fcmedicineФундаментальная и клиническая медицинаFundamental and Clinical Medicine2500-07642542-0941КемГМУ10.23946/2500-0764-2025-10-3-87-99fcmedicine-1067Research ArticleПАТОЛОГИЧЕСКАЯ ФИЗИОЛОГИЯ, ИММУНОЛОГИЯPATHOPHISIOLOGY, IMMUNOOGYНарушение социального поведения при болезни Альцгеймера в условиях социальной изоляцииSocial behavior disorders in Alzheimer's disease in social isolationhttps://orcid.org/0009-0008-3803-1490ПероваЕ. К.PerovaE. K.

Перова Екатерина Константиновна, младший научный сотрудник лаборатории социальных нейронаук; ассистент кафедры биологической химии с курсом медицинской, фармацевтической и токсикологической химии 

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

Dr. Ekaterina K. Perova, MD, Junior Researcher, Laboratory of Social Neuroscience; Assistant Professor, Department of Biological, Medicinal, Pharmaceutical, and Toxicological Chemistry

Partizana Zheleznyaka Street, 1, Krasnoyarsk, 660022

https://orcid.org/0009-0009-8457-4581АвлиякулыеваА. М.AvliyakulyevaA. M.

Авлиякулыева Айлар Мередовна, младший научный сотрудник лаборатории социальных нейронаук; ассистент кафедры биологической химии с курсом медицинской, фармацевтической и токсикологической химии 

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

Dr. Aylar M. Avliyakulyeva, MD, Junior Researcher, Laboratory of Social Neuroscience; Assistant Professor, Department of Biological, Medicinal, Pharmaceutical, and Toxicological Chemistry

Partizana Zheleznyaka Street, 1, Krasnoyarsk, 660022

https://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 

Dr. Vitaliy E. Tsypunov, MD, Junior Researcher, Laboratory of Social Neuroscience; Assistant Professor, Department of Biological, Medicinal, Pharmaceutical, and Toxicological Chemistry; Postgraduate student Department of Biophysics

Partizana Zheleznyaka Street, 1, Krasnoyarsk, 660022

Svobodny Avenue, 79, Krasnoyarsk, 660041

https://orcid.org/0000-0002-3341-1557ГоринаЯ. В.GorinaT. 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;  профессор кафедры биофизики 

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

Dr. Yana V. Gorina, Dr. Sci. (Biology), Leading Researcher, Laboratory of Social Neuroscience; Professor, Department of Biological, Medicinal, Pharmaceutical, and Toxicological Chemistry; Professor, Department of Biophysics

Partizana Zheleznyaka Street, 1, Krasnoyarsk, 660022

Svobodny Avenue, 79, Krasnoyarsk, 660041

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 

Dr. Olga L. Lopatina, Dr. Sci. (Biology), Head of Laboratory of social Neuroscience; Professor, Department of Biological, Medicinal, Pharmaceutical, and Toxicological Chemistry; Professor, Department of Biophysics

Partizana Zheleznyaka Street, 1, Krasnoyarsk, 660022

Svobodny Avenue, 79, Krasnoyarsk, 660041

Красноярский государственный медицинский университетРоссияProfessor V. F. Voyno-Yasenetsky Krasnoyarsk State Medical UniversityRussian FederationКрасноярский государственный медицинский университет; Сибирский федеральный университетРоссияProfessor V. F. Voyno-Yasenetsky Krasnoyarsk State Medical University; Siberian Federal UniversityRussian Federation2025290920251038799Copyright © Перова Е.К., Авлиякулыева А.М., Цыпунов В.Е., Горина Я.В., Лопатина О.Л., 20252025Перова Е.К., Авлиякулыева А.М., Цыпунов В.Е., Горина Я.В., Лопатина О.Л.Perova E.K., Avliyakulyeva A.M., Tsypunov V.E., Gorina T.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/1067

