ABSTRACT
Parkinson's disease (PD) is one of the most common human neurodegenerative diseases. Belated diagnoses of PD and late treatment are caused by its elongated prodromal phase. Thus, searching for new candidate genes participating in the development of the pathological process in the early stages of the disease in patients who have not yet received therapy is relevant. Changes in mRNA and protein levels have been described both in the peripheral blood and in the brain of patients with PD. Thus, analysis of changes in the mRNA expression in peripheral blood is of great importance in studying the early stages of PD. This work aimed to analyze the changes in MEF2C, SLC22A4, P2RY12, and LRRN3 gene expression in the peripheral blood of patients in the early stages of PD. We found a statistically relevant and PD-specific change in the expression of the LRRN3 gene, indicating a disruption in the processes of neuronal regeneration and the functioning of synapses. The data obtained during the study indicate that this gene can be considered a potential biomarker of the early stages of PD.
ABSTRACT
Parkinson's disease (PD) is characterized by a long prodromal period, during which patients often have sleep disturbances. The histaminergic system and circadian rhythms play an important role in the regulation of the sleep-wake cycle. Changes in the functioning of these systems may be involved in the pathogenesis of early stages of PD and may be age-dependent. Here, we have analyzed changes in the expression of genes associated with the regulation of the sleep-wake cycle (Hnmt, Hrh1, Hrh3, Per1, Per2, and Chrm3) in the substantia nigra (SN) and striatum of normal male mice of different ages, as well as in young and adult male mice with an MPTP-induced model of the early symptomatic stage (ESS) of PD. Age-dependent expression analysis in normal mouse brain tissue revealed changes in Hrh3, Per1, Per2, and Chrm3 genes in adult mice relative to young mice. When gene expression was examined in mice with the MPTP-induced model of the ESS of PD, changes in the expression of all studied genes were found only in the SN of adult mice with the ESS model of PD. These data suggest that age is a significant factor influencing changes in the expression of genes associated with sleep-wake cycle regulation in the development of PD.
Subject(s)
Circadian Rhythm , Animals , Mice , Male , Circadian Rhythm/genetics , Gene Expression Regulation , Mice, Inbred C57BL , Sleep/genetics , Aging/genetics , Disease Models, Animal , Parkinson Disease/genetics , Parkinson Disease/metabolism , Substantia Nigra/metabolism , Corpus Striatum/metabolism , MPTP Poisoning/genetics , MPTP Poisoning/metabolism , Age Factors , 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine , WakefulnessABSTRACT
Parkinson's disease (PD) is a common chronic, age-related neurodegenerative disease. This disease is characterized by a long prodromal period. In this context, it is important to search for the genes and mechanisms that are involved in the development of the pathological process in the earliest stages of the disease. Published data suggest that blood cells, particularly lymphocytes, may be a model for studying the processes that occur in the brain in PD. Thus, in the present work, we performed an analysis of changes in the expression of the genes ADORA2A, MTA1, PTGDS, PTGS2, NSF, and HNMT in the peripheral blood of patients with early stages of PD (stages 1 and 2 of the Hoehn-Yahr scale). We found significant and PD-specific expression changes of four genes, i.e., MTA1, PTGS2, NSF, and HNMT, in the peripheral blood of patients with early stages of PD. These genes may be associated with PD pathogenesis in the early clinical stages and can be considered as potential candidate genes for this disease. Altered expression of the ADORA2A gene in treated PD patients may indicate that this gene is involved in processes affected by antiparkinsonian therapy.
Subject(s)
Neurodegenerative Diseases , Parkinson Disease , Humans , Parkinson Disease/drug therapy , Cyclooxygenase 2/genetics , Neurodegenerative Diseases/complications , Brain/pathology , Gene ExpressionABSTRACT
Parkinson's disease (PD) is one of the most common neurodegenerative diseases. Investigating individuals with the most identical genetic background is optimal for minimizing the genetic contribution to gene expression. These individuals include monozygotic twins discordant for PD. Monozygotic twins have the same genetic background, age, sex, and often similar environmental conditions. The aim of this study was to carry out a transcriptome analysis of the peripheral blood of three pairs of monozygotic twins discordant for PD. We identified the metabolic process "circadian behavior" as a priority process for further study. Different expression of genes included in the term "circadian behavior" confirms that this process is involved in PD pathogenesis. We found increased expression of three genes associated with circadian behavior, i.e., PTGDS, ADORA2A, and MTA1, in twins with PD. These genes can be considered as potential candidate genes for this disease.