Clinical Pharmacology & Biopharmaceutics
Open Access

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 demonstrate that incubation of AF-MSCs, obtained from 16-20 week pregnant women with 10 ng/ml bone morphogenetic protein (BMP)-9 for 48 hours in conditioned medium resulted in trans-differentiation to cholinergic neuronal-like cells. This phenomenon could also be obtained with N-benzylcinnamide (PT-3). Pre-treatment for 1 hour with 10 nM PT-3 augmented BMP-9 trans-differentiation 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 trans-differentiation 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 not provide a useful adjuvant in BMP-9-induced trans-differentiation of AFMSCs into ultimately cholinergic neurons.

Biography

Email: wipawan.tha@mahidol.ac.th