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Effect of the C1473G Polymorphic Variant of the Tryptophan Hydroxylase 2 Gene and Photoperiod Length on the Dopamine System of the Mouse Brain
Molecular Biology ( IF 1.2 ) Pub Date : 2020-02-25 , DOI: 10.1134/s0026893320010148
N. A. Sinyakova , E. Yu. Bazhenova , E. A. Kulikova , D. V. Fursenko , A. V. Kulikov

Abstract—

A decrease in the light in autumn and winter causes depression like seasonal affective disorders (SAD) in sensitive patients, in which the serotonin (5-HT) and dopamine (DA) brain mediator systems are involved. We studied the interaction of the 5-HT and DA brain systems in an experimental SAD model in sexually mature male mice of the congenic B6-1473C and B6-1473G lines with high and low activity of tryptophan hydroxylase 2, a key enzyme of 5-HT synthesis in the brain. Mice of each line (divided into two groups of eight individuals) were kept for 30 days in standard (14 h light/10 h dark) and short (4 h light/20 h dark) daylight. The presence of the C1473G variant in the tryptophan hydroxylase 2 gene did not affect the expression of key genes of DA system: Drd1, Drd2, Scl6a3, Th, and Comt, that encode the D1 and D2 receptors, dopamine transporter, tyrosine hydroxylase, and catechol-o-methyltransferase, respectively. A decrease in the level of DA in the midbrain, as well as of its metabolite 3,4-dihydroxyphenylacetic acid (DOPAC) in the striatum, was detected in B6-1473G mice. Keeping mice in short daylight did not affect expression of the Drd1 gene in all brain structures nor the expression of the Slc6a3 and Th genes in the midbrain. Drd2 expression increased in the midbrain and decreased in the hippocampus, where Comt expression increased. An increase in DA level in the midbrain and DOPAC in the striatum was detected in mice kept in short daylight. This indicates the involvement of the brain’s DA system in the reaction to a decrease in daylight duration. No statistically significant effect of the interaction between the presence of the C1473G variant and daylight length on indicators of the activity of DA system was detected. No reasons were found to assert that this polymorphism determines the observed reaction of the brain DA system in keeping of animals under short daylight conditions.


中文翻译:

色氨酸羟化酶2基因的C1473G多态性变体和光周期长度对小鼠脑多巴胺系统的影响。

摘要-

秋季和冬季光线的减少会引起敏感患者的抑郁,如季节性情感障碍(SAD),其中涉及5-羟色胺(5-HT)和多巴胺(DA)脑介导系统。我们在色氨酸羟化酶2(一种5-羟色胺的关键酶)的高和低活性的同基因B6-1473C和B6-1473G系的性成熟雄性小鼠的实验性SAD模型中研究了5-HT和DA脑系统的相互作用。大脑中的HT合成。将每行的小鼠(分为八人一组,分为两组)在标准(14小时光照/ 10小时黑暗)和短时(4小时光照/ 20小时黑暗)日光下保持30天。色氨酸羟化酶2基因中C1473G变体的存在不影响DA系统关键基因的表达:Drd1Drd2Scl6a3,和孔泰,D1和D2受体,多巴胺转运蛋白,酪氨酸羟化酶,和儿茶酚其编码ö分别-methyltransferase。在B6-1473G小鼠中检测到中脑DA及其纹状体中3,4-二羟基苯基乙酸(DOPAC)的代谢产物水平降低。保持小鼠在短时间内不影响所有大脑结构中Drd1基因的表达,也不影响中脑中Slc6a3Th基因的表达。DRD2表达中脑增加,在海马,在那里降低孔泰表达增加。在短日照下发现小鼠中脑中DA水平增加,纹状体中DOPAC升高。这表明大脑DA系统参与了对日光持续时间减少的反应。没有检测到C1473G变体的存在与日光长度之间的相互作用对DA系统活性指标的统计学显着影响。没有理由断言这种多态性决定了在短日照条件下饲养动物时大脑DA系统的观察反应。
更新日期:2020-02-25
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