Effect of Jian-Pi-Zhi-Dong Decoction on the Amino Acid Neurotransmitters in a Rat Model of Tourette Syndrome and Comorbid Anxiety Disorder.

Wen Zhang,Wenjing Yu,Sumei Wang,Xia Cui,Xiaofang Liu,Qian Wang,Xue Bai

doi:10.3389/fpsyt.2020.00515

Abstract

Amino acid neurotransmitters have been shown to correlate with Tourette syndrome (TS) and its comorbidities. In this study, we investigated the effects of Jian-Pi-Zhi-Dong Decoction (JPZDD), a formula containing 10 different Chinese medical herbs, on amino acid neurotransmitters in rats. We established a rat model of Tourette syndrome and comorbid anxiety with an iminodipropionitrile injection plus uncertain empty water bottle stimulation for 3 weeks. Then the rats were randomly divided into four groups: control group and model group were gavaged with saline, while the remaining two treatment groups were gavaged with fluoxetine hydrochloride or JPZDD for four consecutive weeks. We recorded the behaviors of the rats with TS and comorbid anxiety by stereotypy recording, open field test, and elevated plus maze. We observed mitochondrial changes with transmission electron microscopy. We measured the content of glutamate (GLU) and γ-aminobutyric acid (GABA) both in the serum and striatum and the expression of their receptors by Western blot and real-time polymerase chain reaction. The study revealed that JPZDD was effective in alleviating the behavioral symptoms of both tic and anxiety in the rat model groups. These results might be associated with the increase in GABA levels and decrease in GLU levels in the serum, as well as an increase in striatal GABA level by the activation of GABA receptors Type A (GABAAR). JPZDD treatment also reversed the mitochondrial dysfunction both in the striatum and cortex in affected animals.

Highlights

Tourette syndrome (TS) is a neuropsychiatric condition with the manifestation of multiple, spontaneous movements and vocalizations called tics
Our findings indicated that Jian-Pi-Zhi-Dong decoction (JPZDD) significantly reversed the anxiety behavior of TS and comorbid anxiety rats in the open field test (OFT) and elevated plus maze (EPM) tests
Comorbidity, or the presence of more than one disorder in an individual, is a prevalent condition affecting of the global population with TS

Summary

Introduction

Tourette syndrome (TS) is a neuropsychiatric condition with the manifestation of multiple, spontaneous movements and vocalizations called tics. TS is diagnosed by the onset of multiple motor tics and vocal tics lasting at least 1 year in clinic. The different tics do not need to present concurrently, but manifest at some point throughout the course of the illness [1]. The clinical impact of co-occurring conditions may be greater and compromise an extra burden much more than the tics [2]. Treatment of comorbidities is crucial for all patients with TS, but few studies have fully characterized these comorbidities. The purpose of this study was to determine if Chinese traditional medicine could affect neurotransmitters and mitochondrial function in model rats with TS and comorbid anxiety

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