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 Alzheimerâ��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 �²III-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