Wu Lingzhi, Feng Xiaowen, Li Tingting, Sun Baojuan, Khan Muhammad Zahid, He Ling
Department of Pharmacology, China Pharmaceutical University, Nanjing 210009, China.
Department of Pharmacology, China Pharmaceutical University, Nanjing 210009, China.
Behav Brain Res. 2017 Mar 30;322(Pt A):145-156. doi: 10.1016/j.bbr.2017.01.020. Epub 2017 Jan 16.
Alzheimer's disease (AD) is a complex neurodegenerative disorder with cognitive impairment and major neuropathologic hallmark of amyloid-beta (Aβ) peptides. Risperidone, an atypical antipsychotic, can improve concentration and cognitive deficit in schizophrenia patients. In this study, behavior tests including Morris Water Maze test, Step-through passive avoidance test, Open Field test, Step-Down test, Hole-Board test and Novel object recognition test were preformed to examine the effect of Risperidone on Aβ-induced cognitive dysfunction in both long-term and short-term memory. Furthermore, ELISA assay was conducted to measure the levels of Aβ BACE1 and p-Tau in the hippocampus and cortex. Moreover, primary cortical neuron was cultured in vitro, and the cell viability, mitochondrial membrane potential, and the level of p-Akt, GSK3β and Caspase-3 protein were measured. For behavior tests, the results showed that Risperidone significantly reversed the Aβ-induced dysfunction in learning, memory, locomotor activity and exploratory behavior. As detected by ELISA assay, risperidone decreased the levels of Aβ, BACE1 and p-Tau in the hippocampus and cortex of AD model mice. Biochemical assay showed that Risperidone reversed the Aβ-induced decrease of cell viability and mitochondrial membrane potential in cultured cortical neurons. The expression of p-Akt was increased, whereas the expression of GSK3β and Caspase-3 were decreased. These results suggested that Risperidone may be used as a promising candidate for AD treatment, for its effects of inhibiting Aβ generation and improving cognitive impairment in mice.
阿尔茨海默病（AD）是一种复杂的神经退行性疾病，具有认知障碍和β-淀粉样蛋白（Aβ）肽的主要神经病理学特征。利培酮是一种非典型抗精神病药物，可改善精神分裂症患者的注意力和认知缺陷。在本研究中，进行了包括莫里斯水迷宫试验、穿梭式被动回避试验、旷场试验、跳台试验、洞板试验和新物体识别试验在内的行为测试，以研究利培酮对Aβ诱导的长期和短期记忆认知功能障碍的影响。此外，采用酶联免疫吸附测定（ELISA）法检测海马体和皮质中Aβ、β-分泌酶1（BACE1）和磷酸化tau蛋白（p-Tau）的水平。此外，体外培养原代皮质神经元，检测细胞活力、线粒体膜电位以及p-Akt、糖原合成酶激酶3β（GSK3β）和半胱天冬酶-3（Caspase-3）蛋白的水平。行为测试结果显示，利培酮显著逆转了Aβ诱导的学习、记忆、运动活动和探索行为功能障碍。ELISA检测显示，利培酮降低了AD模型小鼠海马体和皮质中Aβ、BACE1和p-Tau的水平。生化分析表明，利培酮逆转了Aβ诱导的培养皮质神经元细胞活力和线粒体膜电位的降低。p-Akt的表达增加，而GSK3β和Caspase-3的表达降低。这些结果表明，利培酮可能是一种有前景的AD治疗候选药物，因为它具有抑制Aβ生成和改善小鼠认知障碍的作用。
