Vitamin D treatment during pregnancy prevents autism-related phenotypes in a mouse model of maternal immune activation

Vuillermot, Stephanie, Luan, Wei, Meyer, Urs and Eyles, Darryl (2017) Vitamin D treatment during pregnancy prevents autism-related phenotypes in a mouse model of maternal immune activation. Molecular Autism, 8 1: . doi:10.1186/s13229-017-0125-0


Author Vuillermot, Stephanie
Luan, Wei
Meyer, Urs
Eyles, Darryl
Title Vitamin D treatment during pregnancy prevents autism-related phenotypes in a mouse model of maternal immune activation
Journal name Molecular Autism   Check publisher's open access policy
ISSN 2040-2392
Publication date 2017-03-07
Sub-type Article (original research)
DOI 10.1186/s13229-017-0125-0
Open Access Status DOI
Volume 8
Issue 1
Total pages 13
Place of publication London, United Kingdom
Publisher BioMed Central
Language eng
Formatted abstract
Background: Prenatal exposure to infection is a recognized environmental risk factor for neuropsychiatric disorders of developmental origins such as autism or schizophrenia. Experimental work in animals indicates that this link is mediated by maternal immune activation (MIA) involving interactions between cytokine-associated inflammatory events, oxidative stress, and other pathophysiological processes such as hypoferremia and zinc deficiency. Maternal administration of the viral mimic polyriboinosinic-polyribocytidylic acid (poly(I:C)) in mice produces several behavioral phenotypes in adult offspring of relevance to autism spectrum disorder (ASD) and other neurodevelopmental disorders.

Methods: Here, we investigated whether some of these phenotypes might also present in juveniles. In addition, given the known immunomodulatory and neuroprotective effects of vitamin D, we also investigated whether the co-administration of vitamin D could block MIA-induced ASD-related behaviors. We co-administered the hormonally active form of vitamin D, 1α,25 dihydroxy vitamin D3 (1,25OHD), simultaneously with poly(I:C) and examined (i) social interaction, stereotyped behavior, emotional learning and memory, and innate anxiety-like behavior in juveniles and (ii) the levels of the pro-inflammatory cytokines IL-1β, IL-6 and TNF-α in maternal plasma and fetal brains.

Results: We show that like adult offspring that were exposed to MIA, juveniles display similar deficits in social approach behavior. Juvenile MIA offspring also show abnormal stereotyped digging and impaired acquisition and expression of tone-cued fear conditioning. Importantly, our study reveals that prenatal administration of 1,25OHD abolishes all these behavioral deficits in poly(I:C)-treated juveniles. However, prenatal administration of vitamin D had no effect on pro-inflammatory cytokine levels in dams or in fetal brains suggesting the anti-inflammatory actions of vitamin D are not the critical mechanism for its preventive actions in this ASD animal model.

Conclusions: This work raises the possibility that early dietary supplementation with vitamin D may open new avenues for a successful attenuation or even prevention of neurodevelopmental disorders following maternal inflammation during pregnancy.
Keyword Autism
Cytokines
Dopamine
Maternal immune activation
Neurodevelopmental disorders
Schizophrenia
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
 
Versions
Version Filter Type
Citation counts: TR Web of Science Citation Count  Cited 0 times in Thomson Reuters Web of Science Article
Scopus Citation Count Cited 0 times in Scopus Article
Google Scholar Search Google Scholar
Created: Tue, 28 Mar 2017, 00:20:19 EST by Web Cron on behalf of Learning and Research Services (UQ Library)