Department of General Practice, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang 310016, P.R. China.
Department of Acupuncture and Moxibustion, The Third Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou, Zhejiang 310005, P.R. China.
Mol Med Rep. 2018 May;17(5):7293-7300. doi: 10.3892/mmr.2018.8786. Epub 2018 Mar 20.
Alzheimer's disease is one of the most common age‑associated diseases that frequently leads to memory disorders, cognitive decline and dementia. Evidence suggests that nicergoline serves an important role in the apoptosis of hippocampal cells, memory recovery, cognitive function and neuronal survival. However, the signaling pathway affected by nicergoline treatment remains to be elucidated. The purpose of the present study was to investigate the role of nicergoline in the cognitive competence of a mouse model of Alzheimer's disease. The apoptosis rates of hippocampal cells were studied in mice with Alzheimer's disease treated with nicergoline compared with the negative control. Apoptosis‑associated gene expression levels in hippocampal cells, and hippocampus area, were analyzed in the experimental mice. Visual attention and inhibitory control were assessed and neural counting was performed in brain regions of interest. The phosphatidylinositol 3‑kinase (PI3K)/RAC‑α serine/threonine‑protein kinase (AKT) signaling pathway was additionally analyzed in hippocampal cells following treatment with nicergoline. The results of the present study demonstrated that nicergoline ameliorated apoptosis in hippocampal cells and hippocampus tissue in 3xTg‑AD mice with Alzheimer's disease. The data indicated that apoptosis‑associated genes, including caspase‑3, BCL2 associated X, BH3 interacting domain death agonist and caspase‑9, were downregulated in hippocampal cells isolated from nicergoline-treated experimental mice. In addition, the expression levels of inflammatory factors, in addition to oxidative stress, were decreased in hippocampal cells treated with nicergoline. Additionally, amyloid precursor protein accumulation was cleared in the hippocampal area in nicergoline‑treated mice. Nicergoline inhibited neuronal loss and prevented cognitive impairment through the restoration of learning/memory ability. It was additionally demonstrated in the present study that nicergoline improved motor attention impairment and cognitive competence in hippocampal cells by acting on the PI3K/AKT signaling pathway. Therefore, memory recovery, cognitive function and neuronal survival were repaired by nicergoline via inhibition of the PI3K/AKT signaling pathway, suggesting that nicergoline may be an efficient drug for the clinical treatment of patients with Alzheimer's disease.
阿尔茨海默病是最常见的与年龄相关的疾病之一，常导致记忆障碍、认知能力下降和痴呆。有证据表明，麦角碱在海马细胞凋亡、记忆恢复、认知功能和神经元存活中发挥重要作用。然而，麦角碱治疗影响的信号通路仍有待阐明。本研究旨在探讨麦角碱在阿尔茨海默病小鼠模型认知能力中的作用。与阴性对照组相比，研究了阿尔茨海默病小鼠用麦角碱治疗后海马细胞的凋亡率。分析了实验小鼠海马细胞中与凋亡相关的基因表达水平和海马区面积。评估了视觉注意力和抑制控制，并对大脑感兴趣区域进行了神经计数。此外，还分析了麦角碱处理后海马细胞中磷酸肌醇 3-激酶（PI3K）/ Rac-α 丝氨酸/苏氨酸-蛋白激酶（AKT）信号通路。本研究结果表明，麦角碱改善了阿尔茨海默病 3xTg-AD 小鼠海马细胞和海马组织的凋亡。数据表明，海马细胞中凋亡相关基因，包括 caspase-3、BCL2 相关 X、BH3 相互作用域死亡激动剂和 caspase-9，下调。此外，麦角碱处理的海马细胞中炎症因子和氧化应激的表达水平降低。此外，在麦角碱处理的小鼠中，海马区的淀粉样前体蛋白积累被清除。麦角碱通过恢复学习/记忆能力抑制神经元丢失和预防认知障碍。本研究还表明，麦角碱通过作用于 PI3K/AKT 信号通路改善了海马细胞的运动注意力障碍和认知能力。因此，通过抑制 PI3K/AKT 信号通路，麦角碱修复了记忆恢复、认知功能和神经元存活，表明麦角碱可能是治疗阿尔茨海默病患者的有效药物。
