Developmental vitamin D (DVD) deficiency reduces Nurr1 and TH expression in post-mitotic dopamine neurons in rat mesencephalon

Luan, Wei, Hammond, Luke Alexander, Cotter, Edmund, Osborne, Geoffrey William, Alexander, Suzanne Adele, Nink, Virginia, Cui, Xiaoying and Eyles, Darryl Walter (2017) Developmental vitamin D (DVD) deficiency reduces Nurr1 and TH expression in post-mitotic dopamine neurons in rat mesencephalon. Molecular Neurobiology, 1-11. doi:10.1007/s12035-017-0497-3


Author Luan, Wei
Hammond, Luke Alexander
Cotter, Edmund
Osborne, Geoffrey William
Alexander, Suzanne Adele
Nink, Virginia
Cui, Xiaoying
Eyles, Darryl Walter
Title Developmental vitamin D (DVD) deficiency reduces Nurr1 and TH expression in post-mitotic dopamine neurons in rat mesencephalon
Journal name Molecular Neurobiology   Check publisher's open access policy
ISSN 1559-1182
0893-7648
Publication date 2017-04-01
Sub-type Article (original research)
DOI 10.1007/s12035-017-0497-3
Open Access Status Not yet assessed
Start page 1
End page 11
Total pages 11
Place of publication Heidelberg, Germany
Publisher Springer
Collection year 2018
Language eng
Abstract Developmental vitamin D (DVD) deficiency has been proposed as an important risk factor for schizophrenia. Our previous study using Sprague Dawley rats found that DVD deficiency disrupted the ontogeny of mesencephalic dopamine neurons by decreasing the mRNA level of a crucial differentiation factor of dopamine cells, the nuclear receptor related 1 protein (Nurr1). However, it remains unknown whether this reflects a reduction in dopamine cell number or in Nurr1 expression. It is also unclear if any particular subset of developing dopamine neurons in the mesencephalon is selectively affected. In this study, we employed state-of-the-art spinning disk confocal microscopy optimized for the imaging of tissue sections and 3D segmentation to assess post-mitotic dopamine cells on a single-cell basis in the rat mesencephalon at embryonic day 15. Our results showed that DVD deficiency did not alter the number, morphology, or positioning of post-mitotic dopamine cells. However, the ratio of Nurr1+TH+ cells in the substantia nigra pars compacta (SNc) compared with the ventral tegmental area (VTA) was increased in DVD-deficient embryos. In addition, the expression of Nurr1 in immature dopamine cells and mature dopamine neurons in the VTA was decreased in DVD-deficient group. Tyrosine hydroxylase was selectively reduced in SNc of DVD-deficient mesencephalon. We conclude that DVD deficiency induced early alterations in mesencephalic dopamine development may in part explain the abnormal dopamine-related behaviors found in this model. Our findings may have broader implications for how certain environmental risk factors for schizophrenia may shape the ontogeny of dopaminergic systems and by inference increase the risk of schizophrenia.
Keyword Dopamine
Mesencephalon
Nurr1
Schizophrenia
Tyrosine hydroxylase
Vitamin D
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
Australian Institute for Bioengineering and Nanotechnology Publications
 
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