title: Neural stem cell transplantation at critical period improves learning and memory through restoring synaptic impairment in Alzheimer's disease mouse model.
abstract: Alzheimer's disease (AD) is characterized by neuronal loss in several regions of the brain. Recent studies have suggested that stem cell transplantation could serve as a potential therapeutic strategy to halt or ameliorate the inexorable disease progression. However, the optimal stage of the disease for stem cell transplantation to have a therapeutic effect has yet to be determined. Here, we demonstrated that transplantation of neural stem cells into 12-month-old Tg2576 brains markedly improved both cognitive impairments and neuropathological features by reducing β-amyloid processing and upregulating clearance of β-amyloid, secretion of anti-inflammatory cytokines, endogenous neurogenesis, as well as synapse formation. In contrast, the stem cell transplantation did not recover cognitive dysfunction and β-amyloid neuropathology in Tg2576 mice aged 15 months when the memory loss is manifest. Overall, this study underscores that stem cell therapy at optimal time frame is crucial to obtain maximal therapeutic effects that can restore functional deficits or stop the progression of AD.
authors.affiliation: Department of Pharmacology, College of Medicine, Neuroscience Research Institute, MRC, Seoul National University, Seoul, 110-799, Korea.
authors.forename: J A
authors.initials: JA
authors.lastname: Kim
authors.affiliation: Department of Pharmacology, College of Medicine, Neuroscience Research Institute, Gachon University, Incheon, 405-760, Korea.
authors.forename: S
authors.initials: S
authors.lastname: Ha
authors.affiliation: Department of Pharmacology, College of Medicine, Neuroscience Research Institute, MRC, Seoul National University, Seoul, 110-799, Korea.
authors.forename: K Y
authors.initials: KY
authors.lastname: Shin
authors.affiliation: Department of Pharmacology, College of Medicine, Neuroscience Research Institute, Gachon University, Incheon, 405-760, Korea.
authors.forename: S
authors.initials: S
authors.lastname: Kim
authors.affiliation: Synaptic Circuit Plasticity Laboratory, Department of Structure & Function of Neural Network, Korea Brain Research Institute, 61 Cheomdan-ro, Dong-gu, Daegu 701-300, Korea.
authors.forename: K J
authors.initials: KJ
authors.lastname: Lee
authors.affiliation: Division of Molecular Biology and Neuroscience, Department of Microbiology, School of Medicine, Ewha Medical Research Institute, Ewha Womans University, Seoul, 158-710, Korea.
authors.forename: Y H
authors.initials: YH
authors.lastname: Chong
authors.affiliation: Department of Pharmacology, College of Medicine, Neuroscience Research Institute, Gachon University, Incheon, 405-760, Korea.
authors.forename: K-A
authors.initials: KA
authors.lastname: Chang
authors.affiliation: 1] Department of Pharmacology, College of Medicine, Neuroscience Research Institute, MRC, Seoul National University, Seoul, 110-799, Korea [2] Synaptic Circuit Plasticity Laboratory, Department of Structure & Function of Neural Network, Korea Brain Research Institute, 61 Cheomdan-ro, Dong-gu, Daegu 701-300, Korea.
authors.forename: Y-H
authors.initials: YH
authors.lastname: Suh
mesh_terms: D000544:Alzheimer Disease / Q000628:therapy*; D016229:Amyloid beta-Peptides / Q000378:metabolism; D000818:Animals; D001921:Brain / Q000601:surgery; D064987:Cell- and Tissue-Based Therapy / Q000379:methods*; D002478:Cells, Cultured; D003072:Cognition Disorders / Q000473:pathology / Q000628:therapy; D016207:Cytokines / Q000378:metabolism; D004195:Disease Models, Animal; D018782:Maze Learning / Q000502:physiology*; D008568:Memory / Q000502:physiology*; D008569:Memory Disorders / Q000473:pathology / Q000628:therapy; D051379:Mice; D008810:Mice, Inbred C57BL; D058953:Neural Stem Cells / Q000637:transplantation*; D055495:Neurogenesis / Q000502:physiology
chemical_list: D016229:Amyloid beta-Peptides; D016207:Cytokines