期刊
NEUROBIOLOGY OF AGING
卷 33, 期 3, 页码 588-602出版社
ELSEVIER SCIENCE INC
DOI: 10.1016/j.neurobiolaging.2010.03.024
关键词
Alzheimer's disease; Human umbilical cord blood-derived mesenchymal stem cell; Amyloid-beta; microglia; Spatial learning and memory; Microglial neuroinflammation
资金
- Korea Science and Engineering Foundation
- Ministry of Education, Science and Technology [R32-10064]
- Ministry of Science and Technology, Republic of Korea [SC4170]
Human umbilical cord blood-derived mesenchymal stem cells (hUCB-MSC) have a potential therapeutic role in the treatment of neurological disorders, but their current clinical usage and mechanism of action has yet to be ascertained in Alzheimer's disease (AD). Here we report that hUCB-MSC transplantation into amyloid precursor protein (APP) and presenilin1 (PS1) double-transgenic mice significantly improved spatial learning and memory decline. Furthermore, amyloid-beta peptide (A beta) deposition, beta-secretase 1 (BACE-1) levels, and tau hyperphosphorylation were dramatically reduced in hUCB-MSC transplanted APP/PS1 mice. Interestingly, these effects were associated with reversal of disease-associated microglial neuroinflammation, as evidenced by decreased microglia-induced proinflammatory cytokines, elevated alternatively activated microglia, and increased anti-inflammatory cytokines. These findings lead us to suggest that hUCB-MSC produced their sustained neuroprotective effect by inducing a feed-forward loop involving alternative activation of microglial neuroinflammation, thereby ameliorating disease pathophysiology and reversing the cognitive decline associated with A beta deposition in AD mice. (C) 2012 Elsevier Inc. All rights reserved.
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