vavilovВавиловский журнал генетики и селекцииVavilov Journal of Genetics and Breeding2500-3259Institute of Cytology and Genetics of Siberian Branch of the RAS10.18699/VJ18.401vavilov-1597Research ArticleРЕПРОДУКТИВНЫЕ ТЕХНОЛОГИИPHYSIOLOGICAL GENETICSРегуляция ацетилирования гистона Н4 в центральной нервной системе и командных нейронах оборонительного поведения моллюска Helix серотонином и нейропептидом FMRFамидомRegulation of histone H4 acetylation in the CNS and defensive behavior command neurons of the mollusk Helix mediated by serotonin and neuropeptide FMRFamideГринкевичЛ. Н.GrinkevichL. N.Larisa_Gr_spb@mail.ruЗачепилоТ. Г.ZachepiloT. G.Институт физиологии им. И.П. Павлова Российской академии наукРоссияPavlov Institute of Physiology, RASRussian Federation201809082018225606610Copyright © Гринкевич Л.Н., Зачепило Т.Г., 20182018Гринкевич Л.Н., Зачепило Т.Г.Grinkevich L.N., Zachepilo T.G.This work is licensed under a Creative Commons Attribution 4.0 License.https://vavilov.elpub.ru/jour/article/view/1597

Вовлеченность эпигенетических механизмов в формирование долго­временной памяти не вызывает сомнений. В настоящее время среди этих механизмов наиболее активно исследуются изменения уровня различных гистоновых модификаций (в первую очередь, ацетилирования и метилирования) в составе хроматина клеток центральной нервной системы (ЦНС) на различных экспериментальных моделях. Одна из наиболее удобных моделей – моллюски, их ЦНС относительно просто устроена и для ряда видов достаточно хорошо охарактеризо­вана. В работе в качестве объекта исследования использована ЦНС виноградной улитки (Helix lucorum), для которой ранее была выявлена группа нейронов, участвующих в формировании различных типов поведения, включая сохраняющийся во времени ответ на различные стимулы. Целью работы было изучение влияния известных эффекто­ров: серотонина и FMRFамида, связанных в ЦНС с активаторными и тормозными путями соответственно, на ацетилирование гистона Н4 в подглоточном комплексе ганглиев, а также в командных нейронах оборонительного поведения правого (ППа3/2) и левого (ЛПа3/2) париетальных ганглиев улитки. Исследование проводилось методом Вестерн-блот гибридизации. Полученные результаты указывают на сильную зависимость эффектов изучаемых нейромедиаторов от структур ЦНС, которые подвергались воздействию этих веществ. Так, оказалось, что в подглоточном комплексе ганглиев под действием се­ротонина происходило усиление суммарного ацетилирования гисто­на Н4, а FMRFамид подавлял его эффект. В противоположность этому, в командных нейронах правого париетального ганглия серотонин и FMRFамид усиливали действие друг друга, что приводило к суще­ственному повышению уровня ацетилирования гистона Н4. Однако в симметричных нейронах левого париетального ганглия никаких изменений в уровне ацетилирования под действием обоих веществ не наблюдалось, что служит новым свидетельством наличия функциональной асимметрии у Helix. Результаты исследования позволяют сделать заключение о двоякой роли тормозных путей, опосредуемых FMRFамидом, в зависимости от контекста нейрональных комплексов, они могут как подавлять действие активаторных путей, что было за­фиксировано нами в подглоточном комплексе ганглиев улитки, так и выступать в роли их синергистов, как в командных нейронах оборонительного поведения правого париетального ганглия.

Epigenetic mechanisms are commonly known to underlie memory formation. Presently, scientists’ attention is focused on changes in the levels of histone modifications (mainly acetylation and methylation) in the chromatin of CNS cells tested in various experimental models. Owing to their relatively simple CNSs, mollusks are among the most popular models. Our experiments were con-ducted with the mollusk Helix lucorum because its CNS had been investigated in detail and most of its neurons had been proven to participate in the formation of different behavior patterns, including the prolonged response to various stimuli. This work concerns the influence of various effectors (serotonin and FMRFamide, associated with CNS activator and inhibitory pathways, respectively) on the acetylation of H4 histone in the subesopha­geal ganglion complex and in defensive behavior command neurons of the right and left parietal ganglia (RPa3/2 and LPa3/2) in the snail. Western blot analysis showed that FMRFamide inhibited histone H4 acetylation induced by serotonin in the subesophageal complex of CNS ganglia. How­ever, serotonin and FMRFamide cooperatively enhanced the induction of histone H4 acetylation in RPa3/2 defensive behavior command neurons. No changes were found in the counterpart LPa3/2. It is a new piece of evidence for functional asym­metry in Helix. The inhibitory pathways mediated by FMRFamide not only inhibit the activatory in­tracellular processes in the entire CNS but can also enhance them, as in RPa3/2 defensive behavior command neurons.

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