Abdel-Wahab Basel A, Abdel-Wahab Mahmoud M
Department of Pharmacology, College of Medicine, Assiut University, Assiut, Egypt.
Department of Biochemistry and Molecular Biology, Fayoum University, Fayoum, Egypt.
Behav Brain Res. 2016 May 15;305:65-75. doi: 10.1016/j.bbr.2016.02.030. Epub 2016 Mar 3.
Long-term intermittent hypoxia (IH) is a characteristic hallmark of obstructive sleep apnea (OSA) and causes most of the neurological aspects of OSA, such as spatial memory and learning deficits. These deficits are accompanied by an increase in oxidative stress and inflammation in brain areas involved in cognition, such as the hippocampus, particularly in children. Resveratrol is a natural polyphenolic compound with potent antioxidant, anti-inflammatory and neuroprotective properties.
The aim of this work is to study the possible protective effect of resveratrol against IH-induced neurobehavioral deficits and to investigate the possible mechanism of this protective effect in the young rat model of OSA.
The effect of resveratrol (5 and 10mg/kg, orally) on anxiety, spatial memory and learning deficits in young rats exposed to IH for 6 weeks and the corresponding biochemical changes were studied.
Resveratrol attenuated IH-induced anxiety and spatial memory deficits, as indicated by the elevated plus maze and Morris water maze tests, respectively, in a dose-dependent manner. In addition, resveratrol antagonized IH-induced increases in hippocampal glutamate, TBARS and 8-OHdG levels and p47Phox expression and decreases in GSH levels and GSH-Px activity in the hippocampus of IH-exposed young rats.
Resveratrol ameliorates IH-induced anxiety and spatial learning deficits through multiple beneficial effects on hippocampal oxidative pathways that involve decreased expression of the p47Phox subunit of NADPH oxidase. Hence, the potential therapeutic role of resveratrol in OSA may be utilized in the near future and deserves further exploration.
长期间歇性缺氧（IH）是阻塞性睡眠呼吸暂停（OSA）的一个特征性标志，并且导致OSA的大多数神经学方面的问题，如空间记忆和学习缺陷。这些缺陷伴随着认知相关脑区（如海马体）氧化应激和炎症的增加，尤其是在儿童中。白藜芦醇是一种天然多酚化合物，具有强大的抗氧化、抗炎和神经保护特性。
本研究旨在探讨白藜芦醇对IH诱导的神经行为缺陷的可能保护作用，并研究其在年轻大鼠OSA模型中这种保护作用的可能机制。
研究了白藜芦醇（5和10mg/kg，口服）对暴露于IH 6周的年轻大鼠焦虑、空间记忆和学习缺陷的影响以及相应的生化变化。
高架十字迷宫和Morris水迷宫试验分别表明，白藜芦醇以剂量依赖性方式减轻了IH诱导的焦虑和空间记忆缺陷。此外，白藜芦醇拮抗了IH诱导的暴露于IH的年轻大鼠海马体中谷氨酸、丙二醛和8-羟基脱氧鸟苷水平升高以及p47Phox表达增加，以及谷胱甘肽水平降低和谷胱甘肽过氧化物酶活性降低。
白藜芦醇通过对海马体氧化途径的多种有益作用（包括降低NADPH氧化酶p47Phox亚基的表达）改善了IH诱导的焦虑和空间学习缺陷。因此，白藜芦醇在OSA中的潜在治疗作用可能会在不久的将来得到应用，值得进一步探索。
