Annals of Clinical and Experimental NeurologyAnnals of Clinical and Experimental NeurologyАнналы клинической и экспериментальной неврологии2075-54732409-2533Eco-Vector143410.17816/ACEN.1434VBPEQOOriginal articlesОригинальные статьиResearch ArticleMitochondrial fission as a target for supressing aberrant neuroplasticity and degeneration in the hippocampusДеление митохондрий как мишень для подавления аберрантной нейропластичности и дегенерации в гиппокампеhttps://orcid.org/0000-0001-5222-5322VoronkovDmitry N.ВоронковДмитрий Николаевич
Russian Federation

Cand. Sci. (Med.), senior researcher, Laboratory of neuromorphology

канд. мед. наук, с. н. с. лаб. нейроморфологии Института мозга

voronkov@neurology.ruhttps://orcid.org/0000-0002-2128-9056FedorovaEvgenia N.ФедороваЕвгения Николаевна
Russian Federation

junior researcher, Laboratory of neuromorphology, Russian Center of Neurology and Neuroscience, assistant, Department of morphology, Institute of Anatomy and Morphology named after Acad.Yu. M. Lopukhin

м. н. с. лаб. нейроморфологии Института мозга, ассистент каф. морфологии Института анатомии и морфологии им. акад. Ю.М. Лопухина

ewgenia.feodorowa2011@yandex.ruhttps://orcid.org/0009-0006-5653-5524PavlovaAnastasia K.ПавловаАнастасия Кирилловна
Russian Federation

research assistant, Laboratory of experimental pathology of nervous system and neuropharmacology

лаборант-исследователь лаб. экспериментальной патологии нервной системы и нейрофармакологии Института мозга

pav_nastasya@mail.ruhttps://orcid.org/0009-0003-5596-7630RyabovaMaria S.РябоваМария Сергеевна
Russian Federation

research assistant, Laboratory of neuromorphology

лаборант-исследователь лаб. нейроморфологии Института мозга

voronkov@neurology.ruhttps://orcid.org/0000-0001-7112-2556EgorovaAnna V.ЕгороваАнна Валериевна
Russian Federation

Cand. Sci. (Med.), researcher, Laboratory of neuromorphology, Associate Professor, Department of morphology, Institute of Anatomy and Morphology named after Acad. Yu. M. Lopukhin

канд. мед. наук, н. с. лаб. нейроморфологии Института мозга, доцент каф. морфологии Института анатомии и морфологии им. акад. Ю.М. Лопухина

av_egorova@bk.ruhttps://orcid.org/0000-0002-8689-0934StavrovskayaAlla V.СтавровскаяАлла Вадимовна
Russian Federation

Cand. Sci. (Biol.), Head, Laboratory of experimental pathology of nervous system and neuropharmacology Brain Institute

канд. биол. наук, зав. лаб. экспериментальной патологии нервной системы и нейрофармакологии Института мозга

alla_stav@mail.ruhttps://orcid.org/0000-0002-7471-3738PotapovIvan A.ПотаповИван Александрович
Russian Federation

junior researcher, Laboratory of experimental pathology of nervous system and neuropharmacology Brain Institute

м.н.с. лаб. экспериментальной патологии нервной системы и нейрофармакологии Института мозга

potapov.i.a@neurology.ruhttps://orcid.org/0000-0002-0552-6939SukhorukovVladimir S.СухоруковВладимир Сергеевич
Russian Federation

Dr. Sci. (Med.), Professor, Head, Laboratory of neuromorphology, Department of morphology, Institute of Anatomy and Morphology named after Acad. Yu. M. Lopukhin

