title: Neural stem cell transplantation enhances mitochondrial biogenesis in a transgenic mouse model of Alzheimer's disease-like pathology.
abstract: Mitochondrial dysfunction, especially a defect in mitochondrial biogenesis, is an early and prominent feature of Alzheimer's disease (AD). Previous studies demonstrated that the number of mitochondria is significantly reduced in susceptible hippocampal neurons from AD patients. Neural stem cell (NSC) transplantation in AD-like mice can compensate for the neuronal loss resulting from amyloid-beta protein deposition. The effects of NSC transplantation on mitochondrial biogenesis and cognitive function in AD-like mice, however, are poorly understood. In this study, we injected NSCs or vehicle into 12-month-old amyloid precursor protein (APP)/PS1 transgenic mice, a mouse model of AD-like pathology. The effects of NSC transplantation on cognitive function, the amount of mitochondrial DNA, the expression of mitochondrial biogenesis factors and mitochondria-related proteins, and mitochondrial morphology were investigated. Our results show that in NSC-injected APP/PS1 (Tg-NSC) mice, the cognitive function, number of mitochondria, and expression of mitochondria-related proteins, specifically the mitochondrial fission factors (dynamin-related protein 1 [Drp1] and fission 1 [Fis1]) and the mitochondrial fusion factor optic atrophy 1 (OPA1), were significantly increased compared with those in age-matched vehicle-injected APP/PS1 (Tg-Veh) mice, whereas the expression of mitochondrial fusion factors mitofusion 1 (Mfn1) and Mfn2 was significantly decreased. These data indicate that NSC transplantation may enhance mitochondria biogenesis and further rescue cognitive deficits in AD-like mice.
authors.affiliation: Department of Medical Imaging, Tongji Hospital, Medical School of Tongji University, Shanghai, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Zhang
authors.affiliation: Department of Medical Imaging, Tongji Hospital, Medical School of Tongji University, Shanghai, China.
authors.forename: Guo-Jun
authors.initials: GJ
authors.lastname: Gu
authors.affiliation: Department of Radiology, Traditional Chinese Hospital, Kun Shan, Jiangsu Province, China.
authors.forename: Xing
authors.initials: X
authors.lastname: Shen
authors.affiliation: Department of Blood Transfusion, Huashan Hospital, Fudan University, Shanghai, China. Electronic address: friday0451@163.com.
authors.forename: Qi
authors.initials: Q
authors.lastname: Zhang
authors.affiliation: Department of Urology, Huashan Hospital, Fudan University, Shanghai, China. Electronic address: 402346583@qq.com.
authors.forename: Gang-Min
authors.initials: GM
authors.lastname: Wang
authors.affiliation: Department of Medical Imaging, Tongji Hospital, Medical School of Tongji University, Shanghai, China. Electronic address: peijunwang_tongji@163.com.
authors.forename: Pei-Jun
authors.initials: PJ
authors.lastname: Wang
mesh_terms: D000544:Alzheimer Disease / Q000235:genetics* / Q000473:pathology / Q000503:physiopathology / Q000628:therapy*; D016229:Amyloid beta-Peptides / Q000378:metabolism; D000818:Animals; D003071:Cognition; D004272:DNA, Mitochondrial / Q000378:metabolism; D004195:Disease Models, Animal; D034281:Dynamins / Q000235:genetics / Q000378:metabolism; D020558:GTP Phosphohydrolases / Q000235:genetics / Q000378:metabolism; D015870:Gene Expression; D008822:Mice, Transgenic; D024101:Mitochondrial Proteins / Q000235:genetics / Q000378:metabolism; D063269:Mitochondrial Turnover / Q000235:genetics; D058953:Neural Stem Cells / Q000637:transplantation*
chemical_list: D016229:Amyloid beta-Peptides; D004272:DNA, Mitochondrial; C561064:FIS1 protein, mouse; D024101:Mitochondrial Proteins; D020558:GTP Phosphohydrolases; C488750:Mfn1 protein, mouse; C498809:Opa1 protein, mouse; C486391:Dnm1l protein, mouse; D034281:Dynamins
keywords: Alzheimer's disease; Cognitive function; Mitochondrial biogenesis; Neural stem cells; Transplantation