Protein tyrosine phosphatase receptor type delta (PTPRD) gene in an animal model of restless legs syndrome

J Sleep Res. 2023 Apr;32(2):e13716. doi: 10.1111/jsr.13716. Epub 2022 Sep 2.

Abstract

The pathophysiology of the restless legs syndrome (RLS) is related to dopaminergic dysfunction, reduced iron and variations in gene expression, such as the protein tyrosine phosphatase receptor type delta gene (PTPRD). Animal models could be key to achieving a mechanistic understanding of RLS and to facilitate efficient platforms for evaluating new therapeutics. Thus, the aim of this study was to evaluate the expression of PTPRD, of genes and proteins associated with RLS, the sleep patterns and the cardiovascular parameters in an animal model of RLS (spontaneously hypertensive rat [SHR]). Rats were divided into two groups: (i) Wistar-Kyoto and (ii) SHR. Cardiovascular parameters were assessed by tail plethysmography. Polysomnography was used to analyse the sleep pattern (24 h). For the PTPRD analyses, quantitative polymerase chain reaction (qPCR) and indirect enzyme-linked immunosorbent assay (ELISA) techniques were used. To evaluate the tyrosine hydroxylase enzyme, dopamine transporter (DAT) and type 2 dopaminergic receptor, qPCR and Western Blotting techniques were used. For the quantification of iron, ferritin and transferrin, the ELISA method was used. SHRs had higher blood pressure, alterations in sleep pattern, lower expression of protein content of PTPRD, lower expression of DAT, and lower serum concentrations of ferritin. These data suggest that the behavioural, physiological, and molecular changes observed in SHRs provide a useful animal model of RLS, reinforcing the importance of this strain as an animal model of this sleep disorder.

Keywords: cardiovascular diseases; polysomnography; single-nucleotide polymorphism; sleep-related movement disorder.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Dopamine
  • Ferritins
  • Iron
  • Models, Animal
  • Protein Tyrosine Phosphatases
  • Rats
  • Rats, Inbred SHR
  • Rats, Inbred WKY
  • Restless Legs Syndrome* / genetics

Substances

  • Iron
  • Dopamine
  • Ferritins
  • Protein Tyrosine Phosphatases