title: Blocking mPTP on Neural Stem Cells and Activating the Nicotinic Acetylcholine Receptor α7 Subunit on Microglia Attenuate Aβ-Induced Neurotoxicity on Neural Stem Cells.
abstract: 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. 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. 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. Blockade of mPTPs on NSCs and activation of α7-nAChRs on microglia exhibit neuroprotective roles in Aβ-induced neurotoxicity of NSCs.
authors.affiliation: Department of Pharmacy, Southern Medical University, Zhujiang Hospital, Guangzhou, China.|Department of Clinical Pharmacy, Guangzhou Hospital of Integrated Traditional and Western Medicine, Guangzhou, China.
authors.forename: Qingzhuang
authors.initials: Q
authors.lastname: Chen
authors.affiliation: Department of Neurosurgery, Nanfang Hospital, Southern Medical University, Guangzhou, China.
authors.forename: Kewan
authors.initials: K
authors.lastname: Wang
authors.affiliation: Department of Pharmacy, Southern Medical University, Zhujiang Hospital, Guangzhou, China.
authors.forename: Deqi
authors.initials: D
authors.lastname: Jiang
authors.affiliation: Department of Pharmacy, Southern Medical University, Zhujiang Hospital, Guangzhou, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of Pharmacy, Southern Medical University, Zhujiang Hospital, Guangzhou, China.
authors.forename: Xiaodan
authors.initials: X
authors.lastname: Xiao
authors.affiliation: Department of Pharmacy, Southern Medical University, Zhujiang Hospital, Guangzhou, China.
authors.forename: Ning
authors.initials: N
authors.lastname: Zhu
authors.affiliation: Department of Pharmacy, Southern Medical University, Zhujiang Hospital, Guangzhou, China.
authors.forename: Mingxing
authors.initials: M
authors.lastname: Li
authors.affiliation: Department of Pharmacy, Southern Medical University, Zhujiang Hospital, Guangzhou, China.
authors.forename: Siyuan
authors.initials: S
authors.lastname: Jia
authors.affiliation: Department of Pharmacy, Southern Medical University, Zhujiang Hospital, Guangzhou, China. yongwh2005@163.com.
authors.forename: Yong
authors.initials: Y
authors.lastname: Wang
mesh_terms: D016229:Amyloid beta-Peptides / Q000633:toxicity*; D000818:Animals; D000831:Animals, Newborn; D002478:Cells, Cultured; D017628:Microglia / Q000187:drug effects / Q000378:metabolism*; D033681:Mitochondrial Membrane Transport Proteins / Q000037:antagonists & inhibitors* / Q000378:metabolism*; D000083162:Mitochondrial Permeability Transition Pore; D058953:Neural Stem Cells / Q000187:drug effects / Q000378:metabolism*; D010446:Peptide Fragments / Q000633:toxicity*; D021122:Protein Subunits / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D064569:alpha7 Nicotinic Acetylcholine Receptor / Q000378:metabolism*
chemical_list: D016229:Amyloid beta-Peptides; D033681:Mitochondrial Membrane Transport Proteins; D000083162:Mitochondrial Permeability Transition Pore; D010446:Peptide Fragments; D021122:Protein Subunits; D064569:alpha7 Nicotinic Acetylcholine Receptor; C075222:amyloid beta-protein (1-42)
keywords: Inflammatory response; Microglia; Mitochondrial permeability transition pore; Neural stem cells; Nicotinic acetylcholine receptor α7 subunit; β-Amyloid