Developmental role of tryptophan hydroxylase in the nervous system

被引：53
作者：
Nakamura, Kazuhiro [1 ]
Hasegawa, Hiroyuki
机构：
[1] Juntendo Univ, Sch Med, Dept Pathol, Tokyo 113, Japan
[2] Teikyo Univ Sci & Technol, Dept Biosci, Yamanashi, Japan
来源：
MOLECULAR NEUROBIOLOGY | 2007年 / 35卷 / 01期
关键词：
brain function; development; serotonin; tryptophan hydroxylase 1; tryptophan hydroxylase 2;
D O I：
10.1007/BF02700623
中图分类号：
Q189 [神经科学];
学科分类号：
071006 ;
摘要：
The serotonin 5-hydroxytryptamine (5-HT) neurotransmitter system contributes to various physiological and pathological conditions. 5-HT is the first neurotransmitter for which a developmental role was suspected. Tryptophan hydroxylase (TPH) catalyzes the rate-limiting reaction in the biosynthesis of 5-HT. Both TPH1 and TPH2 have tryptophan hydroxylating activity TPH2 is abundant in the brain, whereas TPH1 is mainly expressed in the pineal gland and the periphery. However, TPH1. was found to be expressed predominantly during the late developmental stage in the brain. Recent advances have shed light on the kinetic properties of each TPH isoform. TPH1 showed greater affinity for tryptophan and stronger enzymic activity than TPH2 under conditions reflecting those in the developing brain stem. Transient alterations in 5-HT homeostasis during development modify the fine wiring of brain connections and cause permanent changes to adult behavior. An increasing body of evidence suggests the involvement of developmental brain disturbances in psychiatric disorders. These findings have revived a long-standing interest in the developmental role of 5-HT-related molecules. This article summarizes our understanding of the kinetics and possible neuronal functions of each TPH during development and in the adult.
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页码：45 / 53
页数：9
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