Bone marrow-derived mesenchymal stem cells attenuate amyloid β-induced memory impairment and apoptosis by inhibiting neuronal cell death.
Amyloid β (Aβ) peptide plays a central role in neuronal apoptosis, promoting oxidative stress, lipid peroxidation, caspase pathway activation and neuronal loss. Our previous study has shown that bone marrow-derived mesenchymal stem cells (BM-MSCs) reduce Aβ deposition when transplanted into acutely-induced Alzheimer's disease (AD) mice brain. However, the impact of reduced Aβ deposition on memory impairment and apoptosis by BM-MSCs has not yet been investigated. Therefore, the aim of the present study was to investigate the neuroprotective mechanism of BM-MSCs in vitro and in vivo. We found that BM-MSCs attenuated Aβ-induced apoptotic cell death in primary cultured hippocampal neurons by activation of the cell survival signaling pathway. These anti-apoptotic effects of BM-MSCs were also observed in an acutely-induced AD mice model produced by injecting Aβ intrahippocampally. In addition, BM-MSCs diminished Aβ -induced oxidative stress and spatial memory impairment in the in vivo model. These findings lead us to hypothesize that BM-MSCs ameliorate Aβ -induced neurotoxicity and cognitive decline by inhibiting apoptotic cell death and oxidative stress in the hippocampus. These findings provide support for a potentially beneficial role for BM-MSCs in the treatment of AD.
Lee
J K
JK
Stem Cell Neuroplasticity Research Group, Kyungpook National University, Daegu, Korea.
Jin
H K
HK
Bae
J-S
JS
D016229:Amyloid beta-Peptides / Q000009:adverse effects*; D000818:Animals; D017209:Apoptosis / Q000187:drug effects* / Q000502:physiology; D016026:Bone Marrow Transplantation / Q000379:methods*; D002070:Butadienes / Q000494:pharmacology; D050882:CREB-Binding Protein / Q000378:metabolism; D002478:Cells, Cultured; D004195:Disease Models, Animal; D004622:Embryo, Mammalian; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004996:Ethidium / Q000031:analogs & derivatives / Q000378:metabolism; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D006624:Hippocampus / Q000166:cytology; D020287:In Situ Nick-End Labeling / Q000379:methods; D018782:Maze Learning / Q000187:drug effects; D008569:Memory Disorders / Q000139:chemically induced / Q000473:pathology / Q000601:surgery; D045164:Mesenchymal Stem Cell Transplantation / Q000379:methods*; D051379:Mice; D008810:Mice, Inbred C57BL; D009474:Neurons / Q000187:drug effects*; D009570:Nitriles / Q000494:pharmacology; D018384:Oxidative Stress / Q000187:drug effects; D010766:Phosphorylation; D011930:Reaction Time / Q000187:drug effects; D018709:Statistics, Nonparametric; D013481:Superoxides / Q000378:metabolism
D016229:Amyloid beta-Peptides; D002070:Butadienes; D004791:Enzyme Inhibitors; D009570:Nitriles; C113580:U 0126; C067883:dihydroethidium; D013481:Superoxides; D050882:CREB-Binding Protein; D048049:Extracellular Signal-Regulated MAP Kinases; D004996:Ethidium