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Author Notes:

Correspondence: Xuebing Cao caoxuebing@126.com

CZ and GC contributed equally to this work.

CZ, GC, YX, ZZ, SP, KY, and XC conceived and designed the study.

CZ, GC, YT, WZ, QP, JW, CC, XY, and SN performed the experiments.

CZ and GC analyzed the data.

CZ, GC, YX, SP, KY, and XC wrote the manuscript.

All authors read and approved the final manuscript.

We would like to thank Pro. Jiangeng Huang from Department of Pharmaceutics, School of Pharmacy, Tongji Medical College, Huazhong University of Science and Technology for kindly providing microdialysis devices and technical guidance.

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

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Research Funding:

This work was supported by the National Natural Science Foundation of China (81171193, 81671108, and 81873734) and Natural Science Foundation of Hubei Province of China (2016CFB544).

Keywords:

  • Science & Technology
  • Life Sciences & Biomedicine
  • Neurosciences
  • Neurosciences & Neurology
  • Parkinson's disease
  • TRH
  • Taltirelin
  • L-DOPA
  • dopamine
  • tyrosine hydroxylase
  • THYROTROPIN-RELEASING-HORMONE
  • TYROSINE-HYDROXYLASE GENE
  • PARKINSONS-DISEASE
  • NUCLEUS-ACCUMBENS
  • EXTRACELLULAR DOPAMINE
  • IN-VIVO
  • PROJECTION NEURONS
  • STRIATAL NEURONS
  • CHRONIC LEVODOPA
  • BASAL GANGLIA

TRH Analog, Taltirelin Improves Motor Function of Hemi-PD Rats Without Inducing Dyskinesia via Sustained Dopamine Stimulating Effect

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Journal Title:

Frontiers in Cellular Neuroscience

Volume:

Volume 12

Publisher:

, Pages 417-417

Type of Work:

Article | Final Publisher PDF

Abstract:

Thyrotropin-releasing hormone (TRH) and its analogs are able to stimulate the release of the endogenic dopamine (DA) in the central nervous system. However, this effect has not been tested in the Parkinson’s disease (PD), which is characterized by the DA deficiency due to the dopaminergic neurons loss in the substantia nigra. Here, we investigated the therapeutic effect of Taltirelin, a long-acting TRH analog on 6-hydroxydopamine-lesioned hemi-Parkinsonian rat model. 1–10 mg/kg Taltirelin i.p. administration significantly improved the locomotor function and halted the electrophysiological abnormities of PD animals without inducing dyskinesia even with high-dose for 7 days treatment. Microdialysis showed that Taltirelin gently and persistently promoted DA release in the cortex and striatum, while L-DOPA induced a sharp rise of DA especially in the cortex. The DA-releasing effect of Taltirelin was alleviated by reserpine, vanoxerine (GBR12909) or AMPT, indicating a mechanism involving vesicular monoamine transporter-2 (VMAT-2), dopamine transporter (DAT) and tyrosine hydroxylase (TH). The in vivo and in vitro experiments further supported that Taltirelin affected the regulation of TH expression in striatal neurons, which was mediated by p-ERK1/2. Together, this study demonstrated that Taltirelin improved motor function of hemi-PD rats without inducing dyskinesia, thus supporting a further exploration of Taltirelin for PD treatment.

Copyright information:

© 2018 Zheng, Chen, Tan, Zeng, Peng, Wang, Cheng, Yang, Nie, Xu, Zhang, Papa, Ye and Cao.

This is an Open Access work distributed under the terms of the Creative Commons Attribution 4.0 International License (https://creativecommons.org/licenses/by/4.0/).
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