scbmtБИОМЕДИЦИНАJournal Biomed2074-59822713-0428Scientific center of biomedical technologies of Federal Medical and Biological Agencyscbmt-72Research ArticleРЕЛЕВАНТНОЕ И АЛЬТЕРНАТИВНОЕ БИОМОДЕЛИРОВАНИЕRELEVANT AND ALTERNATIVE BIOMODELLINGПоведенческий фенотипический анализ животных с генетической моделью болезни АльцгеймераBehavioral phenotypic analysis of animals with a genetic model of Alzheimer's diseaseГоринаЯ. В.GorinaYa. V.yana_20@bk.ruКомлеваЮ. К.KomlevaYu. K.noemail@neicon.ruЛопатинаО. Л.LopatinaO. L.noemail@neicon.ruЧерныхА. И.ChernykhA. I.noemail@neicon.ruСалминаА. Б.SalminaA. B.noemail@neicon.ruНИИ молекулярной медицины и патобиохимии, Федеральное государственное бюджетное образовательное учреждение высшего образования "Красноярский государственный медицинский университет имени профессора В.Ф.Войно-Ясенецкого" Министерства здравоохранения Российской ФедерацииRussian FederationКрасноярская межрайонная клиническая больница №20 им. И.С.БерзонаRussian Federation201726022019034759Copyright © Горина Я.В., Комлева Ю.К., Лопатина О.Л., Черных А.И., Салмина А.Б., 20192019Горина Я.В., Комлева Ю.К., Лопатина О.Л., Черных А.И., Салмина А.Б.Gorina Y.V., Komleva Y.K., Lopatina O.L., Chernykh A.I., Salmina A.B.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://journal.scbmt.ru/jour/article/view/72

Основным симптомом болезни Альцгеймера является быстро прогрессирующее слабоумие, коррелирующее с образованием амилоидных бляшек и нейрофибриллярных белков в ткани головного мозга, что приводит к гибели нейронов, синоптической и когнитивной дисфункции. Цель исследования - изучение развития социальных и когнитивных нарушений в процессе онтогенеза у животных с генетической моделью болезни Альцгеймера. Объект исследования - Генетическая модель болезни Альцгеймера - мыши линии B6SLJ -Tg(APPSwFlLon,PSEN1*M146L*L286V)6799Vas, самцы в возрасте 4 месяцев (n=10). Контрольная группа - мыши линии C57BL/6 x SJL, самцы в возрасте 4 месяцев (n=10). Нейроповеденческое тестирование включало в себя следующие протоколы тестов: тест «открытое поле», приподнятый крестообразный лабиринт, тест «черно-белая камера», «трехкамерный социальный тест», социальный пятипопыточный тест, тест «Fear conditioning». В результате проведения нейроповеденческого тестирования у животных линии Tg 6799 по мере развития болезни Альцгеймера выявлены следующие особенности поведения: повышение уровня тревожности и заторможенности, нарушение социальных контактов и взаимодействий, а также пространственного, социального и ассоциативного обучения и запоминания. В совокупности это указывает на расстройство эмоционального поведения, а также долговременной, социальной, пространственной и эмоциональной памяти.

The main symptom of Alzheimer's disease is rapidly progressive dementia, which correlates with the formation of amyloid plaques and neurofibrillary proteins in tissue of the brain. This leads to the death of neurons, synoptic and cognitive dysfunction. The aim of the study was to study the development of social and cognitive impairments in the process of ontogenesis in animals with a genetic model of Alzheimer's disease. The object of the study is a genetic model of Alzheimer's disease is the B6SLJ-Tg line mice (APPSwFlLon, PSEN1 * M146L * L286V) 6799Vas, males aged 4 months. Control group - C57BL / 6 x SJL mice, males aged 4 months. Neurobehavioral testing included the following protocols: test «open field», elevated plus maze, light/dark transition test, a three-chamber social test, social recognition memory test in rodents, test «Fear conditioning». We identified features of behavioral in animals Tg 6799 line with the development of Alzheimer's disease. This increase the level of anxiety and lethargy, impaired social contacts and interactions, as well as spatial, social and associative learning and memory. Together, this indicates a disorder of emotional behavior, as well as long-term, social, spatial and emotional memory.

