Spatio-temporal expression of tryptophan hydroxylase isoforms in murine and human brain: Convergent data from Tph2 knockout mice
Spatio-temporal expression of tryptophan hydroxylase isoforms in murine and human brain: Convergent data from Tph2 knockout mice
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DOI：
10.1016/j.euroneuro.2008.12.005
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发表时间：
2009-04-01
影响因子：
5.6
通讯作者：
Lesch, Klaus-Peter
中科院分区：
文献类型：
--
作者：
Gutknecht, Lise;Kriegebaum, Claudia;Lesch, Klaus-Peter
色氨酸羟化酶（TPH）依赖的5-羟色胺（5-HT）合成的失调，已被牵连在各种神经精神疾病，虽然这两种异构体的差异表达模式是有争议的。在这里，我们报告了一个全面的时空异构体特异性分析TPH 1和TPH 2的表达在出生前和出生后的小鼠大脑和成人大脑的发展。TPH 2的表达一致检测中缝核，以及在纤维中的深松果体和小肠。虽然在这些外周组织中发现了TPH 1表达，但在小鼠发育期间以及小鼠和成人大脑中均未检测到TPH 1表达。在支持TPH 2特异性脑5-HT合成，Tph 2基因敲除小鼠的中缝神经元完全缺乏5-HT，没有Tph 1表达的代偿性激活。总之，我们的研究结果表明，整个生命周期的大脑5-HT合成完全由TPH 2维持。(c)2008 Elsevier B.V.和ECNP。All rights reserved.
Dysregulation of tryptophan hydroxylase (TPH)-dependent serotonin (5-HT) synthesis, has been implicated in various neuropsychiatric disorders, although the differential expression pattern of the two isoforms is controversial. Here, we report a comprehensive spatio-temporal isoform-specific analysis of TPH1 and TPH2 expression during pre- and postnatal development of mouse brain and in adult human brain. TPH2 expression was consistently detected in the raphe nuclei, as well as in fibers in the deep pineal gland and in small intestine. Although TPH1 expression was found in these peripheral tissues, no significant TPH1 expression was detected in the brain, neither during murine development, nor in mouse and human adult brain. In support of TPH2 specificity in brain 5-HT synthesis, raphe neurons of Tph2 knockout mice were completely devoid of 5-HT, with no compensatory activation of Tph1 expression. In conclusion, our findings indicate that brain 5-HT synthesis across the lifespan is exclusively maintained by TPH2. (c) 2008 Elsevier B.V. and ECNP. All rights reserved.