FRC Institute of Cytology and Genetics, Siberian Branch of Russian Academy of Sciences, 630090 Novosibirsk, Russia.
Pavlov Institute of Physiology, Russian Academy of Sciences, 199034 Saint Petersburg, Russia.
Genes (Basel). 2021 Nov 18;12(11):1811. doi: 10.3390/genes12111811.
Midbrain raphe nuclei (MRNs) contain a large number of serotonergic neurons associated with the regulation of numerous types of psychoemotional states and physiological processes. The aim of this work was to study alterations of the MRN transcriptome in mice with prolonged positive or negative fighting experience and to identify key gene networks associated with the regulation of serotonergic system functioning. Numerous genes underwent alterations of transcription in the MRNs of male mice that either manifested aggression or experienced social defeat in daily agonistic interactions. The expression of the gene encoding the rate-limiting enzyme of the serotonin synthesis pathway correlated with the expression of many genes, 31 of which were common between aggressive and defeated mice and were downregulated in the MRNs of mice of both experimental groups. Among these common differentially expressed genes (DEGs), there were genes associated with behavior, learning, memory, and synaptic signaling. These results suggested that, in the MRNs of the mice, the transcriptome changes associated with serotonergic regulation of various processes are similar between the two groups (aggressive and defeated). In the MRNs, more DEGs correlating with expression were found in defeated mice than in the winners, which is probably a consequence of deeper downregulation in the losers. It was shown for the first time that, in both groups of experimental mice, the changes in the transcription of genes controlling the synthesis and transport of serotonin directly correlate with the expression of genes and , which control the synthesis of corticotrophin- and thyrotropin-releasing hormones. Our findings indicate that CRH and TRH locally produced in MRNs are related to serotonergic regulation of brain processes during a chronic social conflict.
中脑缝核（MRN）包含大量与调节多种心理情绪状态和生理过程相关的 5-羟色胺能神经元。本工作旨在研究具有长期积极或消极战斗经验的小鼠中 MRN 转录组的变化，并鉴定与 5-羟色胺能系统功能调节相关的关键基因网络。在每日争斗性相互作用中表现出攻击性或经历社会挫败的雄性小鼠的 MRN 中，许多基因的转录发生了改变。编码 5-羟色氨酸合成途径限速酶的 基因的表达与许多基因的表达相关，其中 31 个基因在攻击性和被击败的小鼠之间共表达，并在两个实验组小鼠的 MRN 中下调。在这些共同差异表达基因（DEGs）中，有与行为、学习、记忆和突触信号相关的基因。这些结果表明，在两组（攻击性和被击败）小鼠的 MRN 中，与各种过程的 5-羟色胺调节相关的转录组变化相似。在 MRN 中，与 表达相关的 DEGs 在被击败的小鼠中比在胜利者中更多，这可能是失败者中 下调更深的结果。首次表明，在两组实验小鼠中，控制 5-羟色胺合成和转运的基因转录变化与控制促肾上腺皮质激素和促甲状腺激素释放激素合成的基因 和 的表达直接相关。我们的研究结果表明，MRN 中局部产生的 CRH 和 TRH 与慢性社会冲突期间大脑过程的 5-羟色胺能调节有关。
