vavilovВавиловский журнал генетики и селекцииVavilov Journal of Genetics and Breeding2500-3259Institute of Cytology and Genetics of Siberian Branch of the RAS10.18699/VJGB-23-76vavilov-3937Research ArticleГЕНЕТИКА ЖИВОТНЫХANIMAL GENETICSПрофиль экспрессии генов, связанных с регуляцией стресса, поведения и нейрогенеза, вдоль дорзовентральной оси в гиппокампе у взрослых ручных и агрессивных лисицThe expression profile of genes associated with behavior, stress, and adult neurogenesis along the hippocampal dorsoventral axis in tame and aggressive foxesАлександровичЮ. В.AlexandrovichYu. V.

Новосибирск

Novosibirsk

АнтоновЕ. В.AntonovE. V.

Новосибирск; Сочи

Novosibirsk; Sochi

ШихевичС. Г.ShikhevichS. G.

Новосибирск

Novosibirsk

ХарламоваА. В.KharlamovaA. V.

Новосибирск

Novosibirsk

МейстерЛ. В.MeisterL. V.

Новосибирск

Novosibirsk

МаковкаЮ. В.MakovkaY. V.

Новосибирск

Novosibirsk

ШепелеваД. В.ShepelevaD. V.

Новосибирск

Novosibirsk

ГулевичР. Г.GulevichR. G.

Новосибирск

Novosibirsk

gulevich@bionet.nsc.ruГербекЮ. Э.HerbeckYu. E.

Школа ветеринарной медицины им. Й. Корета, Факультет сельского хозяйства, продовольственных ресурсов и окружающей среды им. Р.Г. Смита, Еврейский университет в Иерусалиме

Новосибирск; Реховот

Koret School of Veterinary Medicine, The Robert H. Smith Faculty of Agriculture, Food and Environment, The Hebrew University of Jerusalem.

Novosibirsk; Rehovot

Федеральный исследовательский центр Институт цитологии и генетики Сибирского отделения Российской академии наукРоссияInstitute of Cytology and Genetics of the Siberian Branch of the Russian Academy of SciencesRussian FederationФедеральный исследовательский центр Институт цитологии и генетики Сибирского отделения Российской академии наук; Научно-технологический университет «Сириус», Научный центр трансляционной медициныРоссияInstitute of Cytology and Genetics of the Siberian Branch of the Russian Academy of Sciences; Sirius University of Science and Technology, Scientific Center for Translational MedicineRussian FederationФедеральный исследовательский центр Институт цитологии и генетики Сибирского отделения Российской академии наук; Еврейский университет в ИерусалимеРоссияInstitute of Cytology and Genetics of the Siberian Branch of the Russian Academy of Sciences; The Hebrew University of JerusalemRussian Federation202302112023276651661Copyright © Александрович Ю.В., Антонов Е.В., Шихевич С.Г., Харламова А.В., Мейстер Л.В., Маковка Ю.В., Шепелева Д.В., Гулевич Р.Г., Гербек Ю.Э., 20232023Александрович Ю.В., Антонов Е.В., Шихевич С.Г., Харламова А.В., Мейстер Л.В., Маковка Ю.В., Шепелева Д.В., Гулевич Р.Г., Гербек Ю.Э.Alexandrovich Y.V., Antonov E.V., Shikhevich S.G., Kharlamova A.V., Meister L.V., Makovka Y.V., Shepeleva D.V., Gulevich R.G., Herbeck Y.E.This work is licensed under a Creative Commons Attribution 4.0 License.https://vavilov.elpub.ru/jour/article/view/3937

