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积极战斗经历及其随后剥夺对与神经发生相关的小鼠海马基因表达谱的影响。

Effects of Positive Fighting Experience and Its Subsequent Deprivation on the Expression Profile of Mouse Hippocampal Genes Associated with Neurogenesis.

机构信息

Federal Research Center, Institute of Cytology and Genetics, Siberian Branch of Russian Academy of Sciences, Novosibirsk 630090, Russia.

Pavlov Institute of Physiology, Russian Academy of Sciences, Saint Petersburg 199034, Russia.

出版信息

Int J Mol Sci. 2023 Feb 3;24(3):3040. doi: 10.3390/ijms24033040.

DOI:10.3390/ijms24033040
PMID:36769363
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9918130/
Abstract

The hippocampus is known as the brain region implicated in visuospatial processes and processes associated with learning and short- and long-term memory. An important functional characteristic of the hippocampus is lifelong neurogenesis. A decrease or increase in adult hippocampal neurogenesis is associated with a wide range of neurological diseases. We have previously shown that in adult male mice with a chronic positive fighting experience in daily agonistic interactions, there is an increase in the proliferation of progenitor neurons and the production of young neurons in the dentate gyrus (in hippocampus), and these neurogenesis parameters remain modified during 2 weeks of deprivation of further fights. The aim of the present work was to identify hippocampal genes associated with neurogenesis and involved in the formation of behavioral features in mice with the chronic experience of wins in aggressive confrontations, as well as during the subsequent 2-week deprivation of agonistic interactions. Hippocampal gene expression profiles were compared among three groups of adult male mice: chronically winning for 20 days in the agonistic interactions, chronically victorious for 20 days followed by the 2-week deprivation of fights, and intact (control) mice. Neurogenesis-associated genes were identified whose transcription levels changed during the social confrontations and in the subsequent period of deprivation of fights. In the experimental males, some of these genes are associated with behavioral traits, including abnormal aggression-related behavior, an abnormal anxiety-related response, and others. Two genes encoding transcription factors ( and ) were likely to contribute the most to the between-group differences. It can be concluded that the chronic experience of wins in agonistic interactions alters hippocampal levels of transcription of multiple genes in adult male mice. The transcriptome changes get reversed only partially after the 2-week period of deprivation of fights. The identified differentially expressed genes associated with neurogenesis and involved in the control of a behavior/neurological phenotype can be used in further studies to identify targets for therapeutic correction of the neurological disturbances that develop in winners under the conditions of chronic social confrontations.

摘要

海马体是已知与视空间过程以及与学习和短期及长期记忆相关的过程有关的脑区。海马体的一个重要功能特征是终生神经发生。成年海马神经发生的减少或增加与广泛的神经退行性疾病有关。我们之前已经表明,在成年雄性小鼠中,日常搏斗互动中的慢性积极战斗经历会导致齿状回(海马体)中的祖细胞神经元增殖和新生神经元产生增加,并且这些神经发生参数在 2 周剥夺进一步战斗后仍保持改变。本研究的目的是鉴定与神经发生相关的海马基因,并确定在慢性经历攻击性对抗胜利的小鼠中,以及在随后的 2 周剥夺搏斗期间,这些基因与行为特征的形成有关。比较了三组成年雄性小鼠的海马基因表达谱:在搏斗中慢性获胜 20 天、慢性胜利 20 天并随后剥夺搏斗 2 周以及完整(对照)小鼠。鉴定了在社会对抗期间和随后的战斗剥夺期间转录水平发生变化的与神经发生相关的基因。在实验组雄性小鼠中,其中一些基因与行为特征有关,包括异常的攻击相关行为、异常的焦虑相关反应等。两个编码转录因子(和)的基因可能对组间差异的贡献最大。可以得出结论,在搏斗中慢性胜利的经历改变了成年雄性小鼠海马体中多个基因的转录水平。在剥夺战斗 2 周后,转录组变化仅部分逆转。鉴定出的与神经发生相关并参与行为/神经表型控制的差异表达基因可用于进一步研究,以确定在慢性社会对抗条件下获胜者中出现的神经紊乱的治疗校正靶点。

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