phkineticaФармакокинетика и ФармакодинамикаPharmacokinetics and Pharmacodynamics2587-78362686-8830ООО «Издательство ОКИ»10.37489/2587-7836-2025-4-17-25phkinetica-481Research ArticleМЕХАНИЗМ ДЕЙСТВИЯMECHANISM OF ACTIONВлияние дипептидного миметика BDNF (соединение ГСБ-106) на формирование рефлексов и уровни моноаминов у крыс Вистар с экспериментальным расстройством аутистического спектраEffect of the dipeptide BDNF mimetic (compound GSB-106) on reflex development and monoamine levels in Wistar rats with an experimental autism spectrum disorderhttps://orcid.org/0009-0007-7876-5977СавинковаЕ. В.SavinkovaE. V.

Савинкова Елена Владимировна — м. н. с. лаборатории фармакологии психических заболеваний отдела нейропсихофармакологии

Москва

Elena V. Savinkova — Junior Researcher at the Laboratory of Pharmacology of Mental Diseases of the Department of Neuropsychopharmacology

Moscow

savinkova_ev@academpharm.ruhttps://orcid.org/0000-0003-4487-0991КапицаИ. Г.KapitsaI. G.

Капица Инга Геннадиевна — к. б. н., в. н. с. лаборатории фармакологии психических заболеваний отдела нейропсихофармакологии

Москва

Inga G. Kapitsa — PhD, Cand. Sci. (Biology), Leading Researcher of the Laboratory of Pharmacology of Mental Disorders, Department of Neuropsychopharmacology

Moscow

kapica_ig@academpharm.ruhttps://orcid.org/0000-0002-0321-5125КудринВ. С.KudrinV. S.

Кудрин Владимир Сергеевич — к. м. н., заведующий лабораторией нейрохимической фармакологии

Москва

Vladimir S. Kudrin — PhD, Cand. Sci. (Med.), Head of the Laboratory of Neurochemical Pharmacology

Moscow

НаркевичВ. Б.NarkevichV. B.

Наркевич Виктор Борисович — к. м. н., с. н. с. группы нейрохимических исследований лаборатории нейрофизиологии и нейрохимии

Москва

Victor B. Narkevich — PhD, Cand. Sci. (Med.), Senior Research Scientist of Neurochemical Research Group, Laboratory of Neurophysiology and Neurochemistry

Moscow

https://orcid.org/0000-0001-7065-469XВоронинаВ. Б.VoroninaT. A.

Воронина Татьяна Александровна — д. м. н., профессор, руководитель лаборатории фармакологии психических заболеваний и отдела нейропсихофармакологии

Москва

Tatiana A. Voronina — PhD, Dr. Sci. (Med.), Professor, Head the Laboratory of Pharmacology of Mental Disorders and Neuropsychopharmacology Department

Moscow

voronina_ta@academpharm.ruФГБНУ «ФИЦ оригинальных и перспективных биомедицинских и фармацевтических технологий»РоссияFederal research center for innovator and emerging biomedical and pharmaceutical technologiesRussian Federation202530122025041725Copyright © Савинкова Е.В., Капица И.Г., Кудрин В.С., Наркевич В.Б., Воронина В.Б., 20262026Савинкова Е.В., Капица И.Г., Кудрин В.С., Наркевич В.Б., Воронина В.Б.Savinkova E.V., Kapitsa I.G., Kudrin V.S., Narkevich V.B., Voronina T.A.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://www.pharmacokinetica.ru/jour/article/view/481

Расстройство аутистического спектра (РАС) представляет собой нарушение нейроразвития, сопровождающееся изменениями в серотонинергической, дофаминергической и норадренергической системах, а также задержкой раннего психомоторного и сенсомоторного развития. Одним из подходов к коррекции данных нарушений может быть использование миметиков BDNF, регулирующих синаптическую пластичность и нейрогенез. Целью исследования было изучение влияния низкомолекулярного дипептидного миметика BDNF гексаметилендиамид бис(N-моносукцинил-L-серил-L-лизина (ГСБ-106) на рефлекторное развитие и содержание моноаминов в структурах мозга крыс линии Вистар с экспериментальным РАС. Моделирование РАС проводили посредством введения вальпроата натрия (600 мг/кг) на 12,5 день гестации крыс. Полученному потомству вводили ГСБ-106 перорально в дозе 0,1 мг/кг с 7-го по 21-й день постнатального развития. Скорость формирования сенсомоторных рефлексов оценивали в тестах «Переворачивание на плоскости» и «Отрицательный геотаксис», уровни моноаминов и их метаболитов определяли методом ВЭЖХ с электрохимической детекцией. Соединение ГСБ-106 улучшало показатели отрицательного геотаксиса у самцов и самок крыс с РАС (в 1,8–2,3 раза), нормализовало содержание NA и DOPAC во фронтальной коре у самок, а также снижало уровни DA и 5-HT в структурах мозга у самцов. Таким образом, ГСБ-106 оказывает нормализующее действие на нарушенное раннее поведенческое развитие и моноаминергические системы у крыс с моделью РАС, что позволяет рассматривать его как перспективное средство для дальнейших исследований.

Autism spectrum disorder (ASD) is a neurodevelopmental condition accompanied by alterations in serotonergic, dopaminergic, and noradrenergic systems, as well as delays in early psychomotor and sensorimotor development. One possible approach to correcting these disturbances is the use of BDNF mimetics that regulate synaptic plasticity and neurogenesis. The aim of this study was to investigate the effect of the low-molecular-weight dipeptide BDNF mimetic hexamethylenediamide bis(N-monosuccinyl-L-seryl-L-lysine) (GSB-106) on reflex development and monoamine content in the brain structures of Wistar rats with experimental ASD. The ASD model was induced by administration of sodium valproate (600 mg/kg) on gestation day 12.5. Offspring received GSB-106 orally at a dose of 0.1 mg/kg from postnatal day 7 to 21. The rate of sensorimotor reflex development was evaluated using the “Surface righting” and “Negative geotaxis” tests. Monoamines and their metabolites were quantified by high-performance liquid chromatography with electrochemical detection. GSB-106 improved negative geotaxis performance in both male and female rats with ASD (by 1.8–2.3 times), normalized NA and DOPAC levels in the frontal cortex of females, and reduced DA and 5-HT levels in male brain structures. Thus, GSB-106 exerts a normalizing effect on impaired early behavioral development and monoaminergic systems in rats with an ASD model, suggesting its potential as a promising compound for further investigation.

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