Reply to Kawada: Obstructive Sleep Apnea and Cognitive Decline in Older Adults.
Reply to Kawada: Obstructive Sleep Apnea and Cognitive Decline in Older Adults.
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回复川田：老年人的阻塞性睡眠呼吸暂停和认知能力下降。
DOI：
10.1164/rccm.201812-2280le
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发表时间：
2019
影响因子：
24.7
通讯作者：
Gosselin,Nadia
中科院分区：
文献类型：
--
作者：
Baril,Andrée-Ann;Osorio,RicardoS;Carrier,Julie;Kaminska,Marta;Gosselin,Nadia
在我们的综述发表后（1），Kawada博士在给编辑的一封信中提出了重要的评论，强调血清胰岛素和大脑中的胰岛素活性可能在阻塞性睡眠呼吸暂停（OSA）和认知能力下降之间的关系中发挥作用。在主要包括中年受试者的研究中，OSA与胰岛素抵抗（IR）和II型糖尿病（T2 DM）的风险较高相关（2）。当组织对胰岛素没有有效反应时，就会发生IR，因此需要更高的水平来保持血糖水平正常。当个体不能跟上这种增加的内源性胰岛素产生/分泌时，葡萄糖水平开始升高，糖尿病恶化。许多潜在的机制已被提出来解释OSA和IR/T2 DM之间的这种关系。OSA引起的间歇性低氧血症和睡眠碎片导致炎症、氧化应激和交感神经系统活动增加（2），所有这些都有可能增加IR并导致T2 DM（2）。OSA可能在IR/T2 DM的病理生理学中发挥因果作用，因为据报道，OSA治疗（持续气道正压通气治疗）可改善胰岛素敏感性（2），尽管并非所有研究都显示了该效果。与老年人相比，在中年人中，OSA与代谢综合征的相关性更强，代谢综合征是一种以向心性肥胖、高血压、血脂异常和葡萄糖控制障碍（包括IR）为特征的疾病（3）。因此，重要的是要考虑中年与晚年OSA对代谢，血管和认知结果的影响。当脑中存在IR时，或当血脑屏障处的胰岛素转运蛋白由于外周IR后的代偿性高胰岛素血症而下调时，可观察到脑胰岛素活性改变（4）。胰岛素活性的改变被假设会影响认知健康。除了在葡萄糖代谢中的作用外，胰岛素还参与最终影响突触可塑性的信号转导级联反应（4）。事实上，胰岛素通过调节N-甲基-D-天冬氨酸受体的表达参与长时程增强。此外，胰岛素调节神经递质和一氧化氮水平，从而可能在血管和认知功能中发挥作用（4）。在人类和动物研究中，IR与认知缺陷相关（4）。有趣的是，在最近的一项荟萃分析中，Cao及其同事研究了几种抗糖尿病药物的作用，并得出结论，这些药物与随机临床试验中轻度认知障碍或阿尔茨海默病（AD）患者的认知表现改善相关（5）。事实上，IR/T2 DM与认知功能障碍、认知能力下降和痴呆风险增加有关（4）。然而，IR和AD之间的联系似乎不涉及经典AD病理学，因为患有T2 DM的人在死后没有显示出斑块和缠结增加（6）。胰岛素功能受损的痴呆症风险增加的另一种机制是基于这两种疾病共有的代谢和脑血管异常。总之，虽然OSA是中年人IR/T2 DM的危险因素，这反过来又会增加认知能力下降和痴呆的风险，但目前还没有足够的证据表明IR/T2 DM可能是解释这些相关性的机制之一。也就是说，OSA和IR/T2 DM表现出相似的病理机制，因此这些病症的伴随存在可能导致对大脑的附加损伤。然而，由于相互之间的...
