Tryptophan 2,3-dioxygenase is a key modulator of physiological neurogenesis and anxiety-related behavior in mice

被引：227

作者：

Kanai, Masaaki ^{[1
]}

Funakoshi, Hiroshi ^{[1
]}

Takahashi, Hisaaki ^{[1
,2
]}

Hayakawa, Tomoko ^{[1
,3
]}

Mizuno, Shinya ^{[1
]}

Matsumoto, Kunio ^{[1
,4
]}

Nakamura, Toshikazu ^{[1
,5
]}

机构：

[1] Osaka Univ, Grad Sch Med, Dept Biochem & Mol Biol, Div Mol Regenerat Med, Suita, Osaka 5650871, Japan

[2] Ehime Univ, Sch Med, Dept Mol & Cellular Biol, Matsuyama, Ehime 790, Japan

[3] Univ Tokyo, Grad Sch Med, Dept Vasc Regenerat, Tokyo, Japan

[4] Kanazawa Univ, Canc Res Inst, Div Tumor Dynam & Regulat, Kanazawa, Ishikawa 920, Japan

[5] Osaka Univ, Kringle Pharma Joint Res Div Regenerat Drug Disco, Suita, Osaka 5650871, Japan

来源：

MOLECULAR BRAIN | 2009年 / 2卷

关键词：

Neural Progenitor; Open Field Test; Kynurenine; Adult Neurogenesis; Kynurenine Pathway;

D O I：

10.1186/1756-6606-2-8

中图分类号：

Q189 [神经科学];

学科分类号：

071006 ;

摘要：

Although nutrients, including amino acids and their metabolites such as serotonin (5-HT), are strong modulators of anxiety-related behavior, the metabolic pathway(s) responsible for this physiological modulation is not fully understood. Regarding tryptophan (Trp), the initial rate-limiting enzymes for the kynurenine pathway of tryptophan metabolism are tryptophan 2,3-dioxygenase (TDO) and indoleamine 2,3-dioxygenase (IDO). Here, we generated mice deficient for tdo (Tdo(-/-)). Compared with wild-type littermates, Tdo(-/-)mice showed increased plasma levels of Trp and its metabolites 5-hydroxyindoleacetic acid (5-HIAA) and kynurenine, as well as increased levels of Trp, 5-HT and 5-HIAA in the hippocampus and midbrain. These mice also showed anxiolytic modulation in the elevated plus maze and open field tests, and increased adult neurogenesis, as evidenced by double staining of BrdU and neural progenitor/neuronal markers. These findings demonstrate a direct molecular link between Trp metabolism and neurogenesis and anxiety-related behavior under physiological conditions.

引用

页数：16

共 54 条

[1] Early-life blockade of the 5-HT transporter alters emotional behavior in adult mice [J].