PDF(Pubmed)
Abstract：
P301S transgenic mice are an animal model of tauopathy and Alzheimer\'s disease (AD), exhibiting tau pathology and synaptic dysfunction. Cornel iridoid glycoside (CIG) is an active ingredient extracted from Cornus officinalis, a traditional Chinese herb. In the present study, the purpose was to investigate the effects and mechanisms of CIG on tau pathology and synaptic dysfunction using P301S transgenic mice. The results showed that intragastric administration of CIG for 3.5 months improved cognitive impairments and the survival rate of P301S mice. Electrophysiological recordings and transmission electron microscopy study showed that CIG improved synaptic plasticity and increased the ultrastructure and number of synapse. Moreover, CIG increased the expression levels of N-methyl-D-aspartate receptors (NMDAR) subunits GluN1, GluN2A, and GluN2B, and α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid receptor (AMPAR) subunit GluA1. We inferred that the major mechanism of CIG involving in the regulation of synaptic dysfunctions was inhibiting the activation of Janus kinase-2 (JAK2)/signal transducer and activator of transcription 1 (STAT1) signaling pathway and alleviating STAT1-induced suppression of NMDAR expressions. Based on our findings, we thought CIG might be a promising candidate for the therapy of tauopathy such as AD.
摘要：
P301S转基因小鼠是Tau蛋白病和阿尔茨海默病(AD)的动物模型,表现出tau病理和突触功能障碍。山茱萸环烯醚萜苷（CIG）是从山茱萸中提取的活性成分，一种传统的中草药。在本研究中,目的是用P301S转基因小鼠研究CIG对tau病理和突触功能障碍的影响和机制。结果表明，灌胃CIG3.5个月可改善P301S小鼠的认知障碍和存活率。电生理记录和透射电镜研究表明，CIG改善了突触可塑性，增加了突触的超微结构和数量。此外，CIG增加了N-甲基-D-天冬氨酸受体（NMDAR）亚基GluN1，GluN2A，和GluN2B,和α-氨基-3-羟基-5-甲基-4-异恶唑丙酸受体（AMPAR）亚基GluA1。我们推断，CIG参与突触功能障碍调节的主要机制是抑制Janus激酶2（JAK2）/信号转导和转录激活因子1（STAT1）信号通路的激活，减轻STAT1诱导的NMDAR表达抑制。根据我们的发现,我们认为CIG可能是治疗tau蛋白病变如AD的有希望的候选药物。
