Cairo University, Pharmacology & Toxicology Department, Faculty of Pharmacy, Egypt.
Cairo University, Pharmacology & Toxicology Department, Faculty of Pharmacy, Egypt.
Eur J Pharmacol. 2014 Jan 15;723:330-8. doi: 10.1016/j.ejphar.2013.11.008. Epub 2013 Dec 3.
Alzheimer's disease (AD) is a chronic neurodegenerative disorder that leads to disturbances of cognitive functions. Although the primary cause of AD remains unclear, brain acetylcholine deficiency, oxidative stress and neuroinflammation may be considered the principal pathogenic factors. The present study was constructed to investigate the anti-amnestic effect of pyrrolidine dithiocarbamate (PDTC) on scopolamine-induced behavioral, neurochemical and biochemical changes in rats. PDTC (50 and 100mg/kg) and donepezil (2.5mg/kg) were orally administered for 14 successive days. Dementia was induced at the end of the treatment period by a single injection of scopolamine (20mg/kg; i.p.), and Y-maze test was conducted 30min thereafter. Rats were then sacrificed and homogenates of cortical and hippocampal tissues were used for the estimation of noradrenaline, dopamine, serotonin and heat shock protein 70 contents along with acetylcholinesterase activity. In addition, certain oxidative stress markers, pro-inflammatory and anti-inflammatory cytokines were assessed. Histological examination of cortical and hippocampal tissues was also performed. Scopolamine resulted in memory impairment that was coupled by alterations in the estimated neurotransmitters, heat shock protein 70, acetylcholinesterase activity, oxidative stress as well as inflammatory biomarkers. Histological analysis revealed serious damaging effects of scopolamine on the structure of cerebral cortex and hippocampus. Pretreatment of rats with PDTC in both doses mitigated scopolamine-induced behavioral, biochemical, neurochemical and histological changes in a manner comparable to donepezil. The observed anti-amnestic effect of PDTC makes it a promising candidate for clinical trials in patients with cognitive impairment.
阿尔茨海默病（AD）是一种慢性神经退行性疾病，可导致认知功能障碍。尽管 AD 的主要病因仍不清楚，但脑内乙酰胆碱缺乏、氧化应激和神经炎症可能被认为是主要的致病因素。本研究旨在探讨吡咯烷二硫代氨基甲酸盐（PDTC）对东莨菪碱诱导的大鼠行为、神经化学和生化变化的抗健忘作用。PDTC（50 和 100mg/kg）和多奈哌齐（2.5mg/kg）连续口服 14 天。在治疗期末单次腹腔注射东莨菪碱（20mg/kg）诱导痴呆，然后 30min 后进行 Y 迷宫测试。然后处死大鼠，用皮质和海马组织匀浆测定去甲肾上腺素、多巴胺、5-羟色胺和热休克蛋白 70 的含量以及乙酰胆碱酯酶活性。此外，还评估了某些氧化应激标志物、促炎和抗炎细胞因子。还对皮质和海马组织进行了组织学检查。东莨菪碱导致记忆障碍，同时改变了估计的神经递质、热休克蛋白 70、乙酰胆碱酯酶活性、氧化应激以及炎症生物标志物。组织学分析显示东莨菪碱对大脑皮质和海马体的结构造成了严重的损害。PDTC 以两种剂量预处理大鼠可减轻东莨菪碱诱导的行为、生化、神经化学和组织学变化，其作用与多奈哌齐相当。PDTC 观察到的抗健忘作用使其成为认知障碍患者临床试验的有前途的候选药物。
