Miura Hideki, Ozaki Norio, Shirokawa Tetsuya, Isobe Kenichi
Department of Psychiatry, Nagoya University Graduate School of Medicine, Aichi, Japan.
Stress. 2008 Mar;11(2):160-9. doi: 10.1080/10253890701685908.
The kynurenine (KYN) pathway, which is initiated by indoleamine 2,3-dioxygenase (IDO), is a tryptophan (TRP) metabolic pathway. It shares TRP with the serotonin (5-hydroxytryptamine, 5-HT) pathway. In major depression, activation of the KYN pathway may deplete 5-HT. In the present study we investigated the influence of various risk factors for depression, such as ageing, social isolation and psychological stress, on TRP metabolism. Male ICR mice (postnatal day, PND, 21) were divided into two housing conditions, isolation and group housing, reared for 4 weeks (young adult) or 5 months (adult) and exposed to novelty stress. We measured TRP, KYN and 5-HT contents in the prefrontal cortex, hippocampus, amygdala and dorsal raphe nuclei to investigate the balance between the KYN and 5-HT pathways. Ageing decreased TRP and KYN and increased 5-HT. Thus, ageing shifted the balance to the latter. In the younger group, social isolation decreased TRP and KYN and increased the 5-HT/TRP ratio, whereas novelty stress increased TRP and KYN and decreased the 5-HT/TRP ratio. Thus, social isolation shifted the balance to the latter, whereas novelty stress shifted it to the former. In the older group, these effects were restricted to specific brain regions. Ageing and social isolation counteracted novelty stress effects on TRP metabolism.
犬尿氨酸（KYN）途径由吲哚胺2,3-双加氧酶（IDO）启动，是一条色氨酸（TRP）代谢途径。它与血清素（5-羟色胺，5-HT）途径共用TRP。在重度抑郁症中，KYN途径的激活可能会消耗5-HT。在本研究中，我们调查了抑郁症的各种风险因素，如衰老、社会隔离和心理压力，对TRP代谢的影响。雄性ICR小鼠（出生后天数，PND，21）被分为两种饲养条件，隔离饲养和群居饲养，饲养4周（年轻成年）或5个月（成年），并暴露于新奇应激。我们测量了前额叶皮质、海马体、杏仁核和中缝背核中的TRP、KYN和5-HT含量，以研究KYN和5-HT途径之间的平衡。衰老降低了TRP和KYN，增加了5-HT。因此，衰老使平衡转向后者。在较年轻的组中，社会隔离降低了TRP和KYN，并增加了5-HT/TRP比值，而新奇应激增加了TRP和KYN，并降低了5-HT/TRP比值。因此，社会隔离使平衡转向后者，而新奇应激使平衡转向前者。在较年长的组中，这些影响仅限于特定的脑区。衰老和社会隔离抵消了新奇应激对TRP代谢的影响。
