Abstract
Neurogenesis in the subgranular zone of the hippocampal dentate gyrus may act as an endogenous repair mechanism in Alzheimer's disease (AD), and the Wnt signaling pathway has been suggested to closely modulate neurogenesis in amyloid-β (Aβ)-related AD models. The present study investigated whether mesenchymal stem cells (MSCs) would modulate hippocampal neurogenesis via modulation of the Wnt signaling pathway in a model of AD. In Aβ-treated neuronal progenitor cells (NPCs), the coculture with MSCs increased significantly the expression of Ki-67, GFAP, SOX2, nestin, and HuD compared to Aβ treatment alone. In addition, MSC treatment in Aβ-treated NPCs enhanced the expression of β-catenin and Ngn1 compared to Aβ treatment alone. MSC treatment in Aβ-treated animals significantly increased the number of BrdU-ir cells in the hippocampus at 2 and 4 weeks compared to Aβ treatment alone. In addition, quantitative analysis showed that the number of BrdU and HuD double-positive cells in the dentate gyrus was significantly higher in the MSC-treated group than in controls or after Aβ treatment alone. These results demonstrate that MSC administration significantly augments hippocampal neurogenesis and enhances the differentiation of NPCs into mature neurons in AD models by augmenting the Wnt signaling pathway. The use of MSCs to modulate endogenous adult neurogenesis may have a significant impact on future strategies for AD treatment.
| Original language | English |
|---|---|
| Pages (from-to) | 1097-1109 |
| Number of pages | 13 |
| Journal | Cell transplantation |
| Volume | 24 |
| Issue number | 6 |
| DOIs | |
| Publication status | Published - 2015 Jan 1 |
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All Science Journal Classification (ASJC) codes
- Biomedical Engineering
- Cell Biology
- Transplantation
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Mesenchymal Stem Cells Increase Hippocampal Neurogenesis and Neuronal Differentiation by Enhancing the Wnt Signaling Pathway in an Alzheimer's Disease Model. / Oh, Se H.ee; Kim, Ha N.a.; Park, Hyun Jung; Shin, Jin Y.oung; Lee, Phil H.yu.
In: Cell transplantation, Vol. 24, No. 6, 01.01.2015, p. 1097-1109.Research output: Contribution to journal › Article
TY - JOUR
T1 - Mesenchymal Stem Cells Increase Hippocampal Neurogenesis and Neuronal Differentiation by Enhancing the Wnt Signaling Pathway in an Alzheimer's Disease Model
AU - Oh, Se H.ee
AU - Kim, Ha N.a.
AU - Park, Hyun Jung
AU - Shin, Jin Y.oung
AU - Lee, Phil H.yu
PY - 2015/1/1
Y1 - 2015/1/1
N2 - Neurogenesis in the subgranular zone of the hippocampal dentate gyrus may act as an endogenous repair mechanism in Alzheimer's disease (AD), and the Wnt signaling pathway has been suggested to closely modulate neurogenesis in amyloid-β (Aβ)-related AD models. The present study investigated whether mesenchymal stem cells (MSCs) would modulate hippocampal neurogenesis via modulation of the Wnt signaling pathway in a model of AD. In Aβ-treated neuronal progenitor cells (NPCs), the coculture with MSCs increased significantly the expression of Ki-67, GFAP, SOX2, nestin, and HuD compared to Aβ treatment alone. In addition, MSC treatment in Aβ-treated NPCs enhanced the expression of β-catenin and Ngn1 compared to Aβ treatment alone. MSC treatment in Aβ-treated animals significantly increased the number of BrdU-ir cells in the hippocampus at 2 and 4 weeks compared to Aβ treatment alone. In addition, quantitative analysis showed that the number of BrdU and HuD double-positive cells in the dentate gyrus was significantly higher in the MSC-treated group than in controls or after Aβ treatment alone. These results demonstrate that MSC administration significantly augments hippocampal neurogenesis and enhances the differentiation of NPCs into mature neurons in AD models by augmenting the Wnt signaling pathway. The use of MSCs to modulate endogenous adult neurogenesis may have a significant impact on future strategies for AD treatment.
AB - Neurogenesis in the subgranular zone of the hippocampal dentate gyrus may act as an endogenous repair mechanism in Alzheimer's disease (AD), and the Wnt signaling pathway has been suggested to closely modulate neurogenesis in amyloid-β (Aβ)-related AD models. The present study investigated whether mesenchymal stem cells (MSCs) would modulate hippocampal neurogenesis via modulation of the Wnt signaling pathway in a model of AD. In Aβ-treated neuronal progenitor cells (NPCs), the coculture with MSCs increased significantly the expression of Ki-67, GFAP, SOX2, nestin, and HuD compared to Aβ treatment alone. In addition, MSC treatment in Aβ-treated NPCs enhanced the expression of β-catenin and Ngn1 compared to Aβ treatment alone. MSC treatment in Aβ-treated animals significantly increased the number of BrdU-ir cells in the hippocampus at 2 and 4 weeks compared to Aβ treatment alone. In addition, quantitative analysis showed that the number of BrdU and HuD double-positive cells in the dentate gyrus was significantly higher in the MSC-treated group than in controls or after Aβ treatment alone. These results demonstrate that MSC administration significantly augments hippocampal neurogenesis and enhances the differentiation of NPCs into mature neurons in AD models by augmenting the Wnt signaling pathway. The use of MSCs to modulate endogenous adult neurogenesis may have a significant impact on future strategies for AD treatment.
UR - http://www.scopus.com/inward/record.url?scp=84991223151&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84991223151&partnerID=8YFLogxK
U2 - 10.3727/096368914X679237
DO - 10.3727/096368914X679237
M3 - Article
C2 - 24612635
AN - SCOPUS:84991223151
VL - 24
SP - 1097
EP - 1109
JO - Cell Transplantation
JF - Cell Transplantation
SN - 0963-6897
IS - 6
ER -