Developmental role of tryptophan hydroxylase in the nervous system |
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Authors: | Kazuhiro Nakamura Hiroyuki Hasegawa |
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Institution: | (1) Department of Pathology, Juntendo University School of Medicine, Tokyo, Japan;(2) Department of Biosciences, Teikyo University of Science and Technology, Uenohara, Yamanashi, Japan |
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Abstract: | 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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Keywords: | Brain function development serotonin trypophan hydroxylase 1 tryptophan hydroxylase 2 |
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