (в нейронах 5 слоя) синаптического драйва и электрической возбудимости. Подобные нарушения гомеостатической пластичности наблюдали другие авторы в пирамидных нейронах дорсолатеральной префронтальной коры при шизофрении в зависимости от преобладания позитивной или негативной симптоматики. При хронической нейропатической боли выявлено повышение возбудимости периферических нейронов спинальных/тригеминальных ганглиев, нейронов дорсальных рогов, кортикальных нейронов и усиление приходящих синаптических влияний. Наблюдаемые нарушения сопровождались изменениями плотности ионных каналов в мембранах нейронов. Особенности распределения и биофизических свойств потенциалозависимых калиевых каналов позволяют рассматривать их как вероятную молекулярную мишень для коррекции нарушений гомеостатической пластичности.

The improvement of drug therapy for a number of neuropsychiatric diseases requires the search for new directions of action in comparison with those currently used. Most of the drugs used affect molecular targets that modulate interstructural (interneuronal) interactions. Influencing the deeper processes of synaptic and neuronal homeostasis may be a new direction in the treatment of these diseases. This review examines the mechanisms of homeostatic plasticity of synaptic transmission and electrical excitability of neurons, which balance each other and stabilize the functioning of neurons and neural networks. The first type of homeostatic plasticity is regulated by the intracellular Ca2+ concentration and the activity of protein kinases, and the second one - by membrane density of voltage-dependent ionic channels. Analysis of literature data shows that alterations in some neuro-psychiatric diseases reveal disorders of homeostatic plasticity more often in terms of monodirectional alterations of synaptic impacts and neuronal electrical excitability. Thus, mainly in preclinical studies, it was revealed that stress-induced depressive disorders of behavior are accompanied by a unidirectional increase in pyramidal neurons of 2/3 layers of the prefrontal cortex of rodents, or a weakening in neurons of the 5th layer of synaptic drive and electrical excitability. Similar disorders of homeostatic plasticity were observed by other authors in pyramidal neurons of the dorsolateral prefrontal cortex in schizophrenia, depending on the prevalence of positive or negative symptoms. In chronic neuropathic pain, an increase in the excitability of peripheral neurons of the spinal / trigeminal ganglia, neurons of the dorsal horns, and cortical neurons and an increase in incoming synaptic influences were revealed. The observed disturbances were accompanied by changes in the density of ion channels in neuronal membranes. The peculiarities of the distribution and biophysical properties of voltage-dependent potassium channels allow us to consider them as a probable molecular target for the correction of disorders of homeostatic plasticity.

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The authors declare that there are no conflicts of interest present.