PTPRD as a candidate druggable target for therapies for restless legs syndrome?. (27th October 2020)

• Record Type: Journal Article
• Authors: Morais, Milca A.; Franco, Beatriz; Holanda, Alessandro S. S.; Simino, Laís Angélica de Paula; Manconi, Mauro; Torsoni, Adriana; Esteves, Andrea M.
• Is Part Of: Journal of sleep research. Volume 30:Number 4(2021)
• Page Start: n/a
• Page End: n/a
• Publication Date: 2020-10-27
• Subjects: dopaminergic agonist -- dopaminergic neurons -- drugged -- polysomnography -- sensorimotor disorder; Sleep -- Periodicals; Sleep disorders -- Periodicals; 612.821
• DOI: 10.1111/jsr.13216
• Languages: English
• ISSNs: 0962-1105

Abstract

Abstract: The gene that encodes the protein tyrosine phosphatase D (PTPRD) may be related to brain circuits associated with sleep, and has been seen as an interesting molecule, a "druggable" drug target. This gene is a potential candidate for increasing therapeutic advances in restless legs syndrome, a sleep‐related movement disorder, that manifests as an uncontrollable desire to move limbs (legs) to relieve uncomfortable sensations. Changes in the PTPRD gene expression may increase the chance of developing this syndrome. Treatment with pramipexole is used in restless legs syndrome. This study aims to verify the effect of treatment with pramipexole on the PTPRD expression, as well as on the sleep pattern in an animal model for restless legs syndrome. For this, an animal model of sleep‐related movement disorders (spontaneously hypertensive rats) was distributed in groups: (a) spontaneously hypertensive rats−control; (b) spontaneously hypertensive rats−pramipexole (0.125 mg kg −1 for 4 weeks). The analyses of PTPRD gene and protein expression were performed in the striatum and spinal cord by quantitative real‐time polymerase chain reaction and indirect enzyme‐linked immunosorbent assay, respectively. Electrocorticographic and electromyographic analyses were performed. There was no difference in the PTPRD mRNA levels, as well as in the protein levels, although a tendency has been observed for decreased gene expression in the striatum and increased protein expression in the spinal cord in the spontaneously hypertensive rats−pramipexole group. Pramipexole improved the animals' sleep pattern. Thus, the treatment with pramipexole in the evaluated dose and time tended to alter the expression of the PTPRD protein in the spinal cord, in addition to significantly improving the sleep pattern.