Hattori Satoko, Takao Keizo, Funakoshi Hiroshi, Miyakawa Tsuyoshi
Division of Systems Medical Science, Institute for Comprehensive Medical Science, Fujita Health University, Toyoake, Aichi, Japan.
Division of Animal Resources and Development, Life Science Research Center, University of Toyama, Toyama, Japan.
Neuropsychopharmacol Rep. 2018 Jun;38(2):52-60. doi: 10.1002/npr2.12006. Epub 2018 Mar 15.
Tryptophan 2,3-dioxygenase (TDO2) is an initial rate-limiting enzyme of the kynurenine (Kyn) pathway in tryptophan (Trp) metabolism. The Trp-degrading enzymes, TDO2 and indoleamine 2,3-dioxygenase, are activated by stress and/or inflammation. Dysregulation of Trp metabolism, which causes shifts in the balance between Kyn and serotonin (5-HT) pathways, is associated with psychiatric and neurological disorders. In genetic studies, single-nucleotide polymorphisms in the TDO2 gene were shown to be involved in psychiatric disorders, such as schizophrenia and depression. It has been reported that targeted deletion of the Tdo2 gene in mice resulted in reduced anxiety-like behavior, enhanced exploratory activity and cognitive performance, and increased levels of Trp and 5-HT in the hippocampus and midbrain. However, the effect of Tdo2 gene deletion on behavioral phenotypes has not yet been investigated extensively.
MATERIALS & METHODS: We conducted tests to further examine the behavioral effects of knockout (KO) of Tdo2 in mice.
Deletion of Tdo2 resulted in seemingly lower anxiety-like behavior, higher locomotor activity, and abnormal gait pattern in mice, though none of them reached study-wide statistical significance. Tdo2 deficiency had no significant effects on other behaviors, such as prepulse inhibition, and depression-like and social behaviors.
He lack of clear phenotypes in Tdo2KO mice in this study might be due to the absence of stress and inflammatory conditions, which could induce expression of Tdo2 mRNA. Further studies are necessary to elucidate the roles of Tdo2 in behavioral phenotypes related to psychiatric disorders.
色氨酸2,3-双加氧酶（TDO2）是色氨酸（Trp）代谢中犬尿氨酸（Kyn）途径的初始限速酶。Trp降解酶TDO2和吲哚胺2,3-双加氧酶可被应激和/或炎症激活。Trp代谢失调会导致Kyn和5-羟色胺（5-HT）途径之间的平衡发生变化，这与精神和神经疾病有关。在基因研究中，TDO2基因的单核苷酸多态性被证明与精神疾病有关，如精神分裂症和抑郁症。据报道，在小鼠中靶向缺失Tdo2基因会导致焦虑样行为减少、探索活动和认知能力增强，以及海马体和中脑Trp和5-HT水平升高。然而，Tdo2基因缺失对行为表型的影响尚未得到广泛研究。
我们进行了测试，以进一步研究敲除（KO）小鼠Tdo2后的行为影响。
Tdo2缺失导致小鼠出现看似较低的焦虑样行为、较高的运动活性和异常步态模式，尽管这些均未达到全研究范围的统计学显著性。Tdo2缺乏对其他行为没有显著影响，如前脉冲抑制、抑郁样行为和社交行为。
本研究中Tdo2基因敲除小鼠缺乏明确的表型可能是由于缺乏可诱导Tdo2 mRNA表达的应激和炎症条件。有必要进一步研究以阐明Tdo2在与精神疾病相关的行为表型中的作用。
