Xia Zhiming, Wang Fengfei, Zhou Shuang, Zhang Rui, Wang Fushun, Huang Jason H, Wu Erxi, Zhang Yongfang, Hu Yaer
Research Laboratory of Cell Regulation, School of Medicine, Shanghai Jiaotong University, Shanghai 200025, China.
Current address: Department of Nuclear Medicine, Shandong Provincial Hospital, Shandong University, Jinan, Shandong 250021, China.
Oncotarget. 2017 May 17;8(41):69303-69315. doi: 10.18632/oncotarget.17951. eCollection 2017 Sep 19.
Synapse loss is one of the common factors contributing to cognitive disorders, such as Alzheimer's disease (AD), which is manifested by the impairment of basic cognitive functions including memory processing, perception, problem solving, and language. The current therapies for patients with cognitive disorders are mainly palliative; thus, regimens preventing and/or delaying dementia progression are urgently needed. In this study, we evaluated the effects of catalpol, isolated from traditional Chinese medicine on synaptic plasticity in aged rat models. We found that catalpol markedly improved the cognitive function of aged male Sprague-Dawley rats and simultaneously increased the expression of synaptic proteins (dynamin 1, PSD-95, and synaptophysin) in the cerebral cortex and hippocampus, respectively. In beta-amyloid (Aβ) injured primary rat's cortical neuron, catalpol did not increase the viability of neuron but extended the length of microtubule-associated protein 2 (MAP-2) positive neurites and reversed the suppressive effects on expression of synaptic proteins induced by Aβ. Additionally, the effects of catalpol on stimulating the growth of MAP-2 positive neurites and the expression of synaptic proteins were diminished by a PKC inhibitor, bisindolylmaleimide I, suggesting that PKC may be implicated in catalpol's function of preventing the neurodegeneration induced by Aβ. Altogether, our study indicates that catalpol could be a potential disease-modifying drug for cognitive disorders such as AD.
突触丧失是导致认知障碍的常见因素之一，如阿尔茨海默病（AD），其表现为包括记忆处理、感知、问题解决和语言在内的基本认知功能受损。目前针对认知障碍患者的治疗主要是姑息性的；因此，迫切需要预防和/或延缓痴呆进展的治疗方案。在本研究中，我们评估了从中药中分离出的梓醇对老年大鼠模型突触可塑性的影响。我们发现梓醇显著改善了老年雄性Sprague-Dawley大鼠的认知功能，同时分别增加了大脑皮层和海马体中突触蛋白（发动蛋白1、PSD-95和突触素）的表达。在β-淀粉样蛋白（Aβ）损伤的原代大鼠皮层神经元中，梓醇没有增加神经元的活力，但延长了微管相关蛋白2（MAP-2）阳性神经突的长度，并逆转了Aβ对突触蛋白表达的抑制作用。此外，PKC抑制剂双吲哚马来酰亚胺I减弱了梓醇对刺激MAP-2阳性神经突生长和突触蛋白表达的作用，这表明PKC可能参与了梓醇预防Aβ诱导的神经退行性变的功能。总之，我们的研究表明梓醇可能是一种用于治疗如AD等认知障碍的潜在疾病改善药物。
