Influence of poly(I:C) variability on thermoregulation, immune responses and pregnancy outcomes in mouse models of maternal immune activation
| Autor: | Juliet Richetto, Flavia Mueller, Urs Meyer, Ulrike Weber-Stadlbauer, Daniela D. Pollak, Alice Zambon, Lindsay N. Hayes, Akira Sawa |
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| Přispěvatelé: | University of Zurich, Meyer, Urs |
| Jazyk: | angličtina |
| Rok vydání: | 2019 |
| Předmět: |
Lipopolysaccharides
0301 basic medicine Lipopolysaccharide Placenta Autism chemistry.chemical_compound Behavioral Neuroscience 0302 clinical medicine Pregnancy 2802 Behavioral Neuroscience Maternal immune activation (MIA) Pregnancy Complications Infectious Chemistry Immunogenicity Pregnancy Outcome Thermoregulation Phenotype 3. Good health 2807 Endocrine and Autonomic Systems medicine.anatomical_structure Cytokines Female medicine.symptom Infection Body Temperature Regulation medicine.medical_specialty Poly(I:C) Immunology Inflammation Double Maternal Physiology 03 medical and health sciences Fetus Immune system Internal medicine medicine Animals Animal model 2403 Immunology Endocrine and Autonomic Systems 10079 Institute of Veterinary Pharmacology and Toxicology stranded RNA Mice Inbred C57BL Disease Models Animal Poly I-C 030104 developmental biology Endocrinology Schizophrenia RNA 570 Life sciences biology 030217 neurology & neurosurgery |
| Popis: | Maternal immune activation (MIA) models that are based on administration of the viral mimetic, poly(I:C), are widely used as experimental tools to study neuronal and behavioral dysfunctions in relation to immune-mediated neurodevelopmental disorders and mental illnesses. Evidence from investigations in non-pregnant rodents suggests that different poly(I:C) products can vary in terms of their immunogenicity, even if they are obtained from the same vendor. The present study aimed at extending these findings to pregnant mice, while also controlling various poly(I:C) products for potential contamination with lipopolysaccharide (LPS). We found significant variability between different batches of poly(I:C) potassium salt obtained from the same vendor (Sigma-Aldrich) in terms of the relative amount of dsRNA fragments in the high molecular weight range (1000-6000 nucleotides long) and with regards to their effects on maternal thermoregulation and immune responses in maternal plasma, placenta and fetal brain. Batches of poly(I:C) potassium salt containing larger amounts of high molecular weight fragments induced more extensive effects on thermoregulation and immune responses compared to batches with minimal amounts of high molecular weight fragments. Consistent with these findings, poly(I:C) enriched for high molecular weight dsRNA (HMW) caused larger maternal and placental immune responses compared to low molecular weight (LMW) poly(I:C). These variable effects were unrelated to possible LPS contamination. Finally, we found marked variability between different batches of the poly(I:C) potassium salt in terms of their effects on spontaneous abortion rates. This batch-to-batch variability was confirmed by three independent research groups using distinct poly(I:C) administration protocols in mice. Taken together, the present data confirm that different poly(I:C) products can induce varying immune responses and can differentially affect maternal physiology and pregnancy outcomes. It is therefore pivotal that researchers working with poly(I:C)-based MIA models ascertain and consider the precise molecular composition and immunogenicity of the product in use. We recommend the establishment of reference databases that combine phenotype data with empirically acquired quality information, which can aid the design, implementation and interpretation of poly(I:C)-based MIA models. |
| Databáze: | OpenAIRE |
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