shifts in the balance of brain tryptophan metabolism due to age and systemic administration of lipopolysaccharide大脑的色氨酸代谢平衡的变化由于年龄和脂多糖的系统性管理.pdf

Vol.2, No.3, 225-233 (2010) Health doi:10.4236/health.2010.23032 Shifts in the balance of brain tryptophan metabolism due to age and systemic administration of lipopolysaccharide 1 2 1 3 Hideki Miura , Tetsuya Shirokawa , Norio Ozaki , Kenichi Isobe 1Department of Psychiatry, Nagoya University Graduate School of Medicine, Nagoya, Japan; hmiura@med.nagoya-u.ac.jp 2Department of Information Technology for Human Welfare, Nihon Fukushi University, Mihama, Japan 3Department of Immunology, Nagoya University Graduate School of Medicine, Nagoya, Japan Received 9 November 2009; revised 22 December 2009; accepted 24 December 2009. ABSTRACT 1. INTRODUCTION The kynurenine (KYN) pathway, which is initi- Changes in tryptophan (TRP) metabolism play an im- ated by indoleamine 2, 3-dioxygenase (IDO), is a portant role in the brain-endocrine-immune system in- key tryptophan (TRP) metabolic pathway. It teraction that is hypothesized to be involved in the eti- shares TRP with the serotonin (5-HT) pathway. ology and/or pathophysiology of major depression. Two Because activation of the KYN pathway by pro- main pathways metabolize TRP. One is the kynurenine inflammatory cytokines induces depressive (KYN) pathway, which is initiated by indoleamine 2, symptoms, shifts in the balance of TRP metabo- 3-dioxygenase (IDO). The other is the serotonin (5-HT) lism to the KYN pathway are clo