Molecular dissection of tryptophan metabolism in emotional behavior and its related is diseases.

色氨酸(Tryptophan，Trp)通过3条主要途径代谢：5-羟色胺(5-羟色胺)途径、转胺(Transamine)途径和肌动能(Kyn)途径，其中Kyn途径贡献了约95%的Trp代谢。因此，人们认为，阐明Kyn通路的作用可能会揭示Trp代谢在包括情绪行为在内的多种功能中的作用。然而，由于Kyn途径中存在两种限制性内切酶，限制了对这些酶在体内的分析。在这里，我们建立了TDO-KO小鼠，并阐明了TDO在(1)体循环和脑中的色氨酸代谢(2)色氨酸代谢(包括不同食物条件下的NAD)中的作用(3)更高的大脑功能和免疫功能以及(4)情绪疾病。

Tryptophan (Trp) is metabolized via there major pathways; the serotonergic , transaminergic and kynurenergic (Kyn) pathways, and the Kyn pathway contributes about 95% of Trp metabolism. Therefore it has been thought that the elucidation of the roles of Kyn pathway may unvail the roles of Trp metabolisms in a variety of functions, including emotional behaviors. However, because of the presence of two restriction enzymes in Kyn pathway, it has been limited for the analyses of these enzymes in vivo. Here we have generated TDO-KO mice and elucidated the roles of TDO in (1) tryptophan metabolism in the systemic circulation and brain (2) tryptophan metabolismsincluding NAD in different food conditions (3) higher brain function as well as immunological function and (4) emotional disease.