title: Amyloid beta-derived neuroplasticity in bone marrow-derived mesenchymal stem cells is mediated by NPY and 5-HT2B receptors via ERK1/2 signalling pathways.
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.
  
  
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Laboratory Animal Medicine, College of Veterinary Medicine, Kyungpook National University, Jung-Gu, Daegu, South Korea.
authors.forename: H K
authors.initials: HK
authors.lastname: Jin
authors.forename: J S
authors.initials: JS
authors.lastname: Bae
authors.forename: S
authors.initials: S
authors.lastname: Furuya
authors.forename: J E
authors.initials: JE
authors.lastname: Carter
mesh_terms: D000544:Alzheimer Disease / Q000378:metabolism / Q000473:pathology; D016229:Amyloid beta-Peptides / Q000378:metabolism* / Q000494:pharmacology; D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology; D001854:Bone Marrow Cells / Q000166:cytology / Q000378:metabolism; D002454:Cell Differentiation / Q000187:drug effects / Q000502:physiology; D002455:Cell Division / Q000187:drug effects / Q000502:physiology; D002470:Cell Survival / Q000187:drug effects / Q000502:physiology; D002478:Cells, Cultured; D034281:Dynamins / Q000378:metabolism; D020935:MAP Kinase Signaling System / Q000502:physiology*; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism; D009473:Neuronal Plasticity / Q000502:physiology*; D009478:Neuropeptide Y / Q000235:genetics / Q000378:metabolism; D010446:Peptide Fragments / Q000378:metabolism* / Q000494:pharmacology; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D044403:Receptor, Serotonin, 5-HT2B / Q000378:metabolism*; D017476:Receptors, Neuropeptide Y / Q000378:metabolism*
chemical_list: D016229:Amyloid beta-Peptides; D009478:Neuropeptide Y; D010446:Peptide Fragments; D044403:Receptor, Serotonin, 5-HT2B; D017476:Receptors, Neuropeptide Y; C078592:amyloid beta-protein (1-40); C075222:amyloid beta-protein (1-42); C097212:neuropeptide Y-Y1 receptor; D019869:Phosphatidylinositol 3-Kinases; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D034281:Dynamins