Amyloid beta-derived neuroplasticity in bone marrow-derived mesenchymal stem cells is mediated by NPY and 5-HT2B receptors via ERK1/2 signalling pathways.
Cell Prolif
; 42(5): 571-86, 2009 Oct.
Article
in En
| MEDLINE
| ID: mdl-19614678
ABSTRACT
OBJECTIVE:
In Alzheimer's disease, toxic soluble and insoluble forms of amyloid beta (Abeta) cause synaptic dysfunction and neuronal loss. Given its potential role in producing a toxic host microenvironment for transplanted donor stem cells, we investigated the interaction between Abeta and proliferation, survival, and differentiation of bone marrow-derived mesenchymal stem cells (BM-MSC) in culture. MATERIALS ANDMETHODS:
We used BM-MSC that had been isolated from mouse bone marrow and cultured, and we also assessed relevant reaction mechanisms using gene microarray, immunocytochemistry, and inhibitors of potential signalling molecules, such as mitogen-activated protein kinase (MAPK)/extracellular signal-regulated kinase (ERK)1/2 and tyrosine protein kinase. RESULTS ANDCONCLUSIONS:
Interestingly, we found that treatment with aggregated (1-40 or 1-42) and oligomeric (1-42) Abeta promoted neuronal-like differentiation of BM-MSC without toxic effects. This was not dependent on soluble factors released from BM-MSC progeny nor solely on formation of Abeta fibrils. The effect of Abeta is mediated by G-protein coupled receptors, neuropeptide Y1 (NPY1R) and serotonin (5-hydroxytryptamine) receptor 2B, via phosphatidylinositol-3-OH kinase-dependent activation of the MAPK/ERK1/2. Our results lend support to the idea that reciprocal donor stem cell-host interactions may promote a regenerative response that can be exploited by epigenetic modulation of NPY/serotonergic gene expression, for stem cell therapy, in Alzheimer's disease.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Peptide Fragments
/
Amyloid beta-Peptides
/
Receptors, Neuropeptide Y
/
MAP Kinase Signaling System
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Receptor, Serotonin, 5-HT2B
/
Mesenchymal Stem Cells
/
Neuronal Plasticity
Limits:
Animals
Language:
En
Journal:
Cell Prolif
Year:
2009
Document type:
Article
Affiliation country:
Corea del Sur