Mitochondrial fission as a target for supressing aberrant neuroplasticity and degeneration in the hippocampus

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Abstract

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.

About the authors

Dmitry N. Voronkov

Russian Center of Neurology and Neurosciences

Author for correspondence.
Email: voronkov@neurology.ru
ORCID iD: 0000-0001-5222-5322

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

Russian Federation, Moscow

Evgenia N. Fedorova

Russian Center of Neurology and Neurosciences; Pirogov Russian National Research Medical University

Email: ewgenia.feodorowa2011@yandex.ru
ORCID iD: 0000-0002-2128-9056

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

Russian Federation, Moscow; Moscow

Anastasia K. Pavlova

Russian Center of Neurology and Neurosciences

Email: pav_nastasya@mail.ru
ORCID iD: 0009-0006-5653-5524

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

Russian Federation, Moscow

Maria S. Ryabova

Russian Center of Neurology and Neurosciences

Email: voronkov@neurology.ru
ORCID iD: 0009-0003-5596-7630

research assistant, Laboratory of neuromorphology

Russian Federation, Moscow

Anna V. Egorova

Russian Center of Neurology and Neurosciences; Pirogov Russian National Research Medical University

Email: av_egorova@bk.ru
ORCID iD: 0000-0001-7112-2556

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

Russian Federation, Moscow; Moscow

Alla V. Stavrovskaya

Russian Center of Neurology and Neurosciences

Email: alla_stav@mail.ru
ORCID iD: 0000-0002-8689-0934

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

Russian Federation, Moscow

Ivan A. Potapov

Russian Center of Neurology and Neurosciences

Email: potapov.i.a@neurology.ru
ORCID iD: 0000-0002-7471-3738

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

Russian Federation, Moscow

Vladimir S. Sukhorukov

Russian Center of Neurology and Neurosciences; Pirogov Russian National Research Medical University

Email: voronkov@neurology.ru
ORCID iD: 0000-0002-0552-6939

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

Russian Federation, Moscow; Moscow

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Copyright (c) 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.

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