PDF(Pubmed)
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.
摘要：
帕金森病（PD）的特点是一个长的前驱期，在此期间，患者经常有睡眠障碍。组胺能系统和昼夜节律在调节睡眠-觉醒周期中起重要作用。这些系统功能的变化可能与PD早期的发病机理有关，并且可能与年龄有关。这里,我们分析了与睡眠-觉醒周期调节相关的基因表达变化(Hnmt，Hrh1，Hrh3，Per1，Per2和Chrm3）在不同年龄的正常雄性小鼠的黑质（SN）和纹状体中，以及在MPTP诱导的PD早期症状期（ESS）模型的年轻和成年雄性小鼠中。正常小鼠脑组织中的年龄依赖性表达分析揭示了成年小鼠相对于年轻小鼠的Hrh3，Per1，Per2和Chrm3基因的变化。当用MPTP诱导的PDESS模型检测小鼠的基因表达时，仅在具有PDESS模型的成年小鼠的SN中发现了所有研究基因表达的变化。这些数据表明，年龄是影响PD发展中与睡眠-觉醒周期调节相关的基因表达变化的重要因素。
