Maternal vitamin D deficiency alters fetal brain development in the BALB/c mouse

Hawes, Jazmin E.; Tesic, Dijana; Whitehouse, Andrew J. O.; Zosky, Graeme R.; Smith, Jeremy Troy; Wyrwoll, Caitlin

doi:10.1016/j.bbr.2015.03.008

Cited by 92 publications

(88 citation statements)

References 45 publications

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“…At earlier developmental stages, DVD-deficient embryos display a reduced expression of the crucial dopamine specification factors, Nurr1 and p57kip2, in mesencephalon . Finally DVD-deficiency has also very recently been shown to down-regulate TH gene and protein expression in the embryonic brains of female mice (Hawes et al, 2015). In summary, these findings strongly suggest that vitamin D modulates the orderly early development of dopaminergic systems.…”

Section: Introductionmentioning

confidence: 91%

Vitamin D regulates tyrosine hydroxylase expression: N-cadherin a possible mediator

et al. 2015

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Vitamin D is a neuroactive steroid. Its genomic actions are mediated via the active form of vitamin D, 1,25(OH)2D3, binding to the vitamin D receptor (VDR). The VDR emerges in the rat mesencephalon at embryonic day 12, representing the peak period of dopaminergic cell birth. Our prior studies reveal that developmental vitamin D (DVD)-deficiency alters the ontogeny of dopaminergic neurons in the developing mesencephalon. There is also consistent evidence from others that 1,25(OH)2D3 promotes the survival of dopaminergic neurons in models of dopaminergic toxicity. In both developmental and toxicological studies it has been proposed that 1,25(OH)2D3 may modulate the differentiation and maturation of dopaminergic neurons; however, to date there is lack of direct evidence. The aim of the current study is to investigate this both in vitro using a human SH-SY5Y cell line transfected with rodent VDR and in vivo using a DVD-deficient model. Here we show that in VDR-expressing SH-SY5Y cells, 1,25(OH)2D3 significantly increased production of tyrosine hydroxylase (TH), the rate-limiting enzyme in dopamine synthesis. This effect was dose- and time-dependent, but was not due to an increase in TH-positive cell number, nor was it due to the production of trophic survival factors for dopamine neurons such as glial-derived neurotrophic factor (GDNF). In accordance with 1,25(OH)2D3's anti-proliferative actions in the brain, 1,25(OH)2D3 reduced the percentage of dividing cells from approximately 15-10%. Given the recently reported role of N-cadherin in the direct differentiation of dopaminergic neurons, we examined here whether it may be elevated by 1,25(OH)2D3. We confirmed this in vitro and more importantly, we showed DVD-deficiency decreases N-cadherin expression in the embryonic mesencephalon. In summary, in our in vitro model we have shown 1,25(OH)2D3 increases TH expression, decreases proliferation and elevates N-cadherin, a potential factor that mediates these processes. Accordingly all of these findings are reversed in the developing brain in our DVD-deficiency model. Remarkably our findings in the DVD-deficiency model phenocopy those found in a recent model where N-cadherin was regionally ablated from the mesencephalon. This study has, for the first time, shown that vitamin D directly modulates TH expression and strongly suggests N-cadherin may be a plausible mediator of this process both in vitro and in vivo. Our findings may help to explain epidemiological data linking DVD deficiency with schizophrenia.

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Section: Introductionmentioning

confidence: 91%

Vitamin D regulates tyrosine hydroxylase expression: N-cadherin a possible mediator

et al. 2015

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“…In adult life, these rats tend to demonstrate subtle alterations in learning and memory and impaired attentional processing [81]. Prenatal VDD induces similar alterations in fetal mouse brain morphology and mouse behavior [83,84]. Notably, it has been reported that maternal 1,25(OH) 2 D 3 insufficiency during pregnancy in humans is also significantly associated with offspring's language impairment [85].…”

Section: Vitamin D In Nervous System Physiology Neuroprotection Andmentioning

confidence: 95%

Vitamin D and Sphingolipids: Role in Bone and Neural System

Frati¹,

Gil²,

Pierucci³

et al. 2017

A Critical Evaluation of Vitamin D - Basic Overview

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Abstract1-Alpha,25-dihydroxyvitamin D3 (1,25(OH) 2 D 3 ) is known to play an important physiological role on growth and differentiation in a variety of nonmalignant and malignant cell types through classical actions, mediated by its specific receptor (VDR), and nongenomic actions resulting in the activation of specific signalling pathways. Due to the broad distribution of Vitamin D Receptor (VDR) in many tissues and the ability of 1,25(OH) 2 D 3 to regulate fundamental processes, such as cell proliferation and differentiation, this steroid hormone has been suggested in the treatment of different diseases, from cancer to neurodegenerative diseases. In fact, structural 1,25(OH) 2 D 3 analogues, with weaker collateral effects, have recently entered in clinical trials. Other interesting molecules due to their pleiotropic actions are the bioactive sphingolipids (SLs), in particular ceramide (Cer) and sphingosine 1-phosphate (S1P). Cells maintain a dynamic balance of these metabolites since Cer and sphingoid bases mediate cell death, while S1P exerts mitogenic effects and promotes differentiation of several cell types including osteogenic and neural cells. The biological actions of 1,25(OH) 2 D 3 and SLs, in particular S1P, share many common effectors, including calcium regulation, growth factor expression, inflammatory cytokines, etc., but whether they could act synergistically is still unknown and deserves further investigation.

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“…(24) " (D) In the discussion section, "That prenatal vitamin D-deficiency leads to alterations in fetal mouse brain morphology and genes related to neuronal survival, speech and language development, and dopamine synthesis. (32) " (E) In the discussion section, "Findings were consistent with maternal vitamin D deficiency's being a risk factor for (IAD), possibly by affecting fetal brain development as well as possibly by affecting maternal immune system status during pregnancy. (33) " (F) In the discussion section, "Evidence that vitamin D hormone (calcitriol) activates the transcription of the serotonin-synthesizing gene tryptophan hydroxylase 2 (TPH2) in the brain at a vitamin D response element (VDRE) and represses the transcription of TPH1 in tissues outside the blood-brain barrier at a distinct VDRE.…”

mentioning

confidence: 88%

Erratum Re: Relationship Between Neonatal Vitamin D at Birth and Risk of Autism Spectrum Disorders: the NBSIB Study

2018

Journal of Bone and Mineral Research

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Maternal vitamin D deficiency alters fetal brain development in the BALB/c mouse

Cited by 92 publications

References 45 publications

Vitamin D regulates tyrosine hydroxylase expression: N-cadherin a possible mediator

Vitamin D regulates tyrosine hydroxylase expression: N-cadherin a possible mediator

Vitamin D and Sphingolipids: Role in Bone and Neural System

Erratum Re: Relationship Between Neonatal Vitamin D at Birth and Risk of Autism Spectrum Disorders: the NBSIB Study

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