Netherlands Institute for Neuroscience, an Institute of the Royal Netherlands Academy of Arts and Sciences, Amsterdam, The Netherlands; Departments of Integrative Neurophysiology and Psychiatry, Center for Neurogenomics and Cognitive Research, Neuroscience Campus Amsterdam, VU University and Medical Center, Amsterdam, The Netherlands.
Donders Centre for Cognition and Donders Institute for Brain, Cognition and Behaviour, Radboud University, Nijmegen, The Netherlands.
Neurobiol Learn Mem. 2019 Apr;160:132-138. doi: 10.1016/j.nlm.2018.05.017. Epub 2018 Jun 1.
Atrophy of the medial temporal lobe of the brain is key to memory function and memory complaints in old age. While age and some morbidities are major risk factors for medial temporal lobe atrophy, individual differences remain, and mechanisms are insufficiently known. The largest combined neuroimaging and whole genome study to date indicates that medial temporal lobe volume is most associated with common polymorphisms in the GRIN2B gene that encodes for the 2B subunit (NR2B) of the NMDA receptor. Because sleep disruption induces a selective loss of NR2B from hippocampal synaptic membranes in rodents, and because of several other reports on medial temporal lobe sensitivity to sleep disruption, we hypothesized a contribution of the typical age-related increase in sleep-wake rhythm fragmentation to medial temporal lobe atrophy. Magnetic resonance imaging and actigraphy in 138 aged individuals showed that individual differences in sleep-wake rhythm fragmentation accounted for more (19%) of the variance in medial temporal lobe atrophy than age did (15%), or any of a list of health and brain structural indicators. The findings suggest a role of sleep-wake rhythm fragmentation in age-related medial temporal lobe atrophy, that might in part be prevented or reversible.
大脑内侧颞叶萎缩是老年记忆功能和记忆障碍的关键。虽然年龄和一些疾病是内侧颞叶萎缩的主要危险因素，但个体差异仍然存在，而且机制还不够清楚。迄今为止最大的联合神经影像学和全基因组研究表明，内侧颞叶体积与 NMDA 受体 2B 亚单位（NR2B）编码基因 GRIN2B 中的常见多态性最相关。由于睡眠中断会导致啮齿动物海马突触膜中 NR2B 的选择性丢失，而且由于其他一些关于内侧颞叶对睡眠中断敏感性的报告，我们假设典型的与年龄相关的睡眠-觉醒节律碎片化增加会导致内侧颞叶萎缩。对 138 名老年人的磁共振成像和活动记录仪检查显示，睡眠-觉醒节律碎片化的个体差异在内侧颞叶萎缩的变异中占比（19%）高于年龄（15%），也高于健康和大脑结构指标列表中的任何一项。这些发现表明睡眠-觉醒节律碎片化在与年龄相关的内侧颞叶萎缩中起作用，这种影响在一定程度上是可以预防或逆转的。
