Effectiveness of exercise and pramipexole in the treatment of restless leg syndrome: Implications on the dopaminergic system and PTPRD

Objective: Dopaminergic dysfunction, iron reduction and variations in the PTPRD gene (protein tyrosine phosphatase receptor type delta) may be associated with restless leg syndrome (RLS). Here, we evaluate the effect of pramipexole (PPX) and exercise on genes and proteins associated with RLS and on sleep patterns in spontaneously hypertensive rats (SHR). Methods: Animals were distributed into 4 groups: 1) Control (CTRL); 2) Exercise (EX); 3) Exercise and pramipexole (EX + PPX); and 4) Pramipexole (PPX). PPX treatment was performed daily (0.125 mg/kg), while exercise was conducted over 5 sessions per week, both for 4 weeks. Results: EX + PPX increased the protein levels of PTPRD, reduced the protein levels of the enzyme tyrosine hydroxylase (TH) and improved sleep parameters in both cycles; on the other hand, the use of PPX reduced mRNA and protein levels of PTPRD and TH but improved the sleep pattern in the light cycle. However, in the dark cycle, pramipexole caused the worsening of symptoms. Conclusions: We suggest that the improvement in sleep pattern by EX + PPX may be associated with the increased protein levels of PTPRD and that EX + PPX can reverse the negative effects of PPX.

Automated summary

This study investigated the effects of pramipexole (PPX) and exercise on genes and proteins associated with restless leg syndrome (RLS) and sleep patterns. The findings suggest that the combined use of exercise and PPX can increase PTPRD protein levels, decrease tyrosine hydroxylase (TH) protein levels, and improve sleep parameters. However, the use of PPX alone has negative effects on PTPRD and TH mRNA and protein levels, but can improve sleep patterns in the light cycle. In the dark cycle, PPX use worsens symptoms.