u-0126 and dihydroethidium

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.

Topics: Amyloid beta-Peptides; Animals; Apoptosis; Bone Marrow Transplantation; Butadienes; Cells, Cultured; CREB-Binding Protein; Disease Models, Animal; Embryo, Mammalian; Enzyme Inhibitors; Ethidium; Extracellular Signal-Regulated MAP Kinases; Hippocampus; In Situ Nick-End Labeling; Maze Learning; Memory Disorders; Mesenchymal Stem Cell Transplantation; Mice; Mice, Inbred C57BL; Neurons; Nitriles; Oxidative Stress; Phosphorylation; Reaction Time; Statistics, Nonparametric; Superoxides