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Bone Marrow-Derived Mesenchymal Stem Cells Attenuate Amyloid β-Induced Memory Impairment and Apoptosis by Inhibiting Neuronal Cell Death

[ Vol. 7 , Issue. 6 ]

Author(s):

J. K. Lee, H. K. Jin and J.-S. Bae   Pages 540 - 548 ( 9 )

Abstract:


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 Alzheimers 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.

Keywords:

Acutely induced Alzheimer's disease mouse model, bone marrow-derived mesenchymal stem cell, spatial learning and memory, apoptosis, transplantation

Affiliation:

School of Medicine, Kyungpook National University, 101 Dongindong 2Ga, Jung-Gu, Daegu 700-422, South Korea.



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