PMID- 31415868
OWN - NLM
STAT- MEDLINE
DCOM- 20200825
LR  - 20200825
IS  - 1090-2139 (Electronic)
IS  - 0889-1591 (Linking)
VI  - 82
DP  - 2019 Nov
TI  - Poly(I:C) source, molecular weight and endotoxin contamination affect dam and 
      prenatal outcomes, implications for models of maternal immune activation.
PG  - 160-166
LID - S0889-1591(19)30745-7 [pii]
LID - 10.1016/j.bbi.2019.08.006 [doi]
AB  - The viral mimetic polyinosinic:polycytidylic acid (poly(I:C)) is increasingly 
      used to induce maternal immune activation (mIA) to model neurodevelopmental 
      disorders (NDDs). Robust and reproducible phenotypes across studies are essential 
      for the generation of models that will enhance our understanding of NDDs and 
      enable the development of improved therapeutic strategies. However, differences 
      in mIA-induced phenotypes using poly(I:C) have been widely observed, and this has 
      prompted the reporting of useful and much needed methodological guidelines. Here, 
      we perform a detailed investigation of molecular weight and endotoxin variations 
      in poly(I:C) procured from two of the most commonly used suppliers, Sigma and 
      InvivoGen. We demonstrate that endotoxin contamination and molecular weight 
      differences in poly(I:C) composition lead to considerable variability in maternal 
      IL-6 response in rats treated on gestational day (GD)15 and impact on fetal 
      outcomes. Specifically, both endotoxin contamination and molecular weight 
      predicted reductions in litter size on GD21. Further, molecular weight predicted 
      a reduction in placental weight at GD21. While fetal body weight at GD21 was not 
      affected by poly(I:C) treatment, male fetal brain weight was significantly 
      reduced by poly(I:C), dependent on supplier. Our data are in agreement with 
      recent reports of the importance of poly(I:C) molecular weight, and extend this 
      work to demonstrate a key role of endotoxin on relevant phenotypic outcomes. We 
      recommend that the source and batch numbers of poly(I:C) used should always be 
      stated and that molecular weight variability and endotoxin contamination should 
      be minimised for more robust mIA modelling.
CI  - Copyright (c) 2019 Elsevier Inc. All rights reserved.
FAU - Kowash, H M
AU  - Kowash HM
AD  - Division of Developmental Biology and Medicine, School of Medical Sciences, 
      Faculty of Biology, Medicine and Health, Manchester Academic Health Science 
      Centre, University of Manchester, Manchester M13 9WL, UK.
FAU - Potter, H G
AU  - Potter HG
AD  - Division of Evolution and Genomic Sciences, School of Biological Sciences, 
      Faculty of Biology, Medicine and Health, Manchester Academic Health Science 
      Centre, University of Manchester, Manchester M13 9PT, UK.
FAU - Edye, M E
AU  - Edye ME
AD  - Division of Pharmacy and Optometry, School of Health Sciences, Faculty of 
      Medicine, Biology and Health, Manchester Academic Health Science Centre, 
      University of Manchester, Manchester M13 9PT, UK.
FAU - Prinssen, E P
AU  - Prinssen EP
AD  - Roche Innovation Centre, Basel, 124 Grenzacherstrasse, Basel, CH 4070, 
      Switzerland.
FAU - Bandinelli, S
AU  - Bandinelli S
AD  - Roche Innovation Centre, Basel, 124 Grenzacherstrasse, Basel, CH 4070, 
      Switzerland.
FAU - Neill, J C
AU  - Neill JC
AD  - Division of Pharmacy and Optometry, School of Health Sciences, Faculty of 
      Medicine, Biology and Health, Manchester Academic Health Science Centre, 
      University of Manchester, Manchester M13 9PT, UK. Electronic address: 
      http://www.b-neuro.com.
FAU - Hager, R
AU  - Hager R
AD  - Division of Evolution and Genomic Sciences, School of Biological Sciences, 
      Faculty of Biology, Medicine and Health, Manchester Academic Health Science 
      Centre, University of Manchester, Manchester M13 9PT, UK.
FAU - Glazier, J D
AU  - Glazier JD
AD  - Division of Developmental Biology and Medicine, School of Medical Sciences, 
      Faculty of Biology, Medicine and Health, Manchester Academic Health Science 
      Centre, University of Manchester, Manchester M13 9WL, UK; Division of Evolution 
      and Genomic Sciences, School of Biological Sciences, Faculty of Biology, Medicine 
      and Health, Manchester Academic Health Science Centre, University of Manchester, 
      Manchester M13 9PT, UK.
LA  - eng
PT  - Journal Article
DEP - 20190812
PL  - Netherlands
TA  - Brain Behav Immun
JT  - Brain, behavior, and immunity
JID - 8800478
RN  - 0 (Cytokines)
RN  - 0 (Endotoxins)
RN  - O84C90HH2L (Poly I-C)
SB  - IM
MH  - Animals
MH  - Behavior, Animal/physiology
MH  - Cytokines/immunology
MH  - Endotoxins
MH  - Female
MH  - Fetus/*immunology
MH  - Infectious Disease Transmission, Vertical
MH  - Litter Size
MH  - Male
MH  - Maternal Exposure
MH  - Neurodevelopmental Disorders/etiology/immunology
MH  - Poly I-C/*chemistry/pharmacology
MH  - Pregnancy
MH  - Prenatal Exposure Delayed Effects/*immunology
MH  - Rats
MH  - Rats, Wistar
MH  - Reproducibility of Results
OTO - NOTNLM
OT  - Endotoxin
OT  - Fetal brain
OT  - Fetus
OT  - IL-6
OT  - Litter size
OT  - Maternal immune activation
OT  - Molecular weight
OT  - Placenta
OT  - Poly(I:C)
OT  - Sex differences
EDAT- 2019/08/16 06:00
MHDA- 2020/08/26 06:00
CRDT- 2019/08/16 06:00
PHST- 2019/07/10 00:00 [received]
PHST- 2019/08/10 00:00 [revised]
PHST- 2019/08/10 00:00 [accepted]
PHST- 2019/08/16 06:00 [pubmed]
PHST- 2020/08/26 06:00 [medline]
PHST- 2019/08/16 06:00 [entrez]
AID - S0889-1591(19)30745-7 [pii]
AID - 10.1016/j.bbi.2019.08.006 [doi]
PST - ppublish
SO  - Brain Behav Immun. 2019 Nov;82:160-166. doi: 10.1016/j.bbi.2019.08.006. Epub 2019 
      Aug 12.