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

研究成果: Contribution to journalArticle査読

15 被引用数 (Scopus)

抄録

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.

本文言語英語
ページ(範囲)571-586
ページ数16
ジャーナルCell Proliferation
42
5
DOI
出版ステータス出版済み - 10 2009

All Science Journal Classification (ASJC) codes

  • 細胞生物学

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