scholarly journals Enhancing rigor and reproducibility in maternal immune activation models: practical considerations and predicting resilience and susceptibility using baseline immune responsiveness before pregnancy

2019 ◽  
Author(s):  
Myka L. Estes ◽  
Kathleen Farrelly ◽  
Scott Cameron ◽  
John Paul Aboubechara ◽  
Lori Haapanen ◽  
...  
Keyword(s):  
Immune Responses ◽  
Immune Activation ◽  
Therapeutic Interventions ◽  
Poly I:C ◽  
Immune Responsiveness ◽  
Rodent Models ◽  
Maternal Infection ◽  
Scientific Rigor ◽  
Maternal Immune Activation ◽  
New Biomarkers

AbstractDespite the potential of rodent models of maternal immune activation (MIA) to identify new biomarkers and therapeutic interventions for a range of psychiatric disorders, their value is currently limited by issues of scientific rigor and reproducibility. Here, we report three sources of variability—the immunogenicity of the poly(I:C), the baseline immune responsiveness (BIR) of the females prior to pregnancy, and differences in immune responses in C57/B6 dams across vendors. Similar to the variable effects of human maternal infection, MIA in mice does not cause disease-related phenotypes in all offspring and the magnitude and type of maternal response, determined by a combination of poly(I:C) dose and BIR, predicts offspring outcome. Together, our results provide recommendations for optimization of MIA protocols to enhance rigor and reproducibility and reveal new factors that drive susceptibility of some pregnancies and resilience of others to MIA-induced abnormalities in offspring.

Influence of poly(I:C) variability on thermoregulation, immune responses and pregnancy outcomes in mouse models of maternal immune activation

2019 ◽  
Vol 80 ◽  
pp. 406-418 ◽  
Author(s):  
Flavia S. Mueller ◽  
Juliet Richetto ◽  
Lindsay N. Hayes ◽  
Alice Zambon ◽  
Daniela D. Pollak ◽  
...  
Keyword(s):  
Immune Responses ◽  
Mouse Models ◽  
Immune Activation ◽  
Pregnancy Outcomes ◽  
Poly I:C ◽  
Maternal Immune Activation

scholarly journals The Effect of Maternal Immune Activation on Social Play-Induced Ultrasonic Vocalization in Rats

2021 ◽  
Vol 11 (3) ◽  
pp. 344
Author(s):  
Kinga Gzielo ◽  
Agnieszka Potasiewicz ◽  
Ewa Litwa ◽  
Diana Piotrowska ◽  
Piotr Popik ◽  
...  
Keyword(s):  
Immune Activation ◽  
Social Play ◽  
Autism Spectrum ◽  
Repetitive Behaviors ◽  
Male Rats ◽  
Poly I:C ◽  
Maternal Immune Activation ◽  
Increased Risk ◽  
Adolescent Rats ◽  
The Impact

Prenatal maternal infection is associated with an increased risk of various neurodevelopmental disorders, including autism spectrum disorders (ASD). Maternal immune activation (MIA) can be experimentally induced by prenatal administration of polyinosinic:polycytidylic acid (poly I:C), a synthetic viral-like double-stranded RNA. Although this MIA model is adopted in many studies, social and communicative deficits, included in the first diagnostic criterion of ASD, are poorly described in the offspring of poly(I:C)-exposed dams. This study aimed to characterize the impact of prenatal poly(I:C) exposure on socio-communicative behaviors in adolescent rats. For this purpose, social play behavior was assessed in both males and females. We also analyzed quantitative and structural changes in ultrasonic vocalizations (USVs) emitted by rats during the play test. Deficits of social play behaviors were evident only in male rats. Males also emitted a significantly decreased number of USVs during social encounters. Prenatal poly(I:C) exposure also affected acoustic call parameters, as reflected by the increased peak frequencies. Additionally, repetitive behaviors were demonstrated in autistic-like animals regardless of sex. This study demonstrates that prenatal poly(I:C) exposure impairs socio-communicative functioning in adolescent rats. USVs may be a useful tool for identifying early autistic-like abnormalities.

scholarly journals Neurodevelopmental Disorders Induced by Maternal Immune Activation: Toward a Prevention Strategy in the Era of the COVID-19 Pandemic

2020 ◽  
Vol 1 (1) ◽  
pp. 24-26
Author(s):  
Kazuhiro Sakurada ◽  
Yoshihiro Noda
Keyword(s):  
Immune Activation ◽  
Neurodevelopmental Disorders ◽  
Data Science ◽  
Biological Effects ◽  
Global Scale ◽  
Maternal Infection ◽  
Public Health Perspective ◽  
Daily Lives ◽  
Maternal Immune Activation ◽  
The Impact

As of summer 2020, the COVID-19 pandemic is having a major impact on our daily lives on a global scale, forcing us to change to the new normal. However, the effects are not only detrimental to our present socioeconomic conditions but also have the risk of having negative biological effects on our descendants. Of concern is the effect of maternal immune activation following maternal infection with COVID-19 on the fetus’ cerebral nervous system. While we are currently occupied with countering the imminent threats in front of us, we also need to take steps from a public health perspective to reduce the impact of maternal infection on the fetus, especially the risk of neurodevelopmental disorders. However, such a risk can be prevented and managed through the digital transformation of the nation’s health data and the strategic application of sophisticated data science approaches to those big data.

scholarly journals Integration of behavioral and biological variables using penalized regression: an application to the maternal immune activation model of autism

2020 ◽  
Author(s):  
Cristina Paraschivescu ◽  
Susana Barbosa ◽  
Thomas Lorivel ◽  
Nicolas Glaichenhaus ◽  
Laetitia Davidovic
Keyword(s):  
Immune Activation ◽  
Animal Studies ◽  
Penalized Regression ◽  
Autism Spectrum ◽  
Individual Variability ◽  
Poly I:C ◽  
Maternal Immune Activation ◽  
Biological Variables ◽  
Underlying Mechanisms ◽  
New Variables

AbstractMaternal immune activation (MIA) during pregnancy increases the odds of developing neuropsychiatric disorders such as autism spectrum disorder (ASD) later in life. In pregnant mice, MIA can be induced by injecting the viral mimic polyinosinic:polycytidylic acid (poly(I:C) to pregnant dams resulting in altered fetal neurodevelopmental and behavioral changes in their progeny. Although the murine MIA model has been extensively studied worldwide, the underlying mechanisms have only been partially elucidated. Furthermore, the murine MIA model suffers from lack of reproducibility, at least in part because it is highly influenced by subtle changes in environmental conditions. In human studies, multivariable (MV) statistical analysis is widely used to control for covariates including sex, age, exposure to environmental factors and many others. We reasoned that animal studies in general, and studies on the MIA model in particular, could therefore benefit from MV analyzes to account for complex phenotype interactions and high inter-individual variability. Here, we used a dataset consisting of 26 variables collected on 67 male pups during the course of several independent experiments on the MIA model. We then analyzed this dataset using penalized regression to identify variables associated with in utero exposure to MIA. In addition to confirming the association between some previously described biological variables and MIA, we identified new variables that could play a role in neurodevelopment alterations. Aside from providing new insights into variable interactions in the MIA model, this study highlights the importance of extending the use of MV statistics to animal studies.

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