Lack of Tryptophan Hydroxylase-1 in Mice Results in Gait Abnormalities

Georgette L Suidan,Thomas G Hampton,Siu Ling Wong,Veronique Vanderhorst,Daniel Duerschmied,Jaymie R Voorhees,Denisa D Wagner,Gregory M Dillon,Toshiyuki Miyata

doi:10.1371/journal.pone.0059032

Abstract

The role of peripheral serotonin in nervous system development is poorly understood. Tryptophan hydroxylase-1 (TPH1) is expressed by non-neuronal cells including enterochromaffin cells of the gut, mast cells and the pineal gland and is the rate-limiting enzyme involved in the biosynthesis of peripheral serotonin. Serotonin released into circulation is taken up by platelets via the serotonin transporter and stored in dense granules. It has been previously reported that mouse embryos removed from Tph1-deficient mothers present abnormal nervous system morphology. The goal of this study was to assess whether Tph1-deficiency results in behavioral abnormalities. We did not find any differences between Tph1-deficient and wild-type mice in general motor behavior as tested by rotarod, grip-strength test, open field and beam walk. However, here we report that Tph1 (−/−) mice display altered gait dynamics and deficits in rearing behavior compared to wild-type (WT) suggesting that tryptophan hydroxylase-1 expression has an impact on the nervous system.

Highlights

Tryptophan hydroxylase (TPH) is the rate-limiting enzyme involved in the biosynthesis of serotonin [1,2]
We show that Tph1 (2/2) mice born from knockout mothers have altered gait dynamics throughout life and deficits in rearing behavior with age when compared to age-matched wild-type mice
Gait dynamics are altered in Tph1 (2/2) mice Gait dynamics in Tph1 (2/2) mice were significantly different when compared to age-matched controls

Summary

Introduction

Tryptophan hydroxylase (TPH) is the rate-limiting enzyme involved in the biosynthesis of serotonin [1,2]. Under normal conditions,TPH1 is predominantly expressed in a wide variety of non-neuronal cells such as enterochromaffin cells of the gut, mast cells and the pineal gland [3,4,5]. TPH2 is expressed in neurons of the central, peripheral and enteric nervous systems [3,4,5]. There appears to be no substantial overlap in the expression of the two TPH isoforms [6,7]. There is evidence that TPH1 mRNA is present in the raphenuclei during postnatal development where it may have an impact on the nervous system [8]

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