National Institute of Mental Health, Topolova 748, 250 67 Klecany, Czech Republic.
Institute of Computer Science, Academy of Sciences of the Czech Republic, Pod vodarenskou vezi 2, 182 07 Prague 8, Czech Republic.
Int J Mol Sci. 2019 Jul 3;20(13):3273. doi: 10.3390/ijms20133273.
Aging and chronic sleep deprivation (SD) are well-recognized risk factors for Alzheimer's disease (AD), with N-methyl-D-aspartate receptor (NMDA) and downstream nitric oxide (NO) signalling implicated in the process. Herein, we investigate the impact of the age- and acute or chronic SD-dependent changes on the expression of NMDA receptor subunits (NR1, NR2A, and NR2B) and on the activities of NO synthase (NOS) isoforms in the cortex of Wistar rats, with reference to cerebral lateralization. In young adult controls, somewhat lateralized seasonal variations in neuronal and endothelial NOS have been observed. In aged rats, overall decreases in NR1, NR2A, and NR2B expression and reduction in neuronal and endothelial NOS activities were found. The age-dependent changes in NR1 and NR2B significantly correlated with neuronal NOS in both hemispheres. Changes evoked by chronic SD (dysfunction of endothelial NOS and the increasing role of NR2A) differed from those evoked by acute SD (increase in inducible NOS in the right side). Collectively, these results demonstrate age-dependent regulation of the level of NMDA receptor subunits and downstream NOS isoforms throughout the rat brain, which could be partly mimicked by SD. As described herein, age and SD alterations in the prevalence of NMDA receptors and NOS could contribute towards cognitive decline in the elderly, as well as in the pathobiology of AD and the neurodegenerative process.
衰老是慢性睡眠剥夺（SD）是阿尔茨海默病（AD）的公认危险因素，N-甲基-D-天冬氨酸受体（NMDA）和下游的一氧化氮（NO）信号转导与此过程有关。在此，我们研究了年龄和急性或慢性 SD 依赖性变化对 Wistar 大鼠皮质中 NMDA 受体亚基（NR1、NR2A 和 NR2B）表达和 NO 合酶（NOS）同工型活性的影响，并参考了大脑偏侧性。在年轻的成年对照组中，观察到神经元和内皮型 NOS 存在有些偏侧化的季节性变化。在老年大鼠中，发现 NR1、NR2A 和 NR2B 的表达整体减少，神经元和内皮型 NOS 活性降低。NR1 和 NR2B 的年龄依赖性变化与两个半球的神经元 NOS 显著相关。慢性 SD 引起的变化（内皮型 NOS 功能障碍和 NR2A 作用增加）与急性 SD 引起的变化（右侧诱导型 NOS 增加）不同。总的来说，这些结果表明 NMDA 受体亚基和下游 NOS 同工型的水平在整个大鼠大脑中存在年龄依赖性调节，SD 可以部分模拟这种调节。如本文所述，NMDA 受体和 NOS 的年龄和 SD 改变可能导致老年人认知能力下降，以及 AD 的病理生物学和神经退行性过程。
