Ferulic Acid Induces NURR1 Expression and Promotes DopaminergicDifferentiation in Neural Precursor Cells

Document Type : Original Article

Authors
1 Department of Biology, ACECR Institute of Higher Education, Isfahan, Iran
2 Department of Animal Biotechnology, Cell Science Research Center, Royan Institute for Biotechnology, ACECR, Isfahan, Iran.
3 Department of Animal Biotechnology, Cell Science Research Center, Royan Institute for Biotechnology, ACECR, Isfahan, Iran
Abstract
Degeneration of dopaminergic (DA) neurons in the substantia nigra is known as the main cause
of Parkinson's disease (PD). Preventing the loss of DA neurons alongside the cell
-replacement
therapy have brought tremendous hope for the treatment of PD. For this purpose, various studies
have been done to find the specific DA neuro
-protective compounds or progressing DA
-
differentiation methods. Ferulic acid (FA) has strong neuro
-protective effects, but at this point its
role on protection and differentiation of DA neurons is not well
-defined. Mouse neural stem cells
(mNSCs) were treated with FA and expressions of TH (tyrosine hydroxylase) and NURR1 as the
DA neuron specific markers were determined using real time qRT
-PCR and immunostaining
assays. Finally, efficacy of FA on DA differentiation was evaluated in comparison with other
methods using fibroblast growth factor 8b (FGF8b) and sonic hedgehog (SHH). Treatment with
FA could increase the Th and Nurr1 gene expressions in mNSCs. Also, it enhanced
β
-tubullin
-III
expression and increased the neurite length in treated groups. Real time qRT
-PCR and
immunostaining assays showed that FA could increase DA differentiation in mNSCs effectively.
Also, gene expression profile in some groups showed that FA can raise the differentiation rate of
other neuronal subtypes such as cholinergic neurons. FA effectively induces the DA
differentiation in neural precursor cells by its ability to increase the expression of the NURR1
transcription factor, which is a known transcription factor for differentiation of midbrain DA
neurons.