Jian-Pi-Zhi-Dong-Decoction regulates the expression of glutamate transporters to attenuate glutamate excitotoxicity and exerts anti-tics effects in Tourette syndrome model rats

Abstract

Purpose

This study explored whether Jian-Pi-Zhi-Dong-Decoction (JPZDD) could regulate the metabolism of glutamate (GLU) and its transporters in the striatum to exert anti-tics effects in Tourette syndrome (TS) rats.

Materials and methods

We randomly assigned 56 Sprague Dawley rats into four groups, each with 14 rats: control, model, tiapride (Tia), and JPZDD. TS groups (model, Tia, and JPZDD) received intraperitoneal injection of 3,3′-iminodipropionitrile for 7 days to establish TS model. Thereafter, rats in the four groups were treated differently once a day for 6 weeks. Behavioral evaluation was performed each week by using stereotypy recording and autonomic activity test. The level of GLU in the striatum was examined by high-performance liquid chromatography. Expression of EAAT1 and VGLUT1 were measured by quantitative real-time PCR (qRT-PCR) and laser scanning confocal microscope.

Results

Compared with the model group, the stereotypy score and autonomic activity were decreased in Tia and JPZDD groups. Notably, the model group had increased concentration of GLU, which decreased after JPZDD and Tia treatments. In the model group, EAAT1 and glial cells were highly co-expressed and the relative fluorescence intensity (FI) of EAAT1 was significantly lower than that in the control group. Treatment with JPZDD and Tia increased the relative FI of EAAT1. The mRNA level of EAAT1 decreased in the model group compared to that in the control group, although it was significantly elevated following JPZDD or Tia treatment. In the model group, there was low co-expression of VGLUT1 and axon cells and the FI of VGLUT1 was remarkably increased relative to that in the control group and reduced following treatment with JPZDD and Tia. A similar trend was observed in the mRNA and protein expression of VGLUT1, although it was not statistically significant.

Conclusion

The mechanism by which JPZDD alleviated behavioral dysfunction of TS rats may be associated with maintaining normal GLU transport by upregulating EAAT1 and down-regulating VGLUT1 in the striatum.

Keywords:

• Jian-Pi-Zhi-Dong-Decoction
• Tourette syndrome
• glutamate
• EAAT1
• VGLUT1

Acknowledgments

This work was funded by grants from National Natural Science Foundation of China (No 81273799) and Beijing Natural Science Foundation (No 7182101).

Author contributions

Wenjing Yu and Xiaowei Shi performed the experiment, data analyses, and graphics production and wrote the manuscript. Xia Cui, Yan Niu, Wen Zhang, Xue Bai, Qian Wang, and Lijun Hu helped to perform the experiment and data analyses. Sumei Wang conceived and designed the experiment, provided finance and technology support, and guided and revised the manuscript. All authors contributed to data analysis, drafting or revising the article, gave final approval of the version to be published, and agree to be accountable for all aspects of the work.

Disclosure

The authors report no conflicts of interest in this work.