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<article article-type="research-article" dtd-version="1.3" xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" xml:lang="ru"><front><journal-meta><journal-id journal-id-type="publisher-id">vavilov</journal-id><journal-title-group><journal-title xml:lang="ru">Вавиловский журнал генетики и селекции</journal-title><trans-title-group xml:lang="en"><trans-title>Vavilov Journal of Genetics and Breeding</trans-title></trans-title-group></journal-title-group><issn pub-type="epub">2500-3259</issn><publisher><publisher-name>Institute of Cytology and Genetics of Siberian Branch of the RAS</publisher-name></publisher></journal-meta><article-meta><article-id pub-id-type="doi">10.18699/VJGB-22-44</article-id><article-id custom-type="elpub" pub-id-type="custom">vavilov-3386</article-id><article-categories><subj-group subj-group-type="heading"><subject>Research Article</subject></subj-group><subj-group subj-group-type="section-heading" xml:lang="ru"><subject>ГЕНЕТИКА ЖИВОТНЫХ</subject></subj-group><subj-group subj-group-type="section-heading" xml:lang="en"><subject>ANIMAL GENETICS</subject></subj-group></article-categories><title-group><article-title>Плотность нейронов в коре головного мозга и гиппокампе мышей линии Clsnt2-KO – модели расстройств аутистического спектра</article-title><trans-title-group xml:lang="en"><trans-title>Neuronal density in the brain cortex and hippocampus in Clsnt2-KO mouse strain modeling autistic spectrum disorder</trans-title></trans-title-group></title-group><contrib-group><contrib contrib-type="author" corresp="yes"><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Рожкова</surname><given-names>И. Н.</given-names></name><name name-style="western" xml:lang="en"><surname>Rozhkova</surname><given-names>I. N.</given-names></name></name-alternatives><bio xml:lang="ru"><p>Новосибирск</p></bio><bio xml:lang="en"><p>Novosibirsk</p></bio><xref ref-type="aff" rid="aff-1"/></contrib><contrib contrib-type="author" corresp="yes"><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Окотруб</surname><given-names>С. В.</given-names></name><name name-style="western" xml:lang="en"><surname>Okotrub</surname><given-names>S. V.</given-names></name></name-alternatives><bio xml:lang="ru"><p>Новосибирск</p></bio><bio xml:lang="en"><p>Novosibirsk</p></bio><xref ref-type="aff" rid="aff-2"/></contrib><contrib contrib-type="author" corresp="yes"><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Брусенцев</surname><given-names>Е. Ю.</given-names></name><name name-style="western" xml:lang="en"><surname>Brusentsev</surname><given-names>E. Yu.</given-names></name></name-alternatives><bio xml:lang="ru"><p>Новосибирск</p></bio><bio xml:lang="en"><p>Novosibirsk</p></bio><xref ref-type="aff" rid="aff-1"/></contrib><contrib contrib-type="author" corresp="yes"><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Ульданова</surname><given-names>Е. Е.</given-names></name><name name-style="western" xml:lang="en"><surname>Uldanova</surname><given-names>E. E.</given-names></name></name-alternatives><bio xml:lang="ru"><p>Новосибирск</p></bio><bio xml:lang="en"><p>Novosibirsk</p></bio><xref ref-type="aff" rid="aff-1"/></contrib><contrib contrib-type="author" corresp="yes"><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Чуйко</surname><given-names>Э. А.</given-names></name><name name-style="western" xml:lang="en"><surname>Chuyko</surname><given-names>E. А.</given-names></name></name-alternatives><bio xml:lang="ru"><p>Новосибирск</p></bio><bio xml:lang="en"><p>Novosibirsk</p></bio><xref ref-type="aff" rid="aff-2"/></contrib><contrib contrib-type="author" corresp="yes"><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Липина</surname><given-names>Т. В.</given-names></name><name name-style="western" xml:lang="en"><surname>Lipina</surname><given-names>T. V.</given-names></name></name-alternatives><bio xml:lang="ru"><p>Торонто</p></bio><bio xml:lang="en"><p>Toronto</p></bio><xref ref-type="aff" rid="aff-3"/></contrib><contrib contrib-type="author" corresp="yes"><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Амстиславская</surname><given-names>Т. Г.</given-names></name><name name-style="western" xml:lang="en"><surname>Amstislavskaya</surname><given-names>T. G.</given-names></name></name-alternatives><bio xml:lang="ru"><p>Новосибирск</p></bio><bio xml:lang="en"><p>Novosibirsk</p></bio><xref ref-type="aff" rid="aff-4"/></contrib><contrib contrib-type="author" corresp="yes"><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Амстиславский</surname><given-names>С. Я.