Globus Pallidus Internus Electric High-Frequency Stimulation Modulates Dopaminergic Activity in the Striatum of a Rat Model of Tourette Syndrome

World Neurosurg. 2019 Jul:127:e881-e887. doi: 10.1016/j.wneu.2019.03.290. Epub 2019 Apr 6.

Abstract

Objective: The purpose of this study was to investigate the role of deep brain stimulation (DBS) of the globus pallidus internus (GPi) in dopamine and dopamine transporter metabolism and to explore the regulatory role of DBS on dopaminergic neurons in Tourette syndrome by constructing an autoimmune model.

Methods: Serum with high concentrations of antinuclear antibodies or phosphate-buffered saline solution was injected into the striatum of rats by a stereotactic technique and micropump. Then, electrodes were planted in the rats' globus pallidus internus. Concentrations of dopamine and dopamine transporter in the striatum were detected by enzyme-linked immunosorbent assay, immunohistochemistry, and Western blot analysis after 7 days of high-frequency stimulation (130 Hz).

Results: The tic behavior score of rats in the Tourette syndrome group was higher than that of rats in the control group (P < 0.01). After high-frequency stimulation, the scores of the Tourette syndrome model group and the control group significantly decreased. The concentration of dopamine in the Tourette syndrome model group and the control group also significantly decreased after electric stimulation (P < 0.05). In addition, immunohistochemical analysis and Western blot test results showed that dopamine transporter in the Tourette syndrome model nonstimulation group was lower than in the Tourette syndrome model stimulation group, and that dopamine transporter in the control nonstimulation group was lower than in the control stimulation group (P < 0.05).

Conclusions: The results of this study show that the mechanism of DBS of the GPi in the treatment of Tourette syndrome involved monoamine neurotransmitters, especially the dopamine system, that affected the metabolism and transport of corresponding neurotransmitters, playing an important role in regulating the concentration of synaptic neurotransmitters and changing the biologic activity of basal ganglia nerve circuits.

Keywords: Deep brain stimulation; Dopamine; Dopamine transporter; Tourette syndrome.

MeSH terms

  • Animals
  • Corpus Striatum / physiopathology
  • Corpus Striatum / surgery
  • Deep Brain Stimulation* / methods
  • Disease Models, Animal
  • Dopamine Plasma Membrane Transport Proteins / metabolism
  • Electric Stimulation*
  • Globus Pallidus / physiopathology*
  • Globus Pallidus / surgery
  • Male
  • Neostriatum / physiopathology
  • Neostriatum / surgery
  • Rats, Sprague-Dawley
  • Tourette Syndrome / physiopathology*
  • Tourette Syndrome / surgery*
  • Treatment Outcome

Substances

  • Dopamine Plasma Membrane Transport Proteins