Vitamin D signaling and the differentiation of developing dopamine systems

Pertile, Renata A. N., Cui, Xiaoying and Eyles, Darryl W. (2016) Vitamin D signaling and the differentiation of developing dopamine systems. Neuroscience, 333 193-203. doi:10.1016/j.neuroscience.2016.07.020

Author Pertile, Renata A. N.
Cui, Xiaoying
Eyles, Darryl W.
Title Vitamin D signaling and the differentiation of developing dopamine systems
Journal name Neuroscience   Check publisher's open access policy
ISSN 1873-7544
Publication date 2016-10-01
Sub-type Article (original research)
DOI 10.1016/j.neuroscience.2016.07.020
Open Access Status Not yet assessed
Volume 333
Start page 193
End page 203
Total pages 11
Place of publication Kidlington, Oxford, United Kingdom
Publisher Pergamon Press
Language eng
Formatted abstract
Vitamin D regulates multiple factors including those involved in the ontogeny of dopaminergic systems. It has been shown that in neonatal rats maternally deprived of vitamin D, dopamine (DA) turnover is decreased with associated reductions in one catabolic enzyme, catechol-o-methyl transferase (COMT). To directly examine this signaling relationship, in the present study we have over-expressed the vitamin D receptor (VDR) in neuroblastoma SH-SY5Y cells in order to examine the mechanisms by which the active vitamin D hormone, 1,25(OH)2D3, via its receptor VDR, affects DA production and turnover. Our results show that VDR overexpression increases DA neuron differentiation by increasing tyrosine hydroxylase expression, DA production and decreasing the expression of NEUROG2 a marker of immature DA neurons. In the VDR-overexpressing cells, 1,25(OH)2D3 further increased the levels of the DA-metabolites 3-MT and HVA and elevated COMT gene expression. Chromatin immunoprecipitation revealed that 1,25(OH)2D3 increased VDR binding in three regions of the COMT promoter, strongly suggesting direct regulation. In addition, 1,25(OH)2D3 treatment attenuated increased levels of MAOA, DRD2 and VMAT2 gene expression caused by the VDR-overexpression. Taken together, these results show VDR and 1,25(OH)2D3 are directly involved in regulating the expression of dopaminergic-associated genes and that this in vitro neuronal model is a useful tool for identifying the role of 1,25(OH)2D3 in DA neuronal development and maturation.
Keyword COMT
Vitamin D receptor (VDR)
Vitamin D,1,25(OH)2D3
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: HERDC Pre-Audit
Queensland Brain Institute Publications
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