Цель. Изучить влияние социальной изоляции на социальное поведение и уровень маркеров психоэмоционального состояния (окситоцин и вазопрессин) у мышей с инъекционной моделью болезни Альцгеймера. Материалы и методы. Объект исследования – мыши линии CD1, самцы возрастом 3 – 4 месяца. Моделирование нейродегенерации альцгеймеровского типа проводили путем интрагиппокампального введения раствора Аβ 1-42 (экспериментальная болезнь Альцгеймера). Мышам контрольной группы (ложно-оперированные животные (Sham)) вводили фосфатно-солевой буфер. Часть мышей экспериментальной и контрольной групп подвергалась социальной изоляции в течение 21 суток (AD + isol и Sham + isol соответственно). Для изучения социального поведения проводили батарею нейроповеденческих тестов (социальный пятипопытоный тест, трехкамерный социальный тест и тест Открытое поле расширенный). Определение уровня окситоцина и вазопрессина в определенных областях головного мозга проводили методом иммуноферментного анализа. Результаты. Согласно результатам нейроповеденческих тестов у мышей с экспериментальной моделью болезни Альцгеймера (AD) нарушена социализация и способность к запоминанию и распознаванию новых особей. Под действием социальной изоляции наблюдаются увеличение двигательной активности, нарушение исследовательского интереса к неодушевленному объекту, изменения в характере социальных взаимодействий и их частоте. Подобная трансформация эмоциональных и социальных паттернов поведения связана с изменением регуляции окситоцин – и вазопрессинергической системы в миндалевидном теле. Выявлено снижение уровня окситоцина в обонятельных луковицах у мышей с моделью БА (AD) по сравнению с контролем (Sham). У животных с экспериментальной моделью болезни Альцгеймера в условиях изоляции (AD+isol) обнаружено повышение уровня вазопрессина и тенденция к снижению уровня окситоцина в миндалевидном теле, по сравнению с контрольной группой (Sham+isol). Заключение. Полученные результаты в очередной раз показывают необходимость недопущения изоляции среди пациентов с диагностированной БА. Связь окситоцин- и вазопрессинергической систем с прогрессированием поведенческих нарушений показывает необходимость проведения дальнейших исследований по изучению окситоцина и вазопрессина в качестве терапевтических молекул при болезни Альцгеймера.

Aim. To investigate the effect of social isolation on social behavior and levels of psychoemotional markers (oxytocin and vasopressin) in mice with an injection-induced model of Alzheimer’s disease (AD). Materials and Methods. The study was conducted on CD1 male mice aged 3–4 months, which received intrahippocampal injection of either β-amyloid (in order to induce AD) or control phosphate-buffered saline (sham-operated mice). Subsets of experimental and control animals were subjected to social isolation for 21 days. To assess social behavior, a battery of neurobehavioral tests was applied, including the five-trial social memory/recognition test, the three-chamber social interaction test, and the extended open field test. Levels of oxytocin and vasopressin in specific brain regions were measured using enzyme-linked immunosorbent assay. Results. Neurobehavioral testing showed impaired socialization and reduced ability to memorize and recognize novel conspecifics in AD mice. Social isolation induced increased locomotor activity, diminished exploratory interest toward inanimate objects, and altered the character and frequency of social interactions. These transformations of emotional and social behavior were associated with dysregulation of the oxytocinergic and vasopressinergic systems in the amygdala. A reduction in oxytocin levels was observed in the olfactory bulbs of AD mice compared with controls. Isolated AD mice had elevated vasopressin levels and a trend toward decreased oxytocin levels in the amygdala as compared with the isolated control mice. Conclusion. Our results highlight the critical need to prevent social isolation in patients diagnosed with AD. The link between oxytocinergic and vasopressinergic systems and the progression of behavioral disorders underscores the importance of further studies on oxytocin and vasopressin as potential therapeutic molecules in Alzheimer’s disease.

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