Amyloid beta-derived neuroplasticity in bone marrow-derived mesenchymal stem cells is mediated by NPY and 5-HT2B receptors via ERK1/2 signalling pathways

H. K. Jin, J. S. Bae, S. Furuya, J. E. Carter

Research output: Contribution to journalArticlepeer-review

13 Citations (Scopus)

Abstract

Objective: In Alzheimer's disease, toxic soluble and insoluble forms of amyloid beta (Aβ) 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 Aβ and proliferation, survival, and differentiation of bone marrow-derived mesenchymal stem cells (BM-MSC) in culture. Materials and methods: 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 and conclusions: Interestingly, we found that treatment with aggregated (1-40 or 1-42) and oligomeric (1-42) Aβ 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 Aβ fibrils. The effect of Aβ 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.

Original languageEnglish
Pages (from-to)571-586
Number of pages16
JournalCell Proliferation
Volume42
Issue number5
DOIs
Publication statusPublished - Oct 2009

All Science Journal Classification (ASJC) codes

  • Cell Biology

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