Bazhenova Ekaterina Y, Sinyakova Nadezhda A, Kulikova Elizabeth A, Kazarinova Irina A, Bazovkina Daria V, Gainetdinov Raul R, Kulikov Alexander V
Department of Genetic Models of Neuropathologies, Federal Research Center Institute of Cytology and Genetics, Siberian Division of the Russian Academy of Science, Novosibirsk, 630090, Russia.
Department of Genetic Models of Neuropathologies, Federal Research Center Institute of Cytology and Genetics, Siberian Division of the Russian Academy of Science, Novosibirsk, 630090, Russia.
Neurosci Lett. 2017 Jul 13;653:264-268. doi: 10.1016/j.neulet.2017.05.070. Epub 2017 Jun 1.
Selective serotonin reuptake inhibitors (SSRIs) are antidepressants that block serotonin transporter (SERT) and increase serotonin (5-HT) level in the synaptic cleft. The interaction between SERT and the key enzyme of 5-HT synthesis in the brain, tryptophan hydroxylase 2 (TPH2), is essential to maintain the brain 5-HT level. The G allele of C1473G polymorphism in Tph2 gene decreases enzyme activity by half in mouse brain. Here we studied effect of C1473G polymorphism on the reaction of brain 5-HT system to chronic fluoxetine treatment (120mg/l in drinking water, for 3 weeks) in adult males of the congenic B6-1473C and B6-1473G mouse lines with high and low enzyme activity, respectively. The polymorphism did not affect the levels of 5-HT, its metabolite, 5-hydroxyindoleacetic acid (5-HIAA) and Tph2 gene mRNA in the brain. Fluoxetine significantly attenuated 5-HT levels in the cortex and striatum, 5-HIAA concentrations in the cortex, hippocampus, striatum and midbrain, and Tph2 gene expression in the midbrain. However, we did not observed any effect of the genotype x treatment interaction on these neurochemical characteristics. Therefore, C1473G polymorphism does not seem to play an essential role in the reaction of the brain 5-HT system to chronic fluoxetine treatment.
选择性5-羟色胺再摄取抑制剂（SSRIs）是一类抗抑郁药，可阻断5-羟色胺转运体（SERT），提高突触间隙中5-羟色胺（5-HT）的水平。SERT与大脑中5-HT合成的关键酶色氨酸羟化酶2（TPH2）之间的相互作用对于维持大脑5-HT水平至关重要。Tph2基因C1473G多态性的G等位基因可使小鼠大脑中的酶活性降低一半。在此，我们研究了C1473G多态性对分别具有高酶活性和低酶活性的同基因B6-1473C和B6-1473G小鼠品系成年雄性小鼠大脑5-HT系统对慢性氟西汀治疗（饮用水中含120mg/l，持续3周）反应的影响。该多态性不影响大脑中5-HT、其代谢产物5-羟吲哚乙酸（5-HIAA）的水平以及Tph2基因的mRNA水平。氟西汀显著降低了皮质和纹状体中的5-HT水平、皮质、海马体、纹状体和中脑中的5-HIAA浓度以及中脑中Tph2基因的表达。然而，我们未观察到基因型x治疗相互作用对这些神经化学特征有任何影响。因此，C1473G多态性似乎在大脑5-HT系统对慢性氟西汀治疗的反应中不起重要作用。
