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[色氨酸羟化酶2基因C1473G多态性变体及光照周期长度对小鼠脑多巴胺系统的影响]

[Effect of the C1473G Polymorphic Variant of the Tryptophan Hydroxylase 2 Gene and Photoperiod Length on the Dopamine System of the Mouse Brain].

作者信息

Sinyakova N A, Bazhenova E Yu, Kulikova E A, Fursenko D V, Kulikov A V

机构信息

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

出版信息

Mol Biol (Mosk). 2020 Jan-Feb;54(1):60-68. doi: 10.31857/S0026898420010140.

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.

摘要

秋冬季节光照减少会使敏感患者出现类似季节性情感障碍(SAD)的抑郁症状,其中涉及血清素(5-HT)和多巴胺(DA)脑调节系统。我们在同基因B6-1473C和B6-1473G品系的性成熟雄性小鼠实验性SAD模型中研究了5-HT和DA脑系统的相互作用,这两个品系中色氨酸羟化酶2(大脑中5-HT合成的关键酶)的活性高低不同。每个品系的小鼠(分为两组,每组八只)在标准(14小时光照/10小时黑暗)和短日照(4小时光照/20小时黑暗)条件下饲养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:Drd1、Drd2、Scl6a3、Th和Comt,它们分别编码D1和D2受体、多巴胺转运体、酪氨酸羟化酶和儿茶酚-O-甲基转移酶。在B6-1473G小鼠中检测到中脑DA水平以及纹状体中其代谢物3,4-二羟基苯乙酸(DOPAC)水平降低。将小鼠置于短日照条件下并不影响所有脑结构中Drd1基因的表达,也不影响中脑Slc6a3和Th基因的表达。中脑Drd2表达增加,海马体中Drd2表达减少,而海马体中Comt表达增加。在短日照条件下饲养的小鼠中检测到中脑DA水平和纹状体中DOPAC增加。这表明大脑DA系统参与了对日照时长减少的反应。未检测到C1473G变体的存在与日照长度之间的相互作用对DA系统活性指标有统计学上的显著影响。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系统的观察到的反应。

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