fcmedicineФундаментальная и клиническая медицинаFundamental and Clinical Medicine2500-07642542-0941КемГМУ10.23946/2500-0764-2025-10-4-5-21fcmedicine-1101Research ArticleПАТОЛОГИЧЕСКАЯ ФИЗИОЛОГИЯPATHOPHYSIOLOGYОкситоцин-опосредованная модуляция памяти у мышей с экспериментальной моделью болезни Альцгеймера и хронической интоксикации ацетатом цинкаOxytocin-mediated memory modulation in mice with an experimental model of Alzheimer's disease and chronic zinc acetate intoxicationhttps://orcid.org/0000-0002-7101-2717ЦыпуновВ. Е.TsypunovV. E.

Цыпунов Виталий Евгеньевич, младший научный сотрудник лаборатории социальных нейронаук; ассистент кафедры биологической химии с курсом медицинской, фармацевтической и токсикологической химии; аспирант кафедры биофизики

ул. Партизана Железняка, д. 1, г. Красноярск, 660022, Россия

пр. Свободный, д. 79, г. Красноярск, 660041, Россия

. Vitalii E. Tsypunov, junior researcher, Laboratory socialneuroscience, assistant, Department of Biological, Medicinal, Pharmaceutical, and Toxicological Chemistry; Postgraduate student, Department of biophysics

Partizan Zheleznyak Street, 1, Krasnoyarsk, 660022, Russian Federation

Svobodny Avenue, 79, Krasnoyarsk, 660041, Russian Federation

vitaliy.tsypunov.99@mail.ruhttps://orcid.org/0000-0001-7857-0490ПожиленковаЕ. А.PozhilenkovaE. A.

Пожиленкова Елена Анатольевна, кандидат биологических наук, доцент, доцент кафедры БМТ-1 «Биомедицинские технические системы», старший научный сотрудник НОЦ «Мягкая материя и физика флюидов»

ул. 2-я Бауманская, д. 5, стр. 1, г. Москва, 105005, Россия

Elena A. Pozhilenkova, Cand. Sci. (Biology), Associate Professor, Department «Biomedical Engineering Systems», Senior researcher, Scientific and Educational Center «Soft Matterand Fluid Physics»

2-nd Baumanskaya, 5, Moscow, 105005, Russia

ГоринаЯ. В.GorinaYa. V.

Горина Яна Валерьевна, доктор биологических наук, доцент, ведущий научный сотрудник лаборатории социальных нейронаук, профессор кафедры биологической химии с курсом медицинской,фармацевтической и токсикологической химии 

ул. Партизана Железняка, д. 1, г. Красноярск, 660022, Россия

пр. Свободный, д. 79, г. Красноярск, 660041, Россия

Yana V. Gorina – Dr. Sci. (Biology), Associate Professor, leading researcher, Laboratory of social neurosciences, Professor, Department of Biological, Medicinal, Pharmaceutical, and Toxicological Chemistry

Partizan Zheleznyak Street, 1, Krasnoyarsk, 660022, Russian Federation

Svobodny Avenue, 79, Krasnoyarsk, 660041, Russian Federation

https://orcid.org/0000-0002-7884-2721ЛопатинаО. Л.LopatinaO. L.

Лопатина Ольга Леонидовна, доктор биологических наук, доцент, руководитель лаборатории социальных нейронаук, профессор кафедры биологической химии с курсом медицинской, фармацевтической и токсикологической химии; профессор кафедры биофизики

ул. Партизана Железняка, д. 1, г. Красноярск, 660022, Россия

пр. Свободный, д. 79, г. Красноярск, 660041, Россия

Olga L. Lopatina – Dr. Sci. (Biology), Associate Professor, Head, Laboratory of social neurosciences, Professor, Department of Biological, Medicinal, Pharmaceutical, and Toxicological Chemistry; Professor, Department of biophysics

Partizan Zheleznyak Street, 1, Krasnoyarsk, 660022, Russian Federation

Svobodny Avenue, 79, Krasnoyarsk, 660041, Russian Federation

Красноярский государственный медицинский университет; Сибирский федеральный университетРоссияProfessor V.F. Voyno-Yasenetsky Krasnoyarsk State Medical University; Siberian Federal UniversityRussian FederationМосковский государственный технический университет имени Н.Э. БауманаРоссияBauman Moscow State Technical UniversityRussian Federation202524122025104521Copyright © Цыпунов В.Е., Пожиленкова Е.А., Горина Я.В., Лопатина О.Л., 20252025Цыпунов В.Е., Пожиленкова Е.А., Горина Я.В., Лопатина О.Л.Tsypunov V.E., Pozhilenkova E.A., Gorina Y.V., Lopatina O.L.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://fcm.kemsmu.ru/jour/article/view/1101

