National Research Centre "Kurchatov Institute", 2 Kurchatova Sq., 123182 Moscow, Russia.
Scientific Center for Biomedical Technologies of the Federal Biomedical Agency of Russia, 119435 Krasnogorsk, Russia.
Int J Mol Sci. 2024 Jul 14;25(14):7721. doi: 10.3390/ijms25147721.
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 (, , , , , and ) 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 , , , and 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.
帕金森病(PD)的特征是存在很长的前驱期,在此期间患者常常出现睡眠障碍。组胺能系统和昼夜节律对睡眠-觉醒周期的调节起着重要作用。这些系统功能的变化可能与 PD 早期阶段的发病机制有关,并且可能与年龄有关。在这里,我们分析了与睡眠-觉醒周期调节相关的基因(、、、、、和)在不同年龄正常雄性小鼠的黑质(SN)和纹状体中的表达变化,以及在具有 MPTP 诱导的早期症状期(ESS)PD 模型的年轻和成年雄性小鼠中的表达变化。在正常小鼠脑组织中的年龄依赖性表达分析显示,成年小鼠相对于年轻小鼠,基因、、和表达发生了变化。当在具有 MPTP 诱导的 ESS 模型的 PD 小鼠中检查基因表达时,在具有 ESS 模型的 PD 成年小鼠的 SN 中仅发现所有研究基因的表达发生了变化。这些数据表明,年龄是影响 PD 发展过程中与睡眠-觉醒周期调节相关的基因表达变化的重要因素。