Sleep Research Centre, Faculty of Health and Medical Sciences, University of Surrey, Guildford GU2 7XP, UK.
GIGA-Research, Cyclotron Research Centre-In Vivo Imaging Unit, University of Liège, Belgium; Psychology and Neuroscience of Cognition Research Unit (PsyNCog), Faculty of Psychology and Educational Sciences, University of Liège, Belgium.
Sleep Med Rev. 2018 Aug;40:109-126. doi: 10.1016/j.smrv.2017.10.008. Epub 2017 Nov 6.
Period3 (Per3) is one of the most robustly rhythmic genes in humans and animals. It plays a significant role in temporal organisation in peripheral tissues. The effects of PER3 variants on many phenotypes have been investigated in targeted and genome-wide studies. PER3 variants, especially the human variable number tandem repeat (VNTR), associate with diurnal preference, mental disorders, non-visual responses to light, brain and cognitive responses to sleep loss/circadian misalignment. Introducing the VNTR into mice alters responses to sleep loss and expression of sleep homeostasis-related genes. Several studies were limited in size and some findings were not replicated. Nevertheless, the data indicate a significant contribution of PER3 to sleep and circadian phenotypes and diseases, which may be connected by common pathways. Thus, PER3-dependent altered light sensitivity could relate to high retinal PER3 expression and may contribute to altered brain response to light, diurnal preference and seasonal mood. Altered cognitive responses during sleep loss/circadian misalignment and changes to slow wave sleep may relate to changes in wake/activity-dependent patterns of hypothalamic gene expression involved in sleep homeostasis and neural network plasticity. Comprehensive characterisation of effects of clock gene variants may provide new insights into the role of circadian processes in health and disease.
PER3 是人类和动物中节律性最强的基因之一。它在周围组织的时间组织中起着重要作用。PER3 变体对许多表型的影响已在靶向和全基因组研究中进行了研究。PER3 变体，特别是人类可变数串联重复（VNTR），与昼夜偏好、精神障碍、非视觉对光的反应、大脑和认知对睡眠剥夺/昼夜节律失调的反应有关。将 VNTR 引入小鼠会改变对睡眠剥夺和与睡眠稳态相关基因表达的反应。一些研究规模有限，有些发现没有得到复制。尽管如此，这些数据表明 PER3 对睡眠和昼夜节律表型和疾病有重要贡献，这些表型和疾病可能通过共同的途径联系在一起。因此，PER3 依赖性的光敏感性改变可能与高视网膜 PER3 表达有关，并可能导致大脑对光的反应改变、昼夜偏好和季节性情绪改变。睡眠剥夺/昼夜节律失调期间认知反应改变和慢波睡眠改变可能与涉及睡眠稳态和神经网络可塑性的下丘脑基因表达的觉醒/活动依赖性模式改变有关。时钟基因变体影响的综合特征可能为昼夜节律过程在健康和疾病中的作用提供新的见解。
