Annals of Clinical and Experimental NeurologyAnnals of Clinical and Experimental NeurologyАнналы клинической и экспериментальной неврологии2075-54732409-2533Eco-Vector55010.25692/ACEN.2018.4.8Original articlesОригинальные статьиUnknownThe sigma1 receptor agonist enhances long-term depression caused by activation of metabotropic glutamate receptors in rat hippocampal neuronsАгонист сигма1-рецепторов усиливает длительную депрессию, вызванную активацией метаботропных глутаматных рецепторов в нейронах гиппокампа крысыRogozinPavel D.РогозинПавел Денисович
Russian Federation
synaptology@mail.ruSolntsevaElena I.СолнцеваЕлена Ивановна
Russian Federation
synaptology@mail.ruSkrebitskyVladimir G.СкребицкийВладимир Георгиевич
Russian Federation
synaptology@mail.ruResearch Center of NeurologyФГБНУ «Научный центр неврологии»07122018124576113122018Copyright ©; 2018, Rogozin P.D., Solntseva E.I., Skrebitsky V.G.Copyright ©; 2018, Rogozin P.D., Solntseva E.I., Skrebitsky V.G.2018Rogozin P.D., Solntseva E.I., Skrebitsky V.G.Rogozin P.D., Solntseva E.I., Skrebitsky V.G.https://creativecommons.org/licenses/by/4.0https://annaly-nevrologii.com/pathID/article/view/550

Introduction. Metabotropic glutamate receptors of group 1 (mGluR1/5) are an important component of the hippocampal inhibitory system. Disturbances of their work lead to manifestation of various pathologies of the nervous system. The search for effective ways of regulating the work of mGluR1/5 is an urgent problem of neuropharmacology. In the present study, we assessed for the first time the possibility of modulating mGluR1/5 by activation of sigma1 receptors (Sig1-R), chaperone proteins capable of directly to directly interact with other proteins and to enhance their activity.

Objective. To study the effect of a specific Sig1-R agonist, PRE-084, on long-term depression of glutamate inputs in the hippocampus caused by activation of mGluR1/5.

Materials and methods. On slices of the hippocampus of rat brain in the CA1 region, population spikes (PS) caused by stimulation of Shaffer collaterals were registered. Activation of mGluR1/5 was induced by the application of 50 μM of specific agonist of these receptors, dihydroxyphenylglycine (DHPG), for 10 min. Activation of Sig1-R was induced by the application of 10 μM of specific agonist PRE-084 for 20 min.

Results. A short-term incubation of a rat hippocampal slice in a solution containing DHPG, caused a long-term depression of PS, so that within 30 min after the slice was washed away from the preparation, its amplitude was 60.0±14.4% of the control value (n=5). In the second series of experiments DHPG was applied against the background of the agonist Sig1-R PRE-084. PRE-084 was found to cause an increase in the inhibitory aftereffect of DHPG, so that the amplitude of the PS measured after 30 min after removal of the preparations from the surrounding solution was 16.0±1.7% (р<0.05).

Conclusion. It was shown for the first time that activation of Sig1-R enhances the functional activity of mGluR1/5.

Введение. Метаботропные глутаматные рецепторы группы 1 (mGluR1/5) являются важным компонентом тормозной системы гиппокампа. Нарушение их работы приводит к проявлению различных форм патологии нервной системы. Поиск эффективных способов регуляции работы mGluR1/5 является актуальной проблемой нейрофармакологии. В настоящей работе впервые была изучена возможность модуляции mGluR1/5 с помощью активации сигма1-рецепторов (Sig1-R) – белков-шаперонов, способных прямо взаимодействовать с другими белками и усиливать их активность.

Цель исследования: изучить воздействие специфического агониста Sig1-R – PRE-084 на эффект длительной депрессии глутаматных входов в гиппокампе, вызванный активацией mGluR1/5.

Материалы и методы. На срезах гиппокампа мозга крысы в области СА1 регистрировали популяционные спайки, вызванные стимуляцией коллатералей Шаффера. Активацию mGluR1/5 вызывали аппликацией 50 мкМ специфического агониста этих рецепторов дигидроксифенилглицина (DHPG) в течение 10 мин. Активацию Sig1-R вызывали аппликацией 10 мкМ специфического агониста PRE-084 в течение 20 мин.

Результаты. Кратковременная инкубация среза гиппокампа крысы в растворе, содержащем DHPG, вызывала длительную депрессию популяционных спайков, так что через 30 мин после отмывания среза от препарата его амплитуда составляла 60,0±14,4% от контрольной величины (n=5). PRE-084 усиливал тормозное последействие DHPG, и амплитуда популяционных спайков через 30 мин после устранения препаратов из окружающего срез раствора составляла 16,0±1,7% (р<0,05).

Заключение. Впервые показано, что активация Sig1-R усиливает функциональную активность mGluR1/5.

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