Цель. Выявить изменения реализации когнитивных функций и уровня эндогенного окситоцина в ряде регионов головного мозга и биологических жидкостях у мышей с экспериментальной моделью болезни Альцгеймера, хронической интоксикации ацетатом цинка и их совместным воздействием. Материалы и методы. Мыши линии CD-1 (n = 32). Моделирование хронической интоксикации ацетатом цинка – Zn(CH3CO2)2 (концентрация Zn2+ 5 мг/л) в качестве питься в течение 3 мес., контрольная группа – чистая вода. Моделирование болезни Альцгеймера – интрагиппокампальная инъекция β-амилоида, контрольная группа – введение фосфатно-солевого буфера. Оценка ассоциативной памяти – тестирование на условно-рефлекторное замирание. Уровень окситоцина в регионах головного мозга и биологических жидкостях – метод иммуноферментного анализа. Результаты. Хроническая интоксикация ацетатом цинка и её сочетанное влияние с β-амилоидом вызвали повышение уровня окситоцина в гиппокампе, энторинальной коре, гипоталамо-гипофизарной области и в спинномозговой жидкости. Воздействие β-амилоида не оказало влияния на уровень окситоцина, либо вызвало его снижение (миндалевидное тело, плазма крови). Формирование условного рефлекса и контекстуальной памяти ухудшилось у мышей всех опытных групп. Ассоциативная память о страхе у мышей с моделью болезни Альцгеймера, сочетанной с хронической интоксикацией ацетатом цинка, не отличалась от контроля. Воздействие только β-амилоида способствовало ухудшению ассоциативной памяти о страхе. Уровень окситоцина в миндалевидном теле согласуется с изменением способности мышей к формированию памяти о страхе. Заключение. Хроническая интоксикация ацетатом цинка и его сочетание с β-амилоидом повышают уровень окситоцина практически во всех исследуемых регионах мозга и в спинномозговой жидкости, вероятно, как компенсаторный ответ на нейротоксичность Zn2+. Острое воздействие β-амилоида не вызывало существенных изменений. Таким образом, хроническое воздействие ацетата цинка – основной фактор повышения уровня окситоцина в мозге и биожидкостях. Повышение уровня окситоцина может способствовать восстановлению когнитивных функций.

Aim. To identify changes in cognitive function performance and endogenous oxytocin levels in various brain regions and biological fluids in mice with an experimental model of Alzheimer’s disease, chronic zinc acetate intoxication, and their combined effects. Materials and methods. CD-1 mice (n = 32). Chronic zinc acetate intoxication was modeled by administering Zn(CH3CO2)2 (Zn2+ concentration: 5 mg/L) as drinking water for 3 months; the control group received pure water. Alzheimer’s disease was modeled via intrahippocampal β-amyloid injection; the control group received phosphate-buffered saline. Associative memory was assessed using conditioned freezing testing. Oxytocin levels in brain regions and biological fluids were measured via ELISA. Results. Chronic zinc acetate intoxication and its combined effect with β-amyloid led to increased oxytocin levels in the hippocampus, entorhinal cortex, hypothalamic-pituitary region, and cerebrospinal fluid. β-Amyloid exposure either had no effect on oxytocin levels or caused a decrease (amygdala, blood plasma). Conditioned reflex formation and contextual memory were impaired in all experimental groups. Fear-associated memory in mice with the Alzheimer’s model combined with chronic zinc acetate intoxication did not differ from controls. Exposure to β-amyloid alone worsened fear-associated memory. Oxytocin levels in the amygdala correlated with changes in the mice’s ability to form fear memory. Conclusion. Chronic zinc acetate intoxication and its combination with β-amyloid increase oxytocin levels in nearly all examined brain regions and cerebrospinal fluid, likely as a compensatory response to Zn2+ neurotoxicity. Acute β-amyloid exposure did not cause significant changes. Thus, chronic zinc acetate exposure is the primary factor elevating oxytocin levels in the brain and biofluids. Increased oxytocin levels may contribute to the restoration of cognitive functions.

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