Kudryavtseva N N, Smagin D A, Kovalenko I L, Galyamina A G, Vishnivetskaya G B, Babenko V N, Orlov Yu L
Institute of Cytology and Genetics, Siberian Branch of Russian Academy of Sciences, Novosibirsk, 630090 Russia.
Mol Biol (Mosk). 2017 Mar-Apr;51(2):288-300. doi: 10.7868/S0026898417020136.
In course of daily agonistic interactions, mice tend to stratify into those with chronic social defeats and those that repeatedly display aggression, which lead to the development of mixed anxiety/depression-like state and the pathology of aggressive behavior, respectively. Using the data of whole transcriptome analysis (RNA-seq), the changes in the expression of serotonergic genes involved in the synthesis, inactivation, and reception of serotonin, as well as of the Creb1 (transcription factor) gene and the Bdnf (brain-derived neurotrophic factor) gene were detected in the striatum (STR), ventral tegmental area (VTA), midbrain raphe nuclei (MRN), hypothalamus (HYP), and hippocampus (HIP) of defeated and aggressive male mice. In mice of both groups, the Tph2, Ddc, Slc6a4, Htr2a, Htr3a, Htr5b, Slc18a2, and Bdnf genes were downregulated in the MRN and the Tph2, Ddc, and Slc6a4 genes were upregulated in the VTA. These changes were more significant in defeated mice. The Htr5b gene has first been shown to be involved in mechanisms of depression and pathology of aggressive behavior. In the defeated mice, the expression levels of the Htr4 and Aldh1b1 genes were increased in the MRN, and expression levels of the Maob, Htr4, Htr1a, and Slc18a2 genes were increased in the VTA, while the expression level of the Htr3a gene was decreased. In the HYP of aggressive mice the Maoa, Htr2a, Htr2c, and Creb1 genes were downregulated and the Htr6 gene was upregulated. In the defeated mice, the Maoa and Creb1 genes were downregulated and the Htr6 and Aldh1b1 genes were upregulated in the HYP. In the STR, the Htr1a gene was downregulated and the Htr7 and Bdnf genes were upregulated. The Htr1b gene was upregulated in the HIP. The coexpression of dopaminergic and serotonergic genes in the MRN and VTA in the control of pathological behaviors is discussed. Thus, the complex pattern of differential expression of serotonergic genes in brain regions developing under repeated agonistic interactions in mice in dependence on behavioral pathology have been observed.
在日常的对抗性互动过程中,小鼠往往会分为遭受慢性社会挫败的小鼠和反复表现出攻击性的小鼠,这分别导致混合性焦虑/抑郁样状态的发展和攻击行为的病理变化。利用全转录组分析(RNA测序)的数据,在遭受挫败和具有攻击性的雄性小鼠的纹状体(STR)、腹侧被盖区(VTA)、中脑缝际核(MRN)、下丘脑(HYP)和海马体(HIP)中,检测了参与血清素合成、失活和受体作用的血清素能基因以及Creb1(转录因子)基因和Bdnf(脑源性神经营养因子)基因的表达变化。在两组小鼠中,Tph2、Ddc、Slc6a4、Htr2a、Htr3a、Htr5b、Slc18a2和Bdnf基因在MRN中下调,Tph2、Ddc和Slc6a4基因在VTA中上调。这些变化在遭受挫败的小鼠中更为显著。首次发现Htr5b基因参与抑郁机制和攻击行为的病理过程。在遭受挫败的小鼠中,Htr4和Aldh1b1基因在MRN中的表达水平升高,Maob、Htr4、Htr1a和Slc18a2基因在VTA中的表达水平升高,而Htr3a基因的表达水平降低。在具有攻击性的小鼠的HYP中,Maoa、Htr2a、Htr2c和Creb1基因下调,Htr6基因上调。在遭受挫败的小鼠中,Maoa和Creb1基因在HYP中下调,Htr6和Aldh1b1基因上调。在STR中,Htr1a基因下调,Htr7和Bdnf基因上调。Htr1b基因在HIP中上调。讨论了多巴胺能和血清素能基因在MRN和VTA中的共表达对病理行为的控制作用。因此,观察到了小鼠在反复的对抗性互动下,根据行为病理情况,脑区中血清素能基因差异表达的复杂模式。