After the publication of our review (1), Dr. Kawada raised important comments in a letter to the editor, highlighting that serum insulin and insulin activity in the brain could play a role in the relationship between obstructive sleep apnea (OSA) and cognitive decline. OSA has been associated with a higher risk of insulin resistance (IR) and type II diabetes mellitus (T2DM)(2) in studies that included mostly middle-aged subjects. IR occurs when tissues do not respond effectively to insulin, and thus higher levels are required to keep blood glucose levels normal. When an individual cannot keep up with this increased endogenous insulin production/secretion, glucose levels start to rise and diabetes ensues. Many potential mechanisms have been proposed to explain this relationship between OSA and IR/T2DM. Intermittent hypoxemia and sleep fragmentation caused by OSA lead to inflammation, oxidative stress, and increased sympathetic nervous system activity (2), all of which have the potential to increase IR and lead to T2DM (2). OSA may play a causal role in the pathophysiology of IR/T2DM, as insulin sensitivity was reported to be improved by a treatment for OSA (continuous positive airway pressure therapy)(2), although not all studies have shown that effect. In middle-aged individuals compared with the elderly, OSA is more strongly associated with metabolic syndrome, a condition characterized by central obesity, hypertension, dyslipidemia, and impairments in glucose control, including IR (3). Therefore, it is important to consider the effects of OSA in middle age versus late life on metabolic, vascular, and cognitive outcomes. Altered cerebral insulin activity can be observed when there is IR in the brain, or when insulin transporters at the blood–brain barrier are downregulated as a result of the compensatory hyperinsulinemia that follows peripheral IR (4). Altered insulin activity has been hypothesized to affect cognitive health. In addition to its role in glucose metabolism, insulin is involved in a signal transduction cascade that ultimately affects synaptic plasticity (4). In fact, insulin is involved in long-term potentiation by modulating the expression of N-methyl-D-aspartate receptors. Moreover, insulin modulates neurotransmitter and nitric oxide levels, and thereby may play a role in vascular and cognitive functions (4). IR has been associated with cognitive deficits in both human and animal studies (4). Interestingly, in a recent meta-analysis, Cao and colleagues investigated the effects of several antidiabetic agents and concluded that these agents were associated with improved cognitive performance in patients with mild cognitive impairment or Alzheimer’s disease (AD) in randomized clinical trials (5). In fact, IR/T2DM is associated with cognitive impairment, cognitive decline, and increased risk of dementia (4). However, the connection between IR and AD does not appear to involve classic AD pathology, as humans with T2DM do not show increased plaques and tangles postmortem (6). An alternative mechanism proposed for the added risk of dementia with impaired insulin function is based on the metabolic and cerebrovascular abnormalities shared by the two conditions. In summary, although OSA is a risk factor for IR/T2DM in middle-aged individuals, which in turn could increase the risks of cognitive decline and dementia, there is currently not enough evidence to conclude that IR/T2DM might be one of the mechanisms that explain these associations. That said, OSA and IR/T2DM present similar pathological mechanisms, and thus the concomitant presence of these conditions may lead to an additive insult to the brain. However, given the interaction between …
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影响因子：
11.4
作者：
HUGHES, JMX;KONINGS, DAM;CESARENI, G
通讯作者：
CESARENI, G
U8小核RNA的一级和二级结构。
DOI：
10.1016/s0021-9258(17)39124-x
发表时间：
1985
期刊：
The Journal of biological chemistry
影响因子：
--
作者：
R. Reddy;D. Henning;H. Busch
通讯作者：
H. Busch
Xenopus U3 snRNA 的核苷酸序列测定和二级结构。
影响因子：
14.9
作者：
Jeppesen,C;Stebbins-Boaz,B;Gerbi,SA
通讯作者：
Gerbi,SA
使用上游启动子元件和保守基因内区域特异的引物扩增植物 U3 和 U6 snRNA 基因序列。
影响因子：
14.9
作者：
C. Marshallsay;Tamás Kiss;Witold Filipowicz
通讯作者：
Witold Filipowicz
U3 snRNA 的 5 末端可以在体内与大鼠核糖体 RNA 前体的外部转录间隔区交联。
影响因子：
5.6
作者：
Stroke,IL;Weiner,AM
通讯作者：
Weiner,AM