vavilovВавиловский журнал генетики и селекцииVavilov Journal of Genetics and Breeding2500-3259Institute of Cytology and Genetics of Siberian Branch of the RAS10.18699/VJGB-23-14vavilov-3683Research ArticleГЕНЕТИКА ЖИВОТНЫХANIMAL GENETICSИзменения в социальном предпочтении места и плотность дофаминергических нейронов в вентральном тегментуме у Clsnt2-KO мышейAlterations in the social-conditioned place preference and density of dopaminergic neurons in the ventral tegmental area in Clsnt2-KO miceРожковаИ. Н.RozhkovaI. N.

Novosibirsk

ОкотрубС. В.OkotrubS. V.

Novosibirsk

БрусенцевЕ. Ю.BrusentsevE. Yu.

Novosibirsk

УльдановаЕ. Е.UldanovaK. E.

Novosibirsk

ЧуйкоЭ. А.ChuykoE. A.

Novosibirsk

НапримеровВ. А.NaprimerovV. A.

Новосибирск

Novosibirsk

ЛипинаТ. В.LipinaT. V.

Торонто

Toronto

АмстиславскаяТ. Г.AmstislavskayaT. G.

Новосибирск

Novosibirsk

АмстиславскийС. Я.AmstislavskyS. Ya.

Новосибирск

Novosibirsk

amstis@yandex.ruФедеральный исследовательский центр Институт цитологии и генетики, Сибирское отделение Российской академии наукРоссияInstitute of Cytology and Genetics, Siberian Branch of the Russian Academy of SciencesRussian FederationInstitute of Cytology and Genetics, Siberian Branch of the Russian Academy of SciencesRussian FederationФедеральный исследовательский центр Институт цитологии и генетики, Сибирское отделение Российской академии наук; Новосибирский государственный аграрный университетРоссияInstitute of Cytology and Genetics, Siberian Branch of the Russian Academy of Sciences; Novosibirsk State Agricultural UniversityRussian FederationУниверситет ТоронтоКанадаUniversity of TorontoCanadaНаучно-исследовательский институт нейронаук и медицины, Сибирское отделение Российской академии наукРоссияScientific Research Institute of Neurosciences and MedicineRussian Federation202306042023272177184Copyright © Рожкова И.Н., Окотруб С.В., Брусенцев Е.Ю., Ульданова Е.Е., Чуйко Э.А., Напримеров В.А., Липина Т.В., Амстиславская Т.Г., Амстиславский С.Я., 20232023Рожкова И.Н., Окотруб С.В., Брусенцев Е.Ю., Ульданова Е.Е., Чуйко Э.А., Напримеров В.А., Липина Т.В., Амстиславская Т.Г., Амстиславский С.Я.Rozhkova I.N., Okotrub S.V., Brusentsev E.Y., Uldanova K.E., Chuyko E.A., Naprimerov V.A., Lipina T.V., Amstislavskaya T.G., Amstislavsky S.Y.This work is licensed under a Creative Commons Attribution 4.0 License.https://vavilov.elpub.ru/jour/article/view/3683

В мире наблюдается рост случаев расстройств аутистического спектра (РАС). Исследование механизмов и причин возникновения РАС, а также поиск мишеней для терапии этих расстройств являются актуальной задачей. Многие исследователи сходятся во мнении, что возникновение аутизма связано с нарушением развития нервной системы. Линия мышей Clstn2-KO, нокаутов по гену кальсинтенин-2, полученная на основе C57BL/6J, моделирует симптомы РАС. Данное исследование было направлено на изучение у самцов Clstn2-KO социального предпочтения места и плотности дофаминергических нейронов в вентральном тегментуме, который представляет собой часть системы вознаграждения головного мозга, в сравнении с контрольной линией мышей C57BL/6J дикого типа. Тест «социально обусловленное предпочтение места» отражает социальное вознаграждение. Результаты этого теста показали, что у самцов Clstn2-KO наблюдаются отклонения от контрольных мышей в социальном вознаграждении, так как они проводили одинаковое время в обоих отсеках установки, ассоциированных либо с изоляцией, либо с социализацией со знакомым партнером. При этом животные из группы Clstn2-KO заходили в обе части камеры значительно чаще, но проводили меньше времени в социально-ассоциированном отсеке по сравнению с контрольной группой. Самцы контрольной линии C57BL/6J, напротив, проводили больше времени в отсеке, ассоциированном с социализацией, где было взаимодействие с сородичем, и меньше в отсеке, в котором ранее особь находилась в одиночестве. В вентральном тегментуме, отвечающем за процессы, связанные с вознаграждением, у мышей Clstn2-KO было обнаружено повышенное число дофаминергических нейронов и, возможно, ГАМК-ергических нейронов, меченных антителами против дофаминового рецептора второго типа и тирозингидроксилазы. На основании полученных результатов можно заключить, что у мышей Clstn2-KO имеет место изменение значимости социального вознаграждения, а также обнаружено повышенное число нейронов, экспрессирующих дофаминовые рецепторы второго типа и тирозингидроксилазу, в одной из важных структур мезолимбического дофаминергического пути – вентральном тегментуме, который является частью системы вознаграждения.

The incidence of autistic spectrum disorders (ASD) constantly increases in the world. Studying the mechanisms underlying ASD as well as searching for new therapeutic targets are crucial tasks. Many researchers agree that autism is a neurodevelopmental disorder. Clstn2-KO mouse strain with a knockout of calsyntenin 2 gene (Clstn2) is model for investigating ASD. This study aims to evaluate the social-conditioned place preference as well as density of dopaminergic (DA) neurons in the ventral tegmental area (VTA), which belongs to the brain reward system, in the males of the Clstn2-KO strain using wild type C57BL/6J males as controls. Social-conditioned place preference test evaluates a reward-dependent component of social behavior. The results of this test revealed differences between the Clstn2-KO and the control males, as the former did not value socializing with the familiar partner, spending equal time in the isolationand socializing-associated compartments. The Clstn2-KO group entered both compartments more frequently, but spent less time in the socializingassociated compartment compared to the controls. By contrast, the control males of the C57BL/6J strain spent more time in socializing-associated compartment and less time in the compartment that was associated with loneness. At the same time, an increased number of DA and possibly GABA neurons labeled with antibodies against the type 2 dopamine receptor as well as against tyrosine hydroxylase were detected in the VTA of the Clstn2-KO mice. Thus, a change in social-conditioned place preference in Clstn2-KO mice as well as a higher number of neurons expressing type 2 dopamine receptors and tyrosine hydroxylase in the VTA, the key structure of the mesolimbic dopaminergic pathway, were observed.

мыши Clstn2-KOсоциальное вознаграждениемозгвентральный тегментумдофаминергические нейроныClstn2-KO micesocial behaviorbrainventral tegmental areadopaminergic neuronsThe work was partially funded by the budget project No. FWNR-2022-0023 of the Institute of Cytology and Genetics SB RAS (Novosibirsk, Russia) and the Russian Foundation for Basic Research (No. 20-015-00162). The studies were performed using the equipment of the Center for Genetic Resources of Laboratory Animals of the Federal Research Center of the Institute of Cytology and Genetics of the Siberian Branch of the Russian Academy of Sciences, supported by the Ministry of Science and Higher Education of the Russian Federation (Unique identifier of the project RFMEFI62119X0023) and the Center for Microscopic Analysis of Biological Objects of the Siberian Branch of the Russian Academy of Sciences. The authors are grateful to T.N. 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The authors declare that there are no conflicts of interest present.