Гиппокамп является ключевой структурой в регуляции стресс-ответа, который, по-видимому, снижен у домашних животных по сравнению с их дикими сородичами. Известно, что гиппокамп функционально неоднороден вдоль дорзовентральной оси, и в регуляции стресса в большей мере участвует вентральная часть. В серии экспериментов на уникальной селекционной модели одомашнивания животных – серебристо-черной лисице (Vulpes vulpes), включающей ручных, агрессивных и неселекционированных животных, ранее было показано снижение активности гипоталамо-гипофизарно-надпочечниковой системы во многих звеньях. Кроме того, известно, что уровень нейрогенеза в гиппокампе повышен у взрослых ручных лисиц, что может быть взаимосвязано со снижением уровня стресса. Тем не менее молекулярно-генетические механизмы снижения стресс-ответа у доместицированных животных по-прежнему не ясны. В настоящей работе выполнено сравнение мРНК 13 генов в дорзальном и вентральном гиппокампе и проведен анализ кортизола в крови у ручных, агрессивных и неселекционированных лисиц. Установлено, что на данном этапе доместикации стресс-индуцированный уровень кортизола у ручных, агрессивных и неселекционированных животных достоверно отличается друг от друга, причем у ручных животных он самый низкий, а у агрессивных – самый высокий. Выявлены достоверные различия в экспрессии 12 генов между дорзальной и вентральной частями гиппокампа, что в большинстве случаев соответствует аналогичным различиям, найденным у грызунов и человека. У ручных лисиц обнаружен достоверно повышенный уровень в дорзальном гиппокампе мРНК генов цитохрома P450 26B1 (CYP26B1) и адренергического рецептора α1A (ADRA1A), а в вентральном гиппокампе – мРНК гена минералокортикоидного рецептора (NR3C2). Эти гены могут быть важной частью механизма снижения стресса по отношению к человеку и взаимосвязи регуляции стресса и нейрогенеза у взрослых ручных лисиц в частности и доместицированных животных вообще.

The hippocampus plays the key role in stress response regulation, and stress response appears to be weakened in domesticated animals compared to their wild relatives. The hippocampus is functionally heterogeneous along its dorsoventral axis, with its ventral compartment being more closely involved in stress regulation. An earlier series of experiments was conducted with a unique breeding model of animal domestication, the farm silver fox (Vulpes vulpes), which included tame, aggressive, and unselected animals. A decrease in many indices of the hypothalamic–pituitary–adrenal activity was observed in tame animals. Also, adult hippocampal neurogenesis was more intense in tame foxes, and this fact may relate to reduced stress levels in this experimental population of foxes. Nevertheless, the molecular mechanisms responsible for the reduced stress response in tame animals remain obscure. In this study, serum cortisol levels and the mRNA levels of 13 genes in the dorsal and ventral hippocampus have been measured and compared in tame, aggressive, and unselected foxes. At the current stage of domestication, stress-induced cortisol levels in tame, aggressive, and unselected animals differ significantly from each other: tame foxes show the lowest levels, and aggressive ones, the highest. Twelve genes tested demonstrate significant gene expression differences between the dorsal and ventral hippocampi. These differences are mainly consistent with those found in rodents and humans. In tame foxes, significantly elevated mRNA levels were recorded for several genes: CYP26B1 for cytochrome P450 26B1 and ADRA1A for α1A adrenergic receptor in the dorsal hippocampus, whereas the level of NR3C2 mRNA for mineralocorticoid receptor was higher in the ventral. It is presumed that these genes constitute an important part of the mechanism reducing stress induced by contacts with humans and contribute to linking stress regulation with adult neurogenesis in tame foxes and domesticated animals in general.

ручное поведениеагрессиядоместикациясеребристо-черные лисицыкортизолtame behavioraggressiondomesticationsilver foxcortisolThis work was supported by the Russian Science Foundation, project 21-44-04405. The breeding of experimental animals in the Shared Access Center for Gene Pools of Fur and Farm Animals, Institute of Cytology and Genetics, was supported by State Budgeted Project FWNR- 2022- 0019. The authors are grateful to V.V. Ivaykin, A.V. Vladimirova, I.V. Pivovarova, T.I. Semenova, V.I. Vladimirova, T.V. Konovalova, and all the staff of the Shared Access Center for assistance in the study. They also acknowledge the significant contribution of the reviewers to manuscript improvementReferencesAmrein I. Adult hippocampal neurogenesis in natural populations of mammals. Cold Spring Harb. Perspect. Biol. 2015;7(5):a021295. DOI: 10.1101/cshperspect.a021295.Amrein I. Adult hippocampal neurogenesis in natural populations of mammals. Cold Spring Harb. Perspect. Biol. 2015;7(5):a021295. 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The authors declare that there are no conflicts of interest present.