RESUMEN
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.
Asunto(s)
Factores de Transcripción ARNTL/genética , Melatonina/administración & dosificación , Enfermedad de Parkinson/tratamiento farmacológico , Proteínas Circadianas Period/genética , Trastornos del Sueño-Vigilia/tratamiento farmacológico , Factores de Transcripción ARNTL/sangre , Adulto , Anciano , Estudios Cruzados , Método Doble Ciego , Femenino , Regulación de la Expresión Génica , Humanos , Masculino , México , Persona de Mediana Edad , Enfermedad de Parkinson/sangre , Enfermedad de Parkinson/diagnóstico , Enfermedad de Parkinson/genética , Proteínas Circadianas Period/sangre , Proyectos Piloto , Trastornos del Sueño-Vigilia/sangre , Trastornos del Sueño-Vigilia/diagnóstico , Trastornos del Sueño-Vigilia/genética , Factores de Tiempo , Resultado del TratamientoRESUMEN
It has been suggested that mitochondrial dysfunction and defects in membrane structure could be implied in AD pathogenesis. The aim of the present work was the study of membrane fluidity in submitochondrial platelet particles and erythrocyte membranes from Mexican patients. Blood samples were obtained from 30 patients with Alzheimer disease and 30 aged-matched control subjects. Membrane fluidity determinations were done using a very low concentration of the fluorescent dipyrenylpropane probe incorporated in both types of membranes. This probe is able to give excimer and monomer fluorescence, therefore it can be used to monitor fluidity changes in biological membranes. The data obtained showed that in submitochondrial particles from AD patients, the excimer to monomer fluorescent intensity ratio was lower (0.231 +/- 0.008) than aged-matched control subjects (0.363 +/- 0.014). Therefore, membrane fluidity was lower in AD samples. On the other hand, we found similar membrane fluidity in erythrocytes from AD patients and aged-matched controls: the fluorescent intensity ratios were 0.312 +/- 0.03 and 0.305 +/- 0.033, respectively. In addition, lipid peroxidation in submitochondrial particles and erythrocyte membranes was higher in AD samples than in aged-matched controls. These data suggest that submitochondrial platelet particles are more sensitive to oxidative stress than erythrocyte membranes.