The influence of immune activation at early vs late gestation on fetal NRG1-ErbB4 expression and behavior in juvenile and adult mice offspring

Dabbah-Assadi, Fadwa; Alon, David; Golani, Idit; Doron, Ravid; Kremer, I; Beloosesky, Ron; Shamir, Alon

doi:10.1016/j.bbi.2019.02.002

Cited by 20 publications

(20 citation statements)

References 32 publications

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“…Likewise, Esnafoglu 92 suggested that NRG1-ErbB signal system may contribute to the disorder, and Dabbah-Assadi et al 93 suggested that NRG1-ErbB4 pathway disruption can lead to cognitive dysfunction. While NRG2 and NRG3 complexes have not been linked to ASD, many reports support their link to other neurodevelopmental disorders such as SCZ and bipolar disorder 94,95 .…”

Section: Discussionmentioning

confidence: 99%

Characterization of Cell-cell Communication in Autistic Brains with Single Cell Transcriptomes

Astorkia

Lachman

Zheng

2021

Preprint

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Autism spectrum disorder is a neurodevelopmental disorder, affecting 1-2% of children. Studies have revealed genetic and cellular abnormalities in the brains of affected individuals, leading to both regional and distal cell communication deficits. Recent application of single cell technologies, especially single cell transcriptomics, has significantly expanded our understanding of brain cell heterogeneity and further demonstrated that multiple cell types and brain layers or regions are perturbed in autism. The underlying high-dimensional single cell data provides opportunities for multi-level computational analysis that collectively can better deconvolute the molecular and cellular events altered in autism. Here, we apply advanced computation and pattern recognition approaches on single cell RNA-seq data to infer and compare inter-cell-type signaling communications in autism brains and controls. Our results indicate that at a global level there are cell-cell communication differences in autism in comparison to controls, largely involving neurons as both signaling senders and receivers, but glia also contribute to the communication disruption. Although the magnitude of change is moderate, we find that excitatory and inhibitor neurons are involved in multiple intercellular signaling that exhibit increased strengths in autism, such as NRXN and CNTN signaling. Not all genes in the intercellular signaling pathways are differentially expressed, but genes in the pathways are enriched for axon guidance, synapse organization, neuron migration, and other critical cellular functions. Furthermore, those genes are highly connected to and enriched for genes previously associated with autism risks. Overall, our proof-of-principle computational study using single cell data uncovers key intercellular signaling pathways that are potentially disrupted in the autism brains, suggesting that more studies examining cross-cell type affects can be valuable for understanding autism pathogenesis.

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Section: Discussionmentioning

confidence: 99%

Characterization of Cell-cell Communication in Autistic Brains with Single Cell Transcriptomes

Astorkia

Lachman

Zheng

2021

Preprint

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“…Infection triggers proinflammatory cytokines and microglial activation in the brain and can affect mood, cognition, and behavior (59, 65). Accumulating evidence suggests that prenatal and postnatal immunostimulation influences neurogenesis, cognitive function, and behavior in offspring (67–74). This study raises the potential specter of permanent behavioral changes caused by nHSV in babies born to mothers without preexisting immunity.…”

Section: Discussionmentioning

confidence: 99%

Maternal immunization confers protection against neonatal herpes simplex mortality and behavioral morbidity

et al. 2019

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Neonatal herpes simplex virus (nHSV) infections cause devastating morbidity and mortality in infants.Most nHSV cases are associated with primary maternal infection, consistent with the hypothesis that maternal immunity is protective. In humans, we found HSV-specific neutralizing antibodies in newborns of immune mothers, indicating that placentally transferred HSV-specific antibody is protective. Using a murine model, we showed that passive administration of HSV-specific antibody to dams prevented disseminated infection and mortality in pups. Maternal immunization with an HSV-2 replication-defective vaccine candidate, dl5–29, led to transfer of HSV-specific antibodies into neonatal circulation that protected against nHSV neurological disease and death. Furthermore, we observed considerable anxiety-like behavior in adult mice that had been infected with low doses of HSV as neonates, despite a notable lack of signs of infection. This phenotype suggests that nHSV infection can have an unsuspected and permanent impact on behavior. These behavioral sequelae of nHSV were prevented by maternal immunization with dl5–29, demonstrating an unexpected benefit of immunization. These findings also support the general concept that maternal immunization can prevent neurotropic neonatal infections and associated morbidity and mortality.

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“…However, anti-inflammatory gene and protein expression was decreased in male offspring, while increased in female offspring (64). Debbah-Assadi et al reported sex-specific and time related behavioral changes for Poly I:C MIA exposed offspring (68). Exposure to MIA in late gestation resulted in a lack of preference to novel objects in female adult offspring, while alterations in working memory were observed in male adult offspring (68).…”

Section: Consequences Of Poly I:c For Adult Life -mentioning

confidence: 99%

LPS versus Poly I:C model: comparison of long-term effects of bacterial and viral maternal immune activation on the offspring

Bao

Hofsink

Plösch

2022

American Journal of Physiology-Regulatory, Integrative and Comp

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A prominent health issue nowadays is the COVID-19 pandemic, which poses acute risks to human health. However, the long-term health consequences are largely unknown and cannot be neglected. An especially vulnerable period for infection is pregnancy, when infections could have long-term health effect on the child. Evidence suggests that maternal immune activation (MIA) induced by either bacteria or viruses presents various effects on the offspring, leading to adverse phenotypes in many organ systems. This review compares the mechanisms of bacterial and viral MIA and the possible long-term outcomes for the offspring by summarizing the outcome in animal LPS and Poly I:C models. Both models are activated immune responses mediated by Toll-like receptors. The outcomes for MIA offspring include neurodevelopment, immune response, circulation, metabolism and reproduction. Some of these changes keep existing until later life. Besides different doses and batches of LPS and Poly I:C, the injection day, administration route and also different animal species influence the outcomes. Here, we specifically aim to support colleagues when choosing their animal models for future studies.

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The influence of immune activation at early vs late gestation on fetal NRG1-ErbB4 expression and behavior in juvenile and adult mice offspring

Cited by 20 publications

References 32 publications

Characterization of Cell-cell Communication in Autistic Brains with Single Cell Transcriptomes

Characterization of Cell-cell Communication in Autistic Brains with Single Cell Transcriptomes

Maternal immunization confers protection against neonatal herpes simplex mortality and behavioral morbidity

LPS versus Poly I:C model: comparison of long-term effects of bacterial and viral maternal immune activation on the offspring

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