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P. 729-736. doi:10.1001/archneur.60.5.729.Jacobs S.A., Huang F., Tsien J.Z., Wei W. Social Recognition Memory Test in Rodents // Neuroscience. 2016. No. 6(9). doi: https://doi.org/10.21769/bioprotoc.1804.Jacobs S.A., Huang F., Tsien J.Z., Wei W. Social Recognition Memory Test in Rodents // Neuroscience. 2016. No. 6(9). doi: https://doi.org/10.21769/bioprotoc.1804.Leal S.L., Landau S.M., Bell R.K., Jagust W.J. Hippocampal activation is associated with longitudinal amyloid accumulation and cognitive decline // Elife. 2017. 6. pii: e22978. doi: 10.7554/eLife.22978. [Epub ahead of print].Leal S.L., Landau S.M., Bell R.K., Jagust W.J. Hippocampal activation is associated with longitudinal amyloid accumulation and cognitive decline // Elife. 2017. 6. pii: e22978. doi: 10.7554/eLife.22978. [Epub ahead of print].Leo L.M., Pamplona F. A. Elevated Plus Maze Test to Assess Anxiety-like Behavior in the Mouse // Neuroscience. 2014. No 4(16). doi: https://doi.org/10.21769/bioprotoc.1211.Leo L.M., Pamplona F. A. Elevated Plus Maze Test to Assess Anxiety-like Behavior in the Mouse // Neuroscience. 2014. No 4(16). doi: https://doi.org/10.21769/bioprotoc.1211.Lugo J.N., Smith G.D., Holley A.J. Trace fear conditioning in mice // J. Vis. Exp. 2014. No. 85. doi: 10.3791/51180.Lugo J.N., Smith G.D., Holley A.J. Trace fear conditioning in mice // J. Vis. Exp. 2014. No. 85. doi: 10.3791/51180.Mak E., Gabel S., Su L., Williams G.B., Arnold R., Passamonti L., Vazquez Rodríguez P., Surendranathan A., Bevan-Jones W.R., Rowe J.B., O'Brien J.T. Multi-modal MRI investigation of volumetric and microstructural changes in the hippocampus and its subfields in mild cognitive impairment, Alzheimer's disease, and dementia with Lewy bodies // Int. Psychogeriatr. 2017. P. 1-11. doi: 10.1017/s1041610216002143. [Epub ahead of print].Mak E., Gabel S., Su L., Williams G.B., Arnold R., Passamonti L., Vazquez Rodríguez P., Surendranathan A., Bevan-Jones W.R., Rowe J.B., O'Brien J.T. Multi-modal MRI investigation of volumetric and microstructural changes in the hippocampus and its subfields in mild cognitive impairment, Alzheimer's disease, and dementia with Lewy bodies // Int. Psychogeriatr. 2017. P. 1-11. doi: 10.1017/s1041610216002143. [Epub ahead of print].Martin L, Iceberg E. Quantifying Social Motivation in Mice Using Operant Conditioning // J. Vis. Exp. 2015. No. 102. e53009. doi: 10.3791/53009.Martin L, Iceberg E. Quantifying Social Motivation in Mice Using Operant Conditioning // J. Vis. Exp. 2015. No. 102. e53009. doi: 10.3791/53009.Morland R.H., Novejarque A., Spicer C., Pheby T., Rice A.S. Enhanced c-Fosexpression in the central amygdala correlates with increased thigmotaxis inrats with peripheral nerve injury // Eur. J. Pain (Lond. Engl.). 2016. No. 20(7). P.1140-1154. doi: 10.1002/ejp.839.Morland R.H., Novejarque A., Spicer C., Pheby T., Rice A.S. Enhanced c-Fosexpression in the central amygdala correlates with increased thigmotaxis inrats with peripheral nerve injury // Eur. J. Pain (Lond. Engl.). 2016. No. 20(7). P.1140-1154. doi: 10.1002/ejp.839.Nesteruk M., Nesteruk T., Styczyńska M., Mandecka M., Barczak A., Barcikowska M. Combined use of biochemical and volumetric biomarkers to assess the risk of conversion of mild cognitive impairment to Alzheimer's disease // Folia Neuropathol. 2016. No. 54(4). P. 369-374. doi: 10.5114/fn.2016.64815.Nesteruk M., Nesteruk T., Styczyńska M., Mandecka M., Barczak A., Barcikowska M. Combined use of biochemical and volumetric biomarkers to assess the risk of conversion of mild cognitive impairment to Alzheimer's disease // Folia Neuropathol. 2016. No. 54(4). P. 369-374. doi: 10.5114/fn.2016.64815.Prieto G.A., Trieu B.H., Dang C.T., Bilousova T., Gylys K.H., Berchtold N.C., Lynch G., Cotman C.W. Pharmacological Rescue of Long-Term Potentiation in Alzheimer Diseased Synapses // J. Neurosci. 2017. No. 37(5). P. 1197-1212. doi: 10.1523/jneurosci.2774-16.2016.Prieto G.A., Trieu B.H., Dang C.T., Bilousova T., Gylys K.H., Berchtold N.C., Lynch G., Cotman C.W. Pharmacological Rescue of Long-Term Potentiation in Alzheimer Diseased Synapses // J. Neurosci. 2017. No. 37(5). P. 1197-1212. doi: 10.1523/jneurosci.2774-16.2016.Robinson M., Lee B.Y., Hane F.T. Recent Progress in Alzheimer's Disease Research, Part 2: Genetics and Epidemiology // J. Alzheimers Dis. 2017. doi: 10.3233/jad-161149. [Epub ahead of print].Robinson M., Lee B.Y., Hane F.T. Recent Progress in Alzheimer's Disease Research, Part 2: Genetics and Epidemiology // J. Alzheimers Dis. 2017. doi: 10.3233/jad-161149. [Epub ahead of print].Seibenhener M.L., Wooten M.C. Use of the Open Field Maze to Measure Locomotor and Anxiety-like Behavior in Mice // J. Vis. Exp. 2015. No. 96. e52434. doi:10.3791/52434.Seibenhener M.L., Wooten M.C. Use of the Open Field Maze to Measure Locomotor and Anxiety-like Behavior in Mice // J. Vis. Exp. 2015. No. 96. e52434. doi:10.3791/52434.Takao K., Miyakawa T. Light/dark Transition Test for Mice // J. Vis. Exp. 2006. No. 1. e104. doi:10.3791/104.Takao K., Miyakawa T. Light/dark Transition Test for Mice // J. Vis. Exp. 2006. No. 1. e104. doi:10.3791/104.Thangavel R., Van Hoesen G.W., Zaheer A. Posterior parahippocampal gyrus pathology in Alzheimer’s disease // Neuroscience. 2008. No. 154(2). P. 667-676. doi:10.1016/j.neuroscience.2008.03.077.Thangavel R., Van Hoesen G.W., Zaheer A. Posterior parahippocampal gyrus pathology in Alzheimer’s disease // Neuroscience. 2008. No. 154(2). P. 667-676. doi:10.1016/j.neuroscience.2008.03.077.

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