</given-names></name><name name-style="western" xml:lang="en"><surname>Amstislavsky</surname><given-names>S. Ya.</given-names></name></name-alternatives><bio xml:lang="ru"><p>Новосибирск</p></bio><bio xml:lang="en"><p>Novosibirsk</p></bio><email xlink:type="simple">amstis@yandex.ru</email><xref ref-type="aff" rid="aff-1"/></contrib></contrib-group><aff-alternatives id="aff-1"><aff xml:lang="ru">Федеральный исследовательский центр Институт цитологии и генетики Сибирского отделения Российской академии наук<country>Россия</country></aff><aff xml:lang="en">Institute of Cytology and Genetics of the Siberian Branch of the Russian Academy of Sciences<country>Russian Federation</country></aff></aff-alternatives><aff-alternatives id="aff-2"><aff xml:lang="ru">Федеральный исследовательский центр Институт цитологии и генетики Сибирского отделения Российской академии наук; Новосибирский национальный исследовательский государственный университет<country>Россия</country></aff><aff xml:lang="en">Institute of Cytology and Genetics of the Siberian Branch of the Russian Academy of Sciences; Novosibirsk State University<country>Russian Federation</country></aff></aff-alternatives><aff-alternatives id="aff-3"><aff xml:lang="ru">Университет Торонто<country>Канада</country></aff><aff xml:lang="en">University of Toronto<country>Canada</country></aff></aff-alternatives><aff-alternatives id="aff-4"><aff xml:lang="ru">Научно-исследовательский институт нейронаук и медицины<country>Россия</country></aff><aff xml:lang="en">Scientific Research Institute of Neurosciences and Medicine<country>Russian Federation</country></aff></aff-alternatives><pub-date pub-type="collection"><year>2022</year></pub-date><pub-date pub-type="epub"><day>07</day><month>07</month><year>2022</year></pub-date><volume>26</volume><issue>4</issue><fpage>365</fpage><lpage>370</lpage><permissions><copyright-statement>Copyright &amp;#x00A9; Рожкова И.Н., Окотруб С.В., Брусенцев Е.Ю., Ульданова Е.Е., Чуйко Э.А., Липина Т.В., Амстиславская Т.Г., Амстиславский С.Я., 2022</copyright-statement><copyright-year>2022</copyright-year><copyright-holder xml:lang="ru">Рожкова И.Н., Окотруб С.В., Брусенцев Е.Ю., Ульданова Е.Е., Чуйко Э.А., Липина Т.В., Амстиславская Т.Г., Амстиславский С.Я.</copyright-holder><copyright-holder xml:lang="en">Rozhkova I.N., Okotrub S.V., Brusentsev E.Y., Uldanova E.E., Chuyko E.А., Lipina T.V., Amstislavskaya T.G., Amstislavsky S.Y.</copyright-holder><license license-type="creative-commons-attribution" xlink:href="https://creativecommons.org/licenses/by/4.0/" xlink:type="simple"><license-p>This work is licensed under a Creative Commons Attribution 4.0 License.</license-p></license></permissions><self-uri xlink:href="https://vavilov.elpub.ru/jour/article/view/3386">https://vavilov.elpub.ru/jour/article/view/3386</self-uri><abstract><p>Расстройства аутистического спектра (РАС) – это группа состояний, возникающих в детском возрасте, для которых характерны трудности с социальным взаимодействием и общением, a также нетипичные модели поведения и склонность к стереотипии. Механизмы возникновения этой группы расстройств до сих пор не вполне понятны, и, следовательно, отсутствуют соответствующие методы профилактики. Целью исследования была оценка плотности нейронов в медиальной префронтальной коре и четырех областях гиппокампа, а именно СA1, СA2, СA3 и зубчатой извилины (DG) у мышей линии Clstn2-KO, которая может выступать в качестве генетической модели РАС. Кроме того, охарактеризовали уровень нейрогенеза в области DG гиппокампа. Данная линия получена путем нокаута гена кальсинтенина-2 (Clstn2) на основе мышей линии С57BL/6J; последняя была использована в настоящем исследовании в качестве контроля. Для определения плотности нейронов изготавливали серийные срезы соответствующих областей мозга на криотоме с последующим иммуногистохимическим окрашиванием и конфокальной микроскопией, для чего использовали нейрональный маркер (anti-NeuN) в качестве первичного антитела. Наряду с этим в области DG гиппокампа оценивали нейрогенез, для чего проводили иммуногистохимическое окрашивание с применением антитела против даблкортина (anti-DCX). В обоих случаях в качестве вторичного антитела был Goat anti-rabbit IgG. Плотность нейронов в области гиппокампа СА1 была снижена как у самцов, так и самок мышей Clstn2-KO по сравнению с контролем; у самцов обеих линий плотность нейронов была ниже в этой области по сравнению с самками. Помимо этого, были обнаружены различия между самцами и самками в двух других областях гиппокампа: в области CA2 – у мышей обеих исследованных линий, а в области CA3 лишь у мышей C57BL/6J плотность нейронов была меньше у самцов по сравнению с самками. Различий между исследованными группами в уровне нейрогенеза, а также в плотности нейронов в префронтальной коре и области DG гиппокампа не обнаружено. Полученные результаты показывают, что нокаут по гену Clstn2 приводит к избирательному снижению плотности нейронов в области CA1 гиппокампа, что может представлять собой клеточную мишень для ранней профилактики и возможной терапии РАС.