Effect of melatonin administration on the PER1 and BMAL1 clock genes in patients with Parkinson's disease

D L Delgado-Lara; G V González-Enríquez; B M Torres-Mendoza; H González-Usigli; J Cárdenas-Bedoya; M A Macías-Islas; A Celis de la Rosa; A Jiménez-Delgado; F Pacheco-Moisés; J A Cruz-Serrano; G G Ortiz

doi:10.1016/j.biopha.2020.110485

Effect of melatonin administration on the PER1 and BMAL1 clock genes in patients with Parkinson's disease

Biomed Pharmacother. 2020 Sep:129:110485. doi: 10.1016/j.biopha.2020.110485. Epub 2020 Jul 6.

Affiliations

¹ Department of Philosophical and Methodological Disciplines, University Health Sciences Center, University of Guadalajara, Guadalajara, Jalisco, Mexico.
² Department of Philosophical and Methodological Disciplines, University Health Sciences Center, University of Guadalajara, Guadalajara, Jalisco, Mexico; Division of Neurosciences, Western Biomedical Research Center, Mexican Institute of Social Security, Guadalajara, Jalisco, Mexico.
³ Department of Neurology, Sub-Specialty Medical Unit, Western National Medical Center, Mexican Institute of Social Security, Guadalajara, Jalisco, Mexico.
⁴ Department of Neurosciences, University Health Sciences Center, University of Guadalajara, Guadalajara, Jalisco, Mexico.
⁵ Department of Public Health, University Health Sciences Center, University of Guadalajara, Guadalajara, Jalisco, Mexico.
⁶ Department of Chemistry, University Center of Exact Sciences and Engineering, University of Guadalajara, Guadalajara, Jalisco, Mexico.
⁷ Kurago Biotek, Guadalajara, Jalisco, Mexico.
⁸ Department of Philosophical and Methodological Disciplines, University Health Sciences Center, University of Guadalajara, Guadalajara, Jalisco, Mexico; Department of Neurology, Sub-Specialty Medical Unit, Western National Medical Center, Mexican Institute of Social Security, Guadalajara, Jalisco, Mexico. Electronic address: genarogabriel@yahoo.com.

PMID: 32768967
DOI: 10.1016/j.biopha.2020.110485

Abstract

Sleep disorders are a widespread condition in patients with Parkinson's disease (PD), which has been linked to a deregulation of the circadian cycle and therefore of the clock genes. The aim of this study was to evaluate the effect of melatonin (MEL) on the PER1 and BMAL1 clock genes in patients with PD. A double-blind, cross-over, placebo-controlled randomized clinical trial pilot study was conducted in 26 patients with stage 1-3 PD according to the Hoehn & Yahr scale, who received either 25 mg of MEL or a placebo at noon and 30 min before bedtime for three months. The relative expression of the PER1 and BMAL1 genes was measured, as well as the presence of daytime, nocturnal, and global sleepiness, and the progression of PD. The levels of the PER1 and BMAL1 genes at baseline were 0.9 (0.1-3) vs. 0.56 (0.1-2.5), respectively; while after the intervention with MEL or placebo the BMAL1 levels increased to 2.5 (0-3.70) vs. 2.2 (0.10-3.30), respectively (d = 0.387). Fifty percent (50 %) of patients had daytime sleepiness and sixty-five percent (65 %) had abnormal nighttime sleepiness, yet neither group showed changes after the intervention. Patients with PD exhibited an alteration in the levels of the clock genes: MEL increased the levels of BMAL1, but the PER1 levels remained unchanged.

Keywords: BMAL1gene; Clock genes; Melatonin; PER1gene; Parkinson's disease.

Publication types

Randomized Controlled Trial

MeSH terms

ARNTL Transcription Factors / blood
ARNTL Transcription Factors / genetics*
Adult
Aged
Cross-Over Studies
Double-Blind Method
Female
Gene Expression Regulation
Humans
Male
Melatonin / administration & dosage*
Mexico
Middle Aged
Parkinson Disease / blood
Parkinson Disease / diagnosis
Parkinson Disease / drug therapy*
Parkinson Disease / genetics
Period Circadian Proteins / blood
Period Circadian Proteins / genetics*
Pilot Projects
Sleep Wake Disorders / blood
Sleep Wake Disorders / diagnosis
Sleep Wake Disorders / drug therapy*
Sleep Wake Disorders / genetics
Time Factors
Treatment Outcome

Substances

ARNTL Transcription Factors
BMAL1 protein, human
PER1 protein, human
Period Circadian Proteins
Melatonin