Shin Ki Young, Kim Ka Young, Suh Yoo-Hun
Department of Microbiology, College of Natural Science, Dankook University, Cheonan 31116, Korea.
Department of Nursing, College of Nursing, Gachon University, Incheon 21936, Korea.
Korean J Physiol Pharmacol. 2017 Jan;21(1):55-64. doi: 10.4196/kjpp.2017.21.1.55. Epub 2016 Dec 21.
Progressive memory impairment such as that associated with depression, stroke, and Alzheimer's disease (AD) can interfere with daily life. In particular, AD, which is a progressive neurodegenerative disorder, prominently features a memory and learning impairment that is related to changes in acetylcholine and abnormal β-amyloid (Aβ) deposition in the brain. In the present study, we investigated the effects of dehydroevodiamine·HCl (DHED) on cognitive improvement and the related mechanism in memory-impaired rat models, namely, a scopolamine-induced amnesia model and a Aβ-infused model. The cognitive effects of DHED were measured using a water maze test and a passive avoidance test in the memory-impaired rat models. The results demonstrate that DHED (10 mg/kg, p.o.) and Donepezil (1 mg/kg, p.o.) ameliorated the spatial memory impairment in the scopolamine-induced amnestic rats. Moreover, DHED significantly improved learning and memory in the Aβ-infused rat model. Furthermore, the mechanism of these behavioral effects of DHED was investigated using a cell viability assay, reactive oxygen species (ROS) measurement, and intracellular calcium measurement in primary cortical neurons. DHED reduced neurotoxicity and the production of Aβ-induced ROS in primary cortical neurons. In addition, similar to the effect of MK801, DHED decreased intracellular calcium levels in primary cortical neurons. Our results suggest that DHED has strong protective effects against cognitive impairments through its antioxidant activity and inhibition of neurotoxicity and intracellular calcium. Thus, DHED may be an important therapeutic agent for memory-impaired symptoms.
进行性记忆障碍，如与抑郁症、中风和阿尔茨海默病（AD）相关的记忆障碍，会干扰日常生活。特别是AD，它是一种进行性神经退行性疾病，其显著特征是记忆和学习障碍，这与大脑中乙酰胆碱的变化和异常β-淀粉样蛋白（Aβ）沉积有关。在本研究中，我们研究了盐酸吴茱萸碱（DHED）对记忆受损大鼠模型（即东莨菪碱诱导的失忆模型和Aβ注入模型）认知改善的影响及其相关机制。在记忆受损大鼠模型中，使用水迷宫试验和被动回避试验来测量DHED的认知效果。结果表明，DHED（10mg/kg，口服）和多奈哌齐（1mg/kg，口服）改善了东莨菪碱诱导的失忆大鼠的空间记忆障碍。此外，DHED显著改善了Aβ注入大鼠模型的学习和记忆。此外，使用原代皮层神经元的细胞活力测定、活性氧（ROS）测量和细胞内钙测量来研究DHED这些行为效应的机制。DHED降低了原代皮层神经元的神经毒性和Aβ诱导的ROS产生。此外，与MK801的作用类似，DHED降低了原代皮层神经元的细胞内钙水平。我们的结果表明，DHED通过其抗氧化活性以及对神经毒性和细胞内钙的抑制作用，对认知障碍具有强大的保护作用。因此，DHED可能是治疗记忆受损症状的重要药物。
