Miura Hideki, Shirokawa Tetsuya, Isobe Kenichi, Ozaki Norio
Department of Psychiatry, Nagoya University Graduate School of Medicine, Nagoya, Aichi, Japan.
Stress. 2009 May;12(3):206-14. doi: 10.1080/10253890802252442.
The kynurenine (KYN) pathway, which is initiated by indoleamine 2,3-dioxygenase, is a key tryptophan (TRP) metabolic pathway. It shares TRP mainly with the serotonin (5-HT) pathway. Activation of the KYN pathway by stimulation of the inflammatory response system (IRS) is known to induce depressive symptoms. Thus, we considered that shifting the balance between the KYN and 5-HT systems in the brain to the KYN pathway closely relate to the etiology of depression. In the present study, we investigated the influence of environmental risk factors for depression, such as social isolation and activation of the IRS, on brain TRP metabolism. Male ICR mice (postnatal day 21) were divided into two housing conditions, isolation and group housing, reared for 4 weeks, and then given an intraperitoneal injection of lipopolysaccharide (LPS). We measured the TRP, KYN, and 5-HT levels in the prefrontal cortex, hippocampus, amygdala, and dorsal raphe nuclei. Isolation housing decreased the KYN/5-HT ratio in the amygdala and dorsal raphe nuclei. LPS increased the KYN/5-HT ratio in all regions except the dorsal raphe nuclei. Thus, isolation housing shifted the balance between the KYN and 5-HT pathways to the 5-HT pathway, whereas systemic administration of LPS shifted it to the KYN pathway.
犬尿氨酸（KYN）途径由吲哚胺2,3-双加氧酶启动，是色氨酸（TRP）的关键代谢途径。它主要与血清素（5-HT）途径共享TRP。已知通过刺激炎症反应系统（IRS）激活KYN途径会诱发抑郁症状。因此，我们认为大脑中KYN和5-HT系统之间的平衡向KYN途径的转变与抑郁症的病因密切相关。在本研究中，我们调查了抑郁症的环境危险因素，如社会隔离和IRS激活，对大脑TRP代谢的影响。雄性ICR小鼠（出生后第21天）被分为两种饲养条件，隔离饲养和群居饲养，饲养4周，然后腹腔注射脂多糖（LPS）。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水平。隔离饲养降低了杏仁核和中缝背核中的KYN/5-HT比值。LPS增加了除中缝背核以外所有区域的KYN/5-HT比值。因此，隔离饲养将KYN和5-HT途径之间的平衡转向了5-HT途径，而全身注射LPS则将其转向了KYN途径。
