Gevorgyan M M, Zhanaeva S Ya, Alperina E L, Lipina T V, Idova G V
Scientific Research Institute of Physiology and Basic Medicine, Novosibirsk, Russia.
Vavilovskii Zhurnal Genet Selektsii. 2020 Nov;24(7):770-776. doi: 10.18699/VJ20.672.
The DISC1 (disrupted in sсhizophrenia 1) gene is associated with brain dysfunctions, which are involved in a variety of mental disorders, such as schizophrenia, depression and bipolar disorder. This is the first study to examine the immune parameters in Disc1-Q31L mice with a point mutation in the second exon of the DISC1 gene compared to mice of the C57BL/6NCrl strain (WT, wild type). A flow cytometry assay has shown that intact Disc1- Q31L mice differ from the WT strain by an increase in the percentage of CD3+ T cells, CD3+CD4+ Т helper cells and CD3+CD4+CD25+ T regulatory cells and a decrease in CD3+CD8+ T cytotoxic/suppressor cells in the peripheral blood. A multiplex analysis revealed differences in the content of cytokines in the brain structures of Disc1-Q31L mice compared to WT mice. The content of pro-inflammatory cytokines was increased in the frontal cortex (IL-6, IL- 17 and IFNγ) and striatum (IFNγ), and decreased in the hippocampus and hypothalamus. At the same time, the levels of IL-1β were decreased in all structures being examined. In addition, the content of anti-inflammatory cytokines IL-4 was increased in the frontal cortex, while IL-10 amount was decreased in the hippocampus. Immune response to sheep red blood cells analyzed by the number of antibody-forming cells in the spleen was higher in Disc1-Q31L mice at the peak of the reaction than in WT mice. Thus, Disc1-Q31L mice are characterized by changes in the pattern of cytokines in the brain structures, an amplification of the peripheral T-cell link with an increase in the content of the subpopulations of CD3+CD4+ T helpers and CD3+CD4+CD25+ T regulatory cells, as well as elevated immune reactivity to antigen in the spleen.
DISC1（精神分裂症1号染色体上的断裂基因）基因与大脑功能障碍有关，这些功能障碍涉及多种精神疾病，如精神分裂症、抑郁症和双相情感障碍。这是第一项研究，旨在检测与C57BL/6NCrl品系小鼠（WT，野生型）相比，DISC1基因第二外显子存在点突变的Disc1-Q31L小鼠的免疫参数。流式细胞术分析表明，完整的Disc1-Q31L小鼠与WT品系不同，其外周血中CD3+T细胞、CD3+CD4+辅助性T细胞和CD3+CD4+CD25+调节性T细胞的百分比增加，而CD3+CD8+细胞毒性/抑制性T细胞减少。多重分析显示，与WT小鼠相比，Disc1-Q31L小鼠脑结构中细胞因子的含量存在差异。额叶皮质（IL-6、IL-17和IFNγ）和纹状体（IFNγ）中促炎细胞因子的含量增加，而海马体和下丘脑则减少。同时，在所检测的所有结构中，IL-1β水平均降低。此外，额叶皮质中抗炎细胞因子IL-4的含量增加，而海马体中IL-10的含量减少。通过脾脏中抗体形成细胞数量分析的对绵羊红细胞的免疫反应，在反应高峰期，Disc1-Q31L小鼠比WT小鼠更高。因此，Disc1-Q31L小鼠的特征在于脑结构中细胞因子模式的变化、外周T细胞连接的扩增以及CD3+CD4+辅助性T细胞和CD3+CD4+CD25+调节性T细胞亚群含量的增加，以及脾脏对抗原的免疫反应性升高。
