Glial and tissue-specific regulation of Kynurenine Pathway dioxygenases by acute stress of mice.
Glial and tissue-specific regulation of Kynurenine Pathway dioxygenases by acute stress of mice.
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DOI：
10.1016/j.ynstr.2017.02.002
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发表时间：
2017-12
影响因子：
5
通讯作者：
McCusker RH
中科院分区：
文献类型：
--
作者：
Dostal CR;Carson Sulzer M;Kelley KW;Freund GG;McCusker RH
压力源激活下丘脑-垂体-肾上腺（HPA）轴和免疫系统，引起认知功能、情绪和焦虑的变化。应激和行为改变之间的一个重要联系是刺激犬尿氨酸途径，该途径产生神经活性和免疫调节犬尿氨酸。色氨酸进入该途径是由限速的吲哚胺/色氨酸2,3-双加氧酶（DOs: Ido1, Ido2, Tdo2）控制的。虽然涉及调解行为的变化，检测应激诱导DO表达已被证明是不一致的。因此，我们使用C57BL/6J小鼠来表征脑区、星形胶质细胞和小胶质细胞中的DO表达，以表征抑制应激诱导的DO表达。应激增加了脑和血浆中的犬尿氨酸，表明DO活性增加。在三种Ido1转录本中，只有Ido1-v1的表达在应激和星形胶质细胞中增加，而在小胶质细胞中没有，这表明转录本和胶质特异性。应激仅在额叶皮质和下丘脑中增加ido -v1，表明脑区域特异性。在8种Ido2转录本中，应激增加了Ido2-v3的表达，同样仅在星形胶质细胞内。同样，应激增加了星形胶质细胞中Tdo2-FL的表达，而不是小胶质细胞。有趣的是，Ido2和Tdo2转录本在Ido1敲除（Ido1KO）小鼠中没有相应的诱导，这表明Ido1对于急性应激的中枢DO反应是必要的。与导致小胶质细胞内DO诱导的急性炎症模型不同，只有星形胶质细胞DO表达在急性抑制应激下增加，这确定了它们在犬尿氨酸通路的应激依赖性激活中的独特作用。急性应激增加色氨酸向犬尿氨酸的代谢。应激增加星形胶质细胞Ido1、Ido2和Tdo2的表达。应激不增加Ido1KO小鼠星形胶质细胞中的Ido2。应激并没有增加mido1ko小鼠大脑中的Tdo2。应激对脑和肝的Ido1、Ido2和Tdo2的调节存在差异。
Stressors activate the hypothalamic-pituitary-adrenal (HPA) axis and immune system eliciting changes in cognitive function, mood and anxiety. An important link between stress and altered behavior is stimulation of the Kynurenine Pathway which generates neuroactive and immunomodulatory kynurenines. Tryptophan entry into this pathway is controlled by rate-limiting indoleamine/tryptophan 2,3-dioxygenases (DOs: Ido1, Ido2, Tdo2). Although implicated as mediating changes in behavior, detecting stress-induced DO expression has proven inconsistent. Thus, C57BL/6J mice were used to characterize DO expression in brain-regions, astrocytes and microglia to characterize restraint-stress-induced DO expression. Stress increased kynurenine in brain and plasma, demonstrating increased DO activity. Of three Ido1 transcripts, only Ido1-v1 expression was increased by stress and within astrocytes, not microglia, indicating transcript- and glial-specificity. Stress increased Ido1-v1 only in frontal cortex and hypothalamus, indicating brain-region specificity. Of eight Ido2 transcripts, Ido2-v3 expression was increased by stress, again only within astrocytes. Likewise, stress increased Tdo2-FL expression in astrocytes, not microglia. Interestingly, Ido2 and Tdo2 transcripts were not correspondingly induced in Ido1-knockout (Ido1KO) mice, suggesting that Ido1 is necessary for the central DO response to acute stress. Unlike acute inflammatory models resulting in DO induction within microglia, only astrocyte DO expression was increased by acute restraint-stress, defining their unique role during stress-dependent activation of the Kynurenine Pathway. Acute stress increased tryptophan metabolism to kynurenine. Stress increased Ido1, Ido2 and Tdo2 expression by astrocytes. Stress did not increase Ido2 in astrocytes from Ido1KO mice. Stress did not increase Tdo2 in brains fromIdo1KO mice. Brain and hepatic Ido1, Ido2 and Tdo2 are differentially regulated by stress.
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影响因子：
3.3
作者：
Browne, C. A.;O'Brien, F. E.;Cryan, J. F.
通讯作者：
Cryan, J. F.
影响因子：
3.3
作者：
Gabbay, Vilma;Ely, Benjamin A.;Liebes, Leonard
通讯作者：
Liebes, Leonard
影响因子：
10.6
作者：
Erhardt, S;Schwieler, L;Geyer, M
通讯作者：
Geyer, M
影响因子：
7.3
作者：
Brooks AK;Lawson MA;Rytych JL;Yu KC;Janda TM;Steelman AJ;McCusker RH
通讯作者：
McCusker RH
影响因子：
2.7
作者：
Fujigaki, Hidetsugu;Saito, Kuniaki;Seishima, Mitsuru
通讯作者：
Seishima, Mitsuru