</p></abstract><trans-abstract xml:lang="en"><p>Autistic spectrum disorders (ASD) represent conditions starting in childhood, which are characterized by difficulties with social interaction and communication, as well as non-typical and stereotyping models of behavior. The mechanisms and the origin of these disorders are not yet understood and thus far there is a lack of prophylactic measures for these disorders. The current study aims to estimate neuronal density in the prefrontal cortex and four hippocampal subfields, i. e. СA1, СA2, СA3, and DG in Clstn2-KO mice as a genetic model of ASD. In addition, the level of neurogenesis was measured in the DG area of the hippocampus. This mouse strain was obtained by a knockout of the calsinthenin-2 gene (Clsnt2) in C57BL/6J mice; the latter (wild type) was used as controls. To estimate neuronal density, serial sections were prepared on a cryotome for the above-mentioned brain structures with the subsequent immunohistochemical labeling and confocal microscopy; the neuronal marker (anti-NeuN) was used as the primary antibody. In addition, neurogenesis was estimated in the DG region of the hippocampus; for this purpose, a primary antibody against doublecortin (anti-DCX) was used. In all cases Goat anti-rabbit IgG was used as the secondary antibody. The density of neurons in the CA1 region of the hippocampus was lower in Clstn2-KO mice of both sexes as compared with controls. Moreover, in males of both strains, neuronal density in this region was lower as compared to females. Besides, the differences between males and females were revealed in two other hippocampal regions. In the CA2 region, a lower density of neurons was observed in males of both strains, and in the CA3 region, a lower density of neurons was also observed in males as compared to females but only in C57BL/6J mice. No difference between the studied groups was revealed in neurogenesis, nor was it in neuronal density in the prefrontal cortex or DG hippocampal region. Our new findings indicate that calsyntenin-2 regulates neuronal hippocampal density in subfield-specific manner, suggesting that the CA1 neuronal subpopulation may represent a cellular target for earlylife preventive therapy of ASD.</p></trans-abstract><kwd-group xml:lang="ru"><kwd>мыши</kwd><kwd>кальсинтенин-2</kwd><kwd>мозг</kwd><kwd>плотность нейронов</kwd><kwd>префронтальная кора</kwd><kwd>гиппокамп</kwd><kwd>расстройства аутистического спектра</kwd></kwd-group><kwd-group xml:lang="en"><kwd>mice</kwd><kwd>calsyntenin-2</kwd><kwd>brain</kwd><kwd>neuronal density</kwd><kwd>prefrontal cortex</kwd><kwd>hippocampus</kwd><kwd>autism spectrum disorder</kwd></kwd-group><funding-group xml:lang="en"><funding-statement>This work was funded by the Russian Foundation for Basic Research (grant No. 20-015-00162), as well as budget project No. FWNR-2022-0023 of the Institute of Cytology and Genetics SB RAS (Novosibirsk, Russia). The studies were performed using the equipment of the Centre of Microscopic Analysis of Biological Objects, and the Center for Genetic Resources of Laboratory Animals of the Institute of Cytology and Genetics SB RAS (Novosibirsk, Russia), supported by the Ministry of Education and Science of the Russian Federation (unique project RFMEFI62119X0023).</funding-statement></funding-group></article-meta></front><back><ref-list><title>References</title><ref id="cit1"><label>1</label><citation-alternatives><mixed-citation xml:lang="ru">Bakkaloglu B., O’Roak B.J., Louvi A., Gupta A.R., Abelson J.F., Morgan T.M., Chawarska K., Klin A., Ercan-Sencicek A.G., Stillman A.A., Tanriover G., Abrahams B.S., Duvall J.A., Robbins E.M., Geschwind D.H., Biederer T., Gunel M., Lifton R.P., State M.W. Molecular cytogenetic analysis and resequencing of contactin associated protein-like 2 in autism spectrum disorders. Am. J. Hum. Genet. 2008;82:165-173. 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