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

情绪行为及其相关疾病中色氨酸代谢的分子解剖。

• 批准号: 23590362
• 负责人: FUNAKOSHI Hiroshi
• 金额: $ 3.41万
• 依托单位: Asahikawa Medical College
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2011
• 资助国家: 日本
• 起止时间: 2011 至 2013
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-23590362/
• 关键词: tryptophan; tryptophan dioxygenase; indoleamine dioxygenase; キヌレニン; 情動; 代謝; ノックアウトマウス; TDO; トリプトファン（Trp）; Tryptophan dioxygenase; Indoleamine dioxygenase; キヌレニン（KYN）; ノックアウトマウス（KOマウス）; Tryptophan; トリプトファン; セロトニン; トリプトファン2,3-ジオキシゲナーゼ; トリプト

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.

色氨酸 (Trp) 通过这些主要途径代谢；血清素能、转氨能和犬尿素能 (Kyn) 途径，Kyn 途径贡献了约 95% 的色氨酸代谢。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酶，这些酶的体内分析受到了限制。在这里，我们生成了 TDO-KO 小鼠，并阐明了 TDO 在以下方面的作用：（1）体循环和大脑中的色氨酸代谢（2）不同食物条件下的色氨酸代谢，包括 NAD（3）更高的脑功能和免疫功能以及（4）情绪疾病。

项目成果

Aryl hydrocarbon receptor control of a disease tolerance defense pathway

芳烃受体控制疾病耐受性防御途径

• 发表时间: 2014
• 期刊: Nature
• 影响因子: 64.8
• 作者: Puccetti P;Gargaro M;Pallotta M;Matino D;Vacca C;Volpi C;Belladonna M;Orabona C;Bianchi R;Grohmann U;Fallarino F;Iannitti R;Tissi L;Zelante T;Romani L;Servillo G;Brunacci C;Fazia MD;Piobbico D;Bessede A;Bicciato S;Mazza E;Macchiarulo
• 通讯作者: Macchiarulo

「こころ」の発達におけるトリプトファン代謝酵素Tryptophan 2,3-dioxygenase の生理的役割

色氨酸代谢酶色氨酸2,3-双加氧酶在心智发育中的生理作用

• DOI: 10.11266/jpan.14.suppl_69
• 发表时间: 2011
• 作者: 将昭 金井;敏一 中村;洋 船越
• 通讯作者: 洋 船越

Hepatocyte growth factor overexpression in the nervous system enhances learning and memory performance in mice

• DOI: 10.1002/jnr.23065
• 发表时间: 2012-09-01
• 期刊: JOURNAL OF NEUROSCIENCE RESEARCH
• 影响因子: 4.2
• 作者: Kato, Takashi;Funakoshi, Hiroshi;Nakamura, Toshikazu
• 通讯作者: Nakamura, Toshikazu

Hepatocyte growth factor (HGF) overexpression in the nervous system enhances learning and memory performance in mice

肝细胞生长因子（HGF）在神经系统中过度表达可增强小鼠的学习和记忆能力

• 发表时间: 2012
• 期刊: J. Neurosci. Res. (Corresponding authors)
• 作者: Kato T;Funakoshi H;Kadoyama K;Noma S;Kanai M;Ohya-Shimada W;Mizuno S;Doe N;Taniguchi T;Nakamura T
• 通讯作者: Nakamura T

Strong neurogenesis, angiogenesis and anti-fibrosis of hepatocyte growth factor in rats brain after transient middle cerebral artery occlusion (tMCAO)

短暂性大脑中动脉闭塞（tMCAO）后大鼠脑内肝细胞生长因子的强神经发生、血管生成和抗纤维化作用

• 发表时间: 2011
• 期刊: J Neurosci Res
• 影响因子: 4.2
• 作者: Shang J;Deguchi K;Ohta Y;Liu N;Zhang X;Tian F;Yamashita T;Ikeda Y;Matsuura T;Funakoshi H;Nakamura T;Abe K
• 通讯作者: Abe K