Blocking mPTP on neural stem cells and activating the nicotinic acetylcholine receptor α7 subunit on microglia attenuate Aβ-induced neurotoxicity on neural stem cells
Background: β-Amyloid(Aβ)can stimulate microglia to release a variety of proinflammatory cytokines and induce neurotoxicity.Nicotine has been reported to inhibit TNF-α,IL-1,and ROS production in microglia.Mitochondrial permeability transition pore(mPTP)plays an important role in neurotoxicity as well.Here,we investigated whether activating the microglial α7-nAChR has a neuroprotective role on neural stem cells(NSCs)and the function of mPTP in NSCs in this process.Methods: The expression of α7-nAChR in rat NSCs was detected by immunocytochemistry and RT-PCR.The viability of microglia and NSCs was examined by MTT assay.The mitochondrial membrane potential(ΔΨm)and morphological characteristics of NSCs was measured by JC-1 staining and transmission electron microscopy respectively.The distribution of cytochrome c in the subcellular regions of NSCs was visualized by confocal laser scanning microscopy,and the expression levels of cyclophilin D and cleaved caspase-3 were assayed by western blot.The apoptotic rate of NSCs was measured by flow cytometry.Results: The expression of α7-nAChR was detected in microglial cells,but no expression was found in NSCs.The viability of rat microglial cells and NSCs was not affected by reagents or coculture itself.Aβ1-42-mediated microglial activation impaired the morphology and the ΔΨm of mitochondria of NSCs as well as increased cell apoptosis.However,the damage was attenuated when the α7-nAChRs on microglial cells were activated or the mPTPs on NSCs were blocked.Conclusions: Blockade of mPTPs on NSCs and activation of α7-nAChRs on microglia exhibit neuroprotective roles in Aβ-induced neurotoxicity of NSCs.
mitochondrial permeability transition pore microglia neural stem cells inflammatory response β-amyloid nicotinic acetylcholine receptor α7 subunit
Qingzhuang Chen Kewan Wang Deqi Jiang Yan Wang Xiaodan Xiao Ning Zhu Mingxing Li Siyuan Jia Yong Wang
Department of Pharmacy,Southern Medical University,Zhujiang Hosipital,Guangzhou,China;Department of Department of Neurosurgery,Nanfang Hospital,Southern Medical University,Guangzhou China. Department of Pharmacy,Southern Medical University,Zhujiang Hosipital,Guangzhou,China
国内会议
广州
英文
1-39
2016-12-17（万方平台首次上网日期，不代表论文的发表时间）