Maternal immune activation: Implications for neuropsychiatric disorders

Estes, Myka L.; McAllister, A. Kimberley

doi:10.1126/science.aag3194

Cited by 912 publications

(906 citation statements)

References 89 publications

(174 reference statements)

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“…Moreover, considering the anti-inflammatory properties of OT, ELS-associated deficiencies in OT signaling could favor a pro-inflammatory phenotype in pregnant women. Evidence from animal studies and epidemiological data suggest that in utero exposure to higher levels of pro-inflammatory cytokines may alter fetal brain development and is associated with higher risk for neurodevelopmental disorders such as autism or schizophrenia (Estes and McAllister, 2016). …”

Section: Ot Pathways In the Intergenerational Transmission Of Matementioning

confidence: 99%

Oxytocin pathways in the intergenerational transmission of maternal early life stress

Toepfer

Heim

Entringer

et al. 2017

Neuroscience & Biobehavioral Reviews

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Severe stress in early life, such as childhood abuse and neglect, constitutes a major risk factor in the etiology of psychiatric disorders and somatic diseases. Importantly, these long-term effects may impact the next generation. The intergenerational transmission of maternal early life stress (ELS) may occur via pre-and postnatal pathways, such as alterations in maternal-fetal-placental stress physiology, maternal depression during pregnancy and postpartum, as well as impaired mother-offspring interactions. The neuropeptide oxytocin (OT) has gained considerable attention for its role in modulating all of these assumed transmission pathways. Moreover, central and peripheral OT signaling pathways are highly sensitive to environmental exposures and may be compromised by ELS with implications for these putative transmission mechanisms. Together, these data suggest that OT pathways play an important role in the intergenerational transmission of maternal ELS in humans. By integrating recent studies on gene-environment interactions and epigenetic modifications in OT pathway genes, the present review aims to develop a conceptual framework of intergenerational transmission of maternal ELS that emphasizes the role of OT.

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Section: Ot Pathways In the Intergenerational Transmission Of Matementioning

confidence: 99%

Oxytocin pathways in the intergenerational transmission of maternal early life stress

Toepfer

Heim

Entringer

et al. 2017

Neuroscience & Biobehavioral Reviews

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“…Moreover, animal model research suggests that maternal immune activation (MIA), even without exposure to infectious pathogens, can cause behavioral and histological phenotypes of ASD in offspring 12. The prenatal administration of polyriboinosinic:polyribocytidylic acid (poly[I:C]) is one of the most widely used methods for generating an MIA model in mice.…”

Section: Introductionmentioning

confidence: 99%

Maternal immune activation alters brain microRNA expression in mouse offspring

Sunwoo

Jeon²,

Moon

et al. 2018

Ann Clin Transl Neurol

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ObjectiveMaternal immune activation (MIA) is associated with an increased risk of autism spectrum disorder (ASD) in offspring. Herein, we investigate the altered expression of microRNAs (miRNA), and that of their target genes, in the brains of MIA mouse offspring.MethodsTo generate MIA model mice, pregnant mice were injected with polyriboinosinic:polyribocytidylic acid on embryonic day 12.5. We performed miRNA microarray and mRNA sequencing in order to determine the differential expression of miRNA and mRNA between MIA mice and controls, at 3 weeks of age. We further identified predicted target genes of dysregulated miRNAs, and miRNA‐target interactions, based on the inverse correlation of their expression levels.ResultsMice prenatally subjected to MIA exhibited behavioral abnormalities typical of ASD, such as a lack of preference for social novelty and reduced prepulse inhibition. We found 29 differentially expressed miRNAs (8 upregulated and 21 downregulated) and 758 differentially expressed mRNAs (542 upregulated and 216 downregulated) in MIA offspring compared to controls. Based on expression levels of the predicted target genes, 18 downregulated miRNAs (340 target genes) and three upregulated miRNAs (60 target genes) were found to be significantly enriched among the differentially expressed genes. miRNA and target gene interactions were most significant between mmu‐miR‐466i‐3p and Hfm1 (ATP‐dependent DNA helicase homolog), and between mmu‐miR‐877‐3p and Aqp6 (aquaporin 6).InterpretationOur results provide novel information regarding miRNA expression changes and their putative targets in the early postnatal period of brain development. Further studies will be needed to evaluate potential pathogenic roles of the dysregulated miRNAs.

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“…This is partly due to the high prevalence of co-morbid conditions that are associated with immune mediated inflammation in ASD subjects, and convincing evidence indicating a role of maternal inflammation in ASD [1,2]. In animal models of ASD, mothers who were induced to have inflammation during mid-gestation, had offspring that developed ASD symptoms after birth.…”

Section: Introductionmentioning

confidence: 99%