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

Mueller, F; Richetto, Juliet; Hayes, Lindsay N.; Zambon, Alice; Pollak, Daniela D.; Sawa, Akira; Meyer, Urs; Weber‐Stadlbauer, Ulrike

doi:10.1016/j.bbi.2019.04.019

Cited by 110 publications

(125 citation statements)

References 59 publications

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“…Several variables previously identified as critical in the MIA model were confirmed by applying penalized regression to our MIA dataset. Firstly, maternal weight loss and hypothermia were negatively associated with the MIA class confirming that the intensity of immune activation is critical as recently reported [10,11]. Secondly, decreased litter size was associated with the MIA class, confirming that MIA could induce partial abortions and therefore reduce litter size as reported in some but not all studies [11].…”

Section: Discussionsupporting

confidence: 73%

“…Firstly, maternal weight loss and hypothermia were negatively associated with the MIA class confirming that the intensity of immune activation is critical as recently reported [10,11]. Secondly, decreased litter size was associated with the MIA class, confirming that MIA could induce partial abortions and therefore reduce litter size as reported in some but not all studies [11]. Thirdly, higher BW was associated with the MIA class, a result which is in partial agreement with a study in which the fat mass was increased in the MIA adult progeny [25], but not with others in which MIA pups exhibited a decreased BW [26,27].…”

Section: Discussionsupporting

confidence: 66%

“…To obtain a high-confidence dataset, we followed the recommended guidelines for the MIA model [10,11]. Females were mated with males for 16h (6 p.m.-10 a.m. next day, considered embryonic day (E) 0.5), by groups of 3 females for 1 male.…”

Section: Methodsmentioning

confidence: 99%

“…After mating, females were left undisturbed, with the exception of weekly cage cleaning. Pregnant dams (identified based on minimal body weight (BW) gain of 3 g between E0.5-E11.5) were randomly assigned to the experimental groups and injected with poly(I:C) (n=13) or vehicle (saline, n=8) at E12.5 between 9-10 p.m. Due to previously reported intra-lot variability of poly(I:C) [11,13], a single lot (reference P9582, Sigma-Aldrich) was dissolved in sterile double-distilled water at room 6 temperature (RT) to generate a stock solution based on pure poly(I:C) weight (20µg/µL). Stock solution was aliquoted and stored at -20°C until use.…”

Section: Methodsmentioning

confidence: 99%

“…Hence, in animal studies in which complex phenotypes are analyzed and/or inter-individual variability is difficult to control, standard parametric or non-parametric analysis between groups (Student's t-test, Mann-Whitney test, ANOVA, Kruskal-Wallis) or pairwise correlations between variables (Pearson's correlation, Spearman's correlation) only provide limited insight into the complexity of the interactions between variables. This is particularly the case in the MIA model in which the progeny phenotype can be heavily influenced in unpredictable ways by experimental conditions [10,11]. We therefore believe that animal studies in general, and notably the MIA model, could benefit from MV analyzes to model the effects of variables on the outcome of interest.…”

Section: Introductionmentioning

confidence: 99%

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

Paraschivescu

Barbosa

Lorivel

et al. 2020

Preprint

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Maternal 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. Keywords (6):neurodevelopmental disorder autism spectrum disorder behavior maternal immune activation animal model multivariable analysis

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Section: Discussionsupporting

confidence: 73%

Section: Discussionsupporting

confidence: 66%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

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

Paraschivescu

Barbosa

Lorivel

et al. 2020

Preprint

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Age‐related changes in behavior profile in male offspring of rats treated with poly I:C‐induced maternal immune activation in early gestation

Chen,

Meng,

Fang

et al. 2024

Anim Models and Exp Med

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BackgroundAutism and schizophrenia are environmental risk factors associated with prenatal viral infection during pregnancy. It is still unclear whether behavior phenotypes change at different developmental stages in offspring following the activation of the maternal immune system.MethodsSprague–Dawley rats received a single caudal vein injection of 10 mg/kg polyinosinic:polycytidylic acid (poly I:C) on gestational day 9 and the offspring were comprehensively tested for behaviors in adolescence and adulthood.ResultsMaternal serum levels of interleukin (IL)‐6, IL‐1β and tumor necrosis factor‐α were elevated in poly I:C‐treated dams. The offspring of maternal poly I:C‐induced rats showed increased anxiety, impaired social approach, and progressive impaired cognitive and sensorimotor gating function.ConclusionMaternal immune activation led to developmental specificity behavioral impairment in offspring.

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Maternal immune activation accelerates puberty initiation and alters mechanical allodynia in male and female C57BL6/J mice

Zhao

Erickson

Mohammed

et al. 2022

Developmental Psychobiology

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The mechanisms that link maternal immune activation (MIA) with the onset of neurodevelopmental disorders remain largely unclear. Accelerated puberty is also associated with a heightened risk for psychopathology in later life, but there is a dearth of evidence on the impacts of maternal infection on pubertal timing. We examined the effects of MIA on reproductive development, mechanical allodynia, and sensorimotor gating in juvenile, adolescent, and adult male and female mice. Moreover, we investigated hypothalamic neural markers associated with the reproductive and stress axes. Finally, we tested the mitigating effects of environmental enrichment (EE), which has clinical relevancy in human rehabilitation settings. Our results show that administration of polyinosinic–polycytidylic acid (poly(I:C)) on gestational day 12.5 led to early preputial separation, vaginal openings, and age of first estrus in offspring. MIA exposure altered pain sensitivity across development and modestly altered prepulse inhibition. The downregulation of Nr3c1 and Oprk mRNA in the hypothalamus of juvenile mice suggests that MIA's effects may be mediated through disruption of hypothalamic–pituitary–adrenal axis activity. In contrast, life‐long housing with EE rescued many of these MIA‐induced consequences. Overall, our findings suggest that accelerated puberty may be associated with the deleterious effects of infection during pregnancy and the onset of psychopathology.

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

Cited by 110 publications

References 59 publications

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

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

Age‐related changes in behavior profile in male offspring of rats treated with poly I:C‐induced maternal immune activation in early gestation

Maternal immune activation accelerates puberty initiation and alters mechanical allodynia in male and female C57BL6/J mice

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