д-р мед. наук, зав. лаб. нейроморфологии Института мозга, профессор каф. морфологии Института анатомии и морфологии им. акад. Ю.М. Лопухина

voronkov@neurology.ruRussian Center of Neurology and NeurosciencesРоссийский центр неврологии и нейронаукPirogov Russian National Research Medical UniversityРоссийский национальный исследовательский медицинский университет имени Н.И. Пирогова2512202519462742010202512112025Copyright ©; 2025, Voronkov D.N., Fedorova E.N., Pavlova A.K., Ryabova M.S., Egorova A.V., Stavrovskaya A.V., Potapov I.A., Sukhorukov V.S.Copyright ©; 2025, Воронков Д.Н., Федорова Е.Н., Павлова А.К., Рябова М.С., Егорова А.В., Ставровская А.В., Потапов И.А., Сухоруков В.С.2025Voronkov D.N., Fedorova E.N., Pavlova A.K., Ryabova M.S., Egorova A.V., Stavrovskaya A.V., Potapov I.A., Sukhorukov V.S.Воронков Д.Н., Федорова Е.Н., Павлова А.К., Рябова М.С., Егорова А.В., Ставровская А.В., Потапов И.А., Сухоруков В.С.https://creativecommons.org/licenses/by/4.0https://annaly-nevrologii.com/pathID/article/view/1434

Introduction. Mdivi-1, an inhibitor of mitochondrial fission, has neuroprotective potential and can modulate pathological neuroplasticity, which is of interest for developing pharmacological therapies for mesial temporal lobe epilepsy.

The aim of this study is to summarize the results of a series of experiments with mdivi-1 on a model of kainate-induced hippocampal damage and evaluate the prospects of modulating mitochondrial dynamics to suppress neurodegeneration and aberrant plasticity.

Materials and methods. Wistar rats received kainic acid injections into the hippocampus and mdivi-1 into the lateral cerebral ventricles. Immunomorphological assessment included evaluation of proliferation and differentiation (using BrdU), maturation and damage of granule layer hippocampal neurons (assessing numbers of NeuN- and DCX-positive cells), glial reaction, and changes in mitochondrial dynamics (dynamin-related protein and mitofusin 2). The animals’ ability for novel object recognition and response to photostimulation were studied.

Results. Mdivi-1 showed no neuroprotective effect on mature hippocampal neurons following kainic acid administration, but reduced microglial activation in the dentate gyrus without affecting reactive astrogliosis. Mdivi-1 also suppressed maturation and differentiation of granule layer hippocampal neurons in both control animals and the kainate model, but no positive behavioral effects of mdivi-1 exposure were observed.

Conclusion. The data indicate the potential of modulating aberrant neurogenesis through inhibition of mitochondrial division; however, the practical prospects of using mdivi-1 for addressing abnormal processes in the hippocampus are limited by the multiplicity of mdivi-1 effects on different hippocampal cell populations and the complexity of their control.

Введение. Ингибитор деления митохондрий mdivi-1 обладает нейропротекторным потенциалом, а также может модулировать патологическую нейропластичность, что представляет интерес для разработки фармакологических методов терапии мезиальной височной эпилепсии.

Цель работы — обобщить результаты серии экспериментов с mdivi-1 на модели каинат-индуцированного повреждения гиппокампа и оценить перспективы модуляции митохондриальной динамики для подавления нейродегенерации и аберрантной пластичности.

Материалы и методы. Крысам Вистар вводили каиновую кислоту в гиппокамп и mdivi-1 в боковые желудочки мозга. Иммуноморфологически оценивали пролиферацию и дифференцировку (с помощью BrdU), созревание и повреждение нейронов гранулярного слоя гиппокампа (оценивая число NeuN- и DCX-позитивных клеток), глиальную реакцию и изменения митохондриальной динамики (белок, связанный с динамином, и митофузин 2). Изучали способность животных к распознаванию новых объектов и реакцию на фотостимуляцию.

Результаты. Mdivi-1 не оказывал нейропротекторного действия на зрелые нейроны гиппокампа при введении каиновой кислоты, но снижал активацию микроглии в зубчатой извилине, не влияя на реактивную астроглию. Также mdivi-1 подавлял созревание и дифференцировку нейронов гранулярного слоя гиппокампа у контрольных животных и на модели с введением каината, но позитивных поведенческих эффектов при воздействии mdivi-1 не обнаружено.

Заключение. Полученные данные указывают на возможность модуляции аберрантного нейрогенеза путём ингибирования деления митохондрий, однако практические перспективы применения mdivi-1 для коррекции патологических процессов в гиппокампе ограничивают множественность эффектов mdivi-1 в отношении разных клеточных популяций гиппокампа и сложность их контроля.

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