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Maternal Vitamin D prevents abnormal dopaminergic development and function in a mouse model of prenatal immune activation

Luan, Wei; Hammond, Luke Alexander; Vuillermot, Stephanie; Meyer, Urs; Eyles, Darryl Walter (2018). Maternal Vitamin D prevents abnormal dopaminergic development and function in a mouse model of prenatal immune activation. Scientific Reports, 8(1):9741.

Abstract

Dysfunction in dopamine (DA) systems is a prominent feature in schizophrenia patients and may result from the abnormal development of mesencephalic (mes)DA systems. Maternal immune activation (MIA) and developmental vitamin D (DVD)-deficiency both induce schizophrenia-relevant dopaminergic abnormalities in adult offspring. In this study, we investigated whether maternal administration of the vitamin D hormone (1,25OHD, VITD) could prevent MIA-induced abnormalities in DA-related behaviors and mesDA development. We administrated the viral mimetic polyriboinosinic-polyribocytidylic (poly (I:C)) simultaneously with 1,25OHD and/or their vehicles, to pregnant mouse dams at gestational day 9. Maternal treatment with VITD prevented MIA-induced hypersensitivity to acute DA stimulation induced by amphetamine, whereas it failed to block prepulse inhibition deficiency in MIA-exposed offspring. MIA and VITD both reduced fetal mesDA progenitor (Lmx1a + Sox2+) cells, while VITD treatment increased the number of mature (Nurr1 + TH+) mesDA neurons. Single-cell quantification of protein expression showed that VITD treatment increased the expression of Lmx1a, Nurr1 and TH in individual mesDA cells and restored normal mesDA positioning. Our data demonstrate that VITD prevents abnormal dopaminergic phenotypes in MIA offspring possibly via its early neuroprotective actions on fetal mesDA neurons. Maternal supplementation with the dietary form of vitamin D, cholecalciferol may become a valuable strategy for the prevention of MIA-induced neurodevelopmental abnormalities.

Additional indexing

Item Type:Journal Article, refereed, original work
Communities & Collections:04 Faculty of Medicine > Neuroscience Center Zurich
05 Vetsuisse Faculty > Veterinärwissenschaftliches Institut > Institute of Veterinary Pharmacology and Toxicology
Dewey Decimal Classification:570 Life sciences; biology
Scopus Subject Areas:Health Sciences > Multidisciplinary
Uncontrolled Keywords:Multidisciplinary
Language:English
Date:1 December 2018
Deposited On:24 Jan 2019 17:23
Last Modified:20 Oct 2024 01:40
Publisher:Nature Publishing Group
ISSN:2045-2322
OA Status:Gold
Free access at:PubMed ID. An embargo period may apply.
Publisher DOI:https://doi.org/10.1038/s41598-018-28090-w
PubMed ID:29950608
Project Information:
  • Funder: SNSF
  • Grant ID: 310030_169544
  • Project Title: Epigenetic and Transgenerational Mechanisms in Infection-Mediated Neurodevelopmental Disorders
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  • Language: English
  • Licence: Creative Commons: Attribution 4.0 International (CC BY 4.0)

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