title: Potential role of N-benzylcinnamide in inducing neuronal differentiation from human amniotic fluid mesenchymal stem cells.
abstract: Neurodegenerative disorders are characterized by chronic and progressive loss of neurons in structure and function related to aging, such as Alzheimer's disease, the latter characterized by the degeneration of cholinergic neurons in basal forebrain connected to the cerebral cortex and hippocampus. Amniotic fluid mesenchymal stem cells (AF-MSCs) have been proposed as one of the candidates for stem cell therapy of nervous system disorders. This study demonstrates that incubation of AF-MSCs, obtained from 16 to 20 week pregnant women, with 10ng/ml bone morphogenetic protein (BMP)-9 for 48h in conditioned medium resulted in transdifferentiation to cholinergic neuronal-like cells. This phenomenon could also be obtained with N-benzylcinnamide (PT-3). Pre-treatment for 1h with 10nM PT-3 augmented BMP-9 transdifferentiation effect, elevated βIII-tubulin cell numbers and fluorescence intensity of immunoreactive ChAT, ameliorated BMP-9-related production of reactive oxygen species and enhanced anti-apoptosis status of the neuronal-like cells. The transdiffirentiation process was accompanied by increased p53 but decreased Notch1 and SIRT1 (p53 deacetylase) levels, and activation of p38, ERK1/2 MAPK, and PI3K/Akt pathways, in concert with inactivation of JNK, all of which were accentuated by PT-3 pre-treatment. These findings suggest that N-benzylcinnamide may provide a useful adjuvant in BMP-9-induced transdifferentiation of AFMSCs into ultimately cholinergic neurons.
authors.affiliation: Research Center for Neuroscience, Institute of Molecular Biosciences, Mahidol University, Salaya, Nakhonpathom, Thailand. Electronic address: wipawan.tha@mahidol.ac.th.
authors.forename: Wipawan
authors.initials: W
authors.lastname: Thangnipon
authors.affiliation: Research Center for Neuroscience, Institute of Molecular Biosciences, Mahidol University, Salaya, Nakhonpathom, Thailand.
authors.forename: Nicha
authors.initials: N
authors.lastname: Puangmalai
authors.affiliation: Research Center for Neuroscience, Institute of Molecular Biosciences, Mahidol University, Salaya, Nakhonpathom, Thailand; Department of Companion Animal Clinical Sciences, Faculty of Veterinary Medicine, Kasetsart University, Kamphaeng Saen, Nakhonpathom, Thailand.
authors.forename: Nirut
authors.initials: N
authors.lastname: Suwanna
authors.affiliation: Department of Biochemistry, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand.
authors.forename: Rungtip
authors.initials: R
authors.lastname: Soi-Ampornkul
authors.affiliation: Research Center for Neuroscience, Institute of Molecular Biosciences, Mahidol University, Salaya, Nakhonpathom, Thailand.
authors.forename: Ruchee
authors.initials: R
authors.lastname: Phonchai
authors.affiliation: Research Center for Neuroscience, Institute of Molecular Biosciences, Mahidol University, Salaya, Nakhonpathom, Thailand.
authors.forename: Naiphinich
authors.initials: N
authors.lastname: Kotchabhakdi
authors.affiliation: Research Center for Neuroscience, Institute of Molecular Biosciences, Mahidol University, Salaya, Nakhonpathom, Thailand.
authors.forename: Sujira
authors.initials: S
authors.lastname: Mukda
authors.affiliation: Stem Cell Research and Development Unit, Department of Obstetrics and Gynecology, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand.
authors.forename: Tatsanee
authors.initials: T
authors.lastname: Phermthai
authors.affiliation: Stem Cell Research and Development Unit, Department of Obstetrics and Gynecology, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand.
authors.forename: Suphakde
authors.initials: S
authors.lastname: Julavijitphong
authors.affiliation: Department of Chemistry, Faculty of Science, Mahidol University, Bangkok, Thailand.
authors.forename: Patoomratana
authors.initials: P
authors.lastname: Tuchinda
authors.affiliation: Nakhonsawan Campus, Mahidol University, Amphoe Phayuhakiri, Nakhonsawan, Thailand.
authors.forename: Saksit
authors.initials: S
authors.lastname: Nobsathian
mesh_terms: D000653:Amniotic Fluid / Q000166:cytology*; D054338:Cell Transdifferentiation; D002795:Choline O-Acetyltransferase / Q000378:metabolism; D059329:Cholinergic Neurons / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D002934:Cinnamates / Q000494:pharmacology*; D004347:Drug Interactions; D004789:Enzyme Activation; D005260:Female; D055427:Growth Differentiation Factor 2 / Q000494:pharmacology; D006801:Humans; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D051881:Receptor, Notch1 / Q000378:metabolism; D056564:Sirtuin 1 / Q000378:metabolism; D014404:Tubulin / Q000378:metabolism; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism
chemical_list: D002934:Cinnamates; D055427:Growth Differentiation Factor 2; C586180:N-benzylcinnamide; D051881:Receptor, Notch1; C498585:TUBB3 protein, human; D014404:Tubulin; D016159:Tumor Suppressor Protein p53; D002795:Choline O-Acetyltransferase; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; C447939:SIRT1 protein, human; D056564:Sirtuin 1
keywords: Alzheimer’s disease; Antioxidant; Cholinergic neuron; Differentiation; Mechanism; N-Benzylcinnamide