title: Co-culturing improves the OGD-injured neuron repairing and NSCs differentiation via Notch pathway activation.
abstract: Neural stem cell (NSC) transplantation for ischemic stroke is expected to repair the neuronal injury and replace the lost neurons through cell-cell cross talk between injured neurons and the transplanted NSCs. Here, we set up an in vitro co-culturing system of oxygen-glucose deprivation (OGD) injured neurons and NSCs to investigate the neuronal repairing effect and effects on NSCs differentiation. We focused on the Notch1 pathway as a possible mediator of these effects. OGD-injured neurons induced increased activation of Notch1 in co-cultured NSCs, through the up-regulations of the DLL1, the Notch1 intracellular domain (NICD) and the down-stream genes Hes1/5. When the NSCs were pre-treated with the Notch pathway inhibitor DAPT, the activation of Notch1 was blocked, lower NSCs differentiation was detected and the neurotrophic effect was also abolished. As shown by the novel co-culturing system, the NSCs co-cultured with OGD injured neurons were induced to differentiate through the Notch1 pathway activation; and these induced NSCs showed greater potential to support both the repair of injured neurons and form new neurons.
authors.affiliation: Department of Neurology, Jinling Hospital, Nanjing University School of Medicine, 305 East Zhongshan Road, Nanjing 210002, Jiangsu, China; School of Dentistry, Cardiff Institute of Tissue Engineering & Repair, Cardiff University, Heath Park, Cardiff, CF14 4XY, UK.
authors.forename: Qian
authors.initials: Q
authors.lastname: Liu
authors.affiliation: Department of Neurology, Jinling Hospital, Nanjing University School of Medicine, 305 East Zhongshan Road, Nanjing 210002, Jiangsu, China.
authors.forename: Xinying
authors.initials: X
authors.lastname: Fan
authors.affiliation: Department of Neurology, Jinling Hospital, Nanjing University School of Medicine, 305 East Zhongshan Road, Nanjing 210002, Jiangsu, China.
authors.forename: Juehua
authors.initials: J
authors.lastname: Zhu
authors.affiliation: Department of Neurology, Jinling Hospital, Nanjing University School of Medicine, 305 East Zhongshan Road, Nanjing 210002, Jiangsu, China.
authors.forename: Gelin
authors.initials: G
authors.lastname: Xu
authors.affiliation: Department of Neurology, Jinling Hospital, Nanjing University School of Medicine, 305 East Zhongshan Road, Nanjing 210002, Jiangsu, China.
authors.forename: Yun
authors.initials: Y
authors.lastname: Li
authors.affiliation: Department of Neurology, Jinling Hospital, Nanjing University School of Medicine, 305 East Zhongshan Road, Nanjing 210002, Jiangsu, China. Electronic address: xfliu2@vip.163.com.
authors.forename: Xinfeng
authors.initials: X
authors.lastname: Liu
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000502:physiology*; D015687:Cell Hypoxia / Q000502:physiology; D002478:Cells, Cultured; D018920:Coculture Techniques; D005947:Glucose / Q000378:metabolism*; D051379:Mice; D058953:Neural Stem Cells / Q000378:metabolism*; D009474:Neurons / Q000378:metabolism* / Q000473:pathology; D051881:Receptor, Notch1 / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology*
chemical_list: C497762:Notch1 protein, mouse; D051881:Receptor, Notch1; D005947:Glucose
keywords: BSA; Co-culture; DAPT; GFAP; Hes; MAP-2; N-[N-(3,5-difluorophenacetyl)-l-alanyl]-S-phenylglycine t-butylester; NICD; NSCs; NSCs differentiation; Neural stem cells; Neuronal oxygen-glucose deprivation injury; Notch intra-cellular domain; Notch1; OGD; albumin from bovine serum; glial fibrillary acidic protein; hairy enhancer of split; microtubule-associated protein 2; neural stem cells; oxygen-glucose deprivation