机构：[a]Department of Interventional Neurology, Beijing Tiantan Hospital, Capital Medical University, Beijing,重点科室诊疗科室神经病学中心神经病学中心首都医科大学附属天坛医院[b]Department of Gastroenterology, First Affiliated Hospital, Henan University, Kaifeng, Henan, China[c]Department of Neurology, First Affiliated Hospital, Henan University, Kaifeng, Henan, China
-Amyloid (A)-induced neuronal toxicity is an early event in the pathogenesis of Alzheimer's disease. Quetiapine (QTP) is an atypical antipsychotic drug that has neuroprotectant properties, but little is known about its direct protective effects on neurons against the A-induced cell toxicity. In the present study, we investigated the neuroprotective effects of QTP on A(25-35)-induced cell death and the possible underlying mechanisms in primary cultures of neurons. Exposure of cortical neurons to 10M or more A(25-35) caused significant viability loss in a MTT assay, and the toxic effects were not significantly prevented by the simultaneous coadministration of QTP. However, pretreated astrocyte conditioned medium (ACM) with QTP (ACM(QTP)) for 24h markedly protected the neurons against the amyloid-induced cell loss. Furthermore, we revealed that QTP increased both the release of brain-derived neurotrophic factor from cultured astrocytes and the phosphorylation of extracellular signal-regulated kinase after 24h of treatment, which might be responsible for its protective effects on neurons. Consistent with the aforementioned findings, the protective effects of ACM on neurons could potentially be abolished by the extracellular signal-regulated kinase inhibitor and tropomyosin receptor kinase B receptor blocker. In conclusion, our data demonstrated that QTP exerted its neuroprotective effects against amyloid toxicity by enhancing the brain-derived neurotrophic factor release from astrocytes.
基金：
Natural Science Foundation of China (NSFC)National Natural Science Foundation of China [81400901]; China Scholarship CouncilChina Scholarship Council
第一作者机构：[a]Department of Interventional Neurology, Beijing Tiantan Hospital, Capital Medical University, Beijing,[c]Department of Neurology, First Affiliated Hospital, Henan University, Kaifeng, Henan, China
通讯作者：
通讯机构：[a]Department of Interventional Neurology, Beijing Tiantan Hospital, Capital Medical University, Beijing,[*1]Department of Neurology, Beijing Tiantan Hospital, Capital Medical University, Beijing 100050, China
推荐引用方式(GB/T 7714)：
Gang Luo,Yinuo Huang,Baixue Jia,et al.Quetiapine prevents A(25-35)-induced cell death in cultured neuron by enhancing brain-derived neurotrophic factor release from astrocyte[J].NEUROREPORT.2018,29(2):92-98.doi:10.1097/WNR.0000000000000911.
APA：
Gang Luo,Yinuo Huang,Baixue Jia,Xuelei Zhang,Dapeng Mo...&Zhongrong Miao.(2018).Quetiapine prevents A(25-35)-induced cell death in cultured neuron by enhancing brain-derived neurotrophic factor release from astrocyte.NEUROREPORT,29,(2)
MLA：
Gang Luo,et al."Quetiapine prevents A(25-35)-induced cell death in cultured neuron by enhancing brain-derived neurotrophic factor release from astrocyte".NEUROREPORT 29..2(2018):92-98
