Neural stem cells isolated from amyloid precursor proteinmutated mice for drug discovery

作     者：Vito Antonio Baldassarro Mercedez Fernández Giulia Lizzo Michela Paradisi Luciana Giardino Laura Calzà Giulia Lizzo 

作者机构：Health Science and Technologies Interdepartmental Center for Industrial Research(HST-ICIR) Department of Veterinary Medicine and University of Bologna Health Science and Technolo-gies Interdepartmental Centre for Industrial Research(HST-ICIR)and IRET Foundation Institut de Recherches Servier125 Chemin de Ronde 

出 版 物：《World Journal of Stem Cells》 (世界干细胞杂志（英文版）（电子版）)

年 卷 期：2013年第5卷第4期

页      面：229-237页

学科分类：1001[医学-基础医学(可授医学、理学学位)] 100101[医学-人体解剖与组织胚胎学] 10[医学] 

基　　金：Supported by Regione Emilia Romagna POR-FESR 2011-2014 

主　　题：Neural stem cells Alzheimer’s disease Neuron maturation Drug discovery 

摘      要：AIM: To develop an in vitro model based on neural stem cells derived from transgenic animals, to be used in the study of pathological mechanisms of Alzheimer s disease and for testing new ***: Neural stem cells(NSCs) were isolated from the subventricular zone of Wild type(Wt) and Tg2576 mice. Primary and secondary neurosphere generation was studied, analysing population doubling and the cell yield per animal. Secondary neurospheres were dissociated and plated on MCM Gel Cultrex 2D and after 6 d in vitro(DIVs) in mitogen withdrawal conditions,spontaneous differentiation was studied using specific neural markers(MAP2 and TuJ-1 for neurons, GFAP forastroglial cells and CNPase for oligodendrocytes). Gene expression pathways were analysed in secondary neurospheres, using the QIAGEN PCR array for neurogenesis, comparing the Tg2576 derived cell expression with the Wt cells. Proteins encoded by the altered genes were clustered using STRING web ***: As revealed by 6E10 positive staining, all Tg2576 derived cells retain the expression of the human transgenic Amyloid Precursor Protein. Tg2576 derived primary neurospheres show a decrease in population doubling. Morphological analysis of differentiated NSCs reveals a decrease in MAP2- and an increase in GFAP-positive cells in Tg2576 derived cells. Analysing the branching of TuJ-1 positive cells, a clear decrease in neurite number and length is observed in Tg2576 *** gene expression neurogenesis pathway revealed11 altered genes in Tg2576 NSCs compared to ***: Tg2576 NSCs represent an appropriate AD in vitro model resembling some cellular alterations observed in vivo, both as stem and differentiated cells.