Tryptophan 2,3-dioxygenase is a key modulator of physiological neurogenesis and anxiety-related behavior in mice.
Tryptophan 2,3-dioxygenase is a key modulator of physiological neurogenesis and anxiety-related behavior in mice.
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DOI：
10.1186/1756-6606-2-8
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发表时间：
2009-03-27
期刊：
影响因子：
3.6
通讯作者：
Nakamura T
中科院分区：
文献类型：
--
作者：
Kanai M;Funakoshi H;Takahashi H;Hayakawa T;Mizuno S;Matsumoto K;Nakamura T
虽然营养素，包括氨基酸及其代谢产物，如5-羟色胺（5-HT），是焦虑相关行为的强调节剂，但负责这种生理调节的代谢途径尚未完全了解。关于色氨酸（Trp），色氨酸代谢的犬尿氨酸途径的初始限速酶是色氨酸2，3-双加氧酶（TDO）和吲哚胺2，3-双加氧酶（IDO）。在这里，我们产生了tdo缺陷的小鼠（Tdo-/-）。与野生型同窝出生小鼠相比，Tdo-/-小鼠显示Trp及其代谢物5-羟基吲哚乙酸（5-HIAA）和犬尿氨酸的血浆水平增加，以及海马和中脑中Trp、5-HT和5-HIAA的水平增加。这些小鼠在高架十字迷宫和旷场试验中也显示出抗焦虑调节，并增加成年神经发生，如BrdU和神经祖细胞/神经元标记物的双重染色所证明的。这些发现表明，在生理条件下，色氨酸代谢和神经发生以及焦虑相关行为之间存在直接的分子联系。
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.
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影响因子：
10.6
作者：
Lucki, I
通讯作者：
Lucki, I
DOI：
10.1016/j.bbagen.2005.03.010
发表时间：
2005-06-20
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