PMID- 30218784 OWN - NLM STAT- MEDLINE DCOM- 20200123 LR - 20210317 IS - 1090-2139 (Electronic) IS - 0889-1591 (Linking) VI - 75 DP - 2019 Jan TI - Evolution of a maternal immune activation (mIA) model in rats: Early developmental effects. PG - 48-59 LID - S0889-1591(18)30557-9 [pii] LID - 10.1016/j.bbi.2018.09.005 [doi] AB - Maternal immune activation (mIA) in rodents is rapidly emerging as a key model for neurodevelopmental disorders such as autism spectrum disorder (ASD) and schizophrenia. Here, we optimise a mIA model in rats, aiming to address certain limitations of current work in this field. Specifically, the lack of clear evidence for methodology chosen, identification of successful induction of mIA in the dams and investigation of male offspring only. We focus on gestational and early juvenile changes in offspring following mIA, as detailed information on these critical early developmental time points is sparse. Following strain (Wistar, Lister Hooded, Sprague Dawley) comparison and selection, and polyriboinosinic-polyribocytidylic acid (poly I:C) dose selection (2.5-15 mg/kg single or once daily for 5 days), mIA was induced in pregnant Wistar rats with 10 mg/kg poly I:C i.p. on gestational day (GD) 15. Early morphometric analysis was conducted in male and female offspring at GD21 and postnatal day (PD) 21, eight dams for each treatment at each time point were used, 32 in total. Subsequent microglia analysis was conducted at PD21 in a small group of offspring. Poly I:C at 10 mg/kg i.p. induced a robust, but variable, plasma IL-6 response 3 h post-injection and reduced body weight at 6 h and 24 h post-injection in two separate cohorts of Wistar rats at GD15. Plasma IL-6 was not elevated at PD21 in offspring or dams. Poly I:C-induced mIA did not affect litter numbers, but resulted in PD21 pup, and GD21 placenta growth restriction. Poly I:C significantly increased microglial activation at PD21 in male hippocampi. We have identified 10 mg/kg poly I:C i.p on GD15 as a robust experimental approach for inducing mIA in Wistar rats and used this to identify early neurodevelopmental changes. This work provides a framework to study the developmental trajectory of disease-relevant, sex-specific phenotypic changes in rats. CI - Copyright (c) 2018 Elsevier Inc. All rights reserved. FAU - Murray, Katie N AU - Murray KN AD - Division of Pharmacy and Optometry, School of Health Sciences, Faculty of Medicine, Biology and Health, University of Manchester, Manchester M13 9PT, United Kingdom. FAU - Edye, Michelle E AU - Edye ME AD - Division of Pharmacy and Optometry, School of Health Sciences, Faculty of Medicine, Biology and Health, University of Manchester, Manchester M13 9PT, United Kingdom. FAU - Manca, Maurizio AU - Manca M AD - Division of Pharmacy and Optometry, School of Health Sciences, Faculty of Medicine, Biology and Health, University of Manchester, Manchester M13 9PT, United Kingdom. FAU - Vernon, Anthony C AU - Vernon AC AD - King's College London, Institute of Psychiatry, Psychology and Neuroscience, Department of Basic and Clinical Neuroscience, Maurice Wohl Clinical Neuroscience Institute, 5 Cutcombe Road, London SE5 9RT, United Kingdom; King's College London, MRC Centre for Neurodevelopmental Disorders, New Hunt's House, Guy's Hospital Campus, London SE1 1UL, United Kingdom. FAU - Oladipo, Joanna M AU - Oladipo JM AD - Division of Pharmacy and Optometry, School of Health Sciences, Faculty of Medicine, Biology and Health, University of Manchester, Manchester M13 9PT, United Kingdom. FAU - Fasolino, Victoria AU - Fasolino V AD - Division of Pharmacy and Optometry, School of Health Sciences, Faculty of Medicine, Biology and Health, University of Manchester, Manchester M13 9PT, United Kingdom. FAU - Harte, Michael K AU - Harte MK AD - Division of Pharmacy and Optometry, School of Health Sciences, Faculty of Medicine, Biology and Health, University of Manchester, Manchester M13 9PT, United Kingdom. FAU - Mason, Varsha AU - Mason V AD - Division of Pharmacy and Optometry, School of Health Sciences, Faculty of Medicine, Biology and Health, University of Manchester, Manchester M13 9PT, United Kingdom. FAU - Grayson, Ben AU - Grayson B AD - Division of Pharmacy and Optometry, School of Health Sciences, Faculty of Medicine, Biology and Health, University of Manchester, Manchester M13 9PT, United Kingdom. FAU - McHugh, Patrick C AU - McHugh PC AD - Centre for Biomarker Research and Department of Pharmacy, School of Applied Sciences, University of Huddersfield, HD1 3DH, United Kingdom. FAU - Knuesel, Irene AU - Knuesel I AD - Roche Innovation Center Basel, 124 Grenzacherstrasse, Basel, CH 4070, Switzerland. FAU - Prinssen, Eric P AU - Prinssen EP AD - Roche Innovation Center Basel, 124 Grenzacherstrasse, Basel, CH 4070, Switzerland. FAU - Hager, Reinmar AU - Hager R AD - Division of Evolution and Genomic Sciences, School of Biological Sciences, Faculty of Medicine, Biology and Health, University of Manchester, Manchester M13 9PT, United Kingdom. Electronic address: Reinmar.Hager@manchester.ac.uk. FAU - Neill, Joanna C AU - Neill JC AD - Division of Pharmacy and Optometry, School of Health Sciences, Faculty of Medicine, Biology and Health, University of Manchester, Manchester M13 9PT, United Kingdom. Electronic address: joanna.neill@manchester.ac.uk. LA - eng GR - MC_PC_13070/MRC_/Medical Research Council/United Kingdom GR - MR/N025377/1/MRC_/Medical Research Council/United Kingdom GR - MR/N026063/1/MRC_/Medical Research Council/United Kingdom PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20180912 PL - Netherlands TA - Brain Behav Immun JT - Brain, behavior, and immunity JID - 8800478 RN - 0 (Cytokines) RN - 0 (Interleukin-6) RN - O84C90HH2L (Poly I-C) SB - IM MH - Animals MH - Behavior, Animal/physiology MH - Cytokines/immunology MH - Disease Models, Animal MH - Female MH - Hippocampus/drug effects MH - Immunity, Active/immunology/*physiology MH - Interleukin-6/metabolism MH - Lymphocyte Activation/*immunology/physiology MH - Male MH - Models, Animal MH - Motor Activity/drug effects MH - Neurodevelopmental Disorders MH - Placenta/metabolism MH - Poly I-C/pharmacology MH - Pregnancy MH - Prenatal Exposure Delayed Effects/*immunology MH - Rats MH - Rats, Wistar MH - Schizophrenia/immunology MH - T-Lymphocytes/immunology OTO - NOTNLM OT - IL-6 OT - Microglia OT - Placenta OT - Poly I:C OT - Wistar rat OT - mIA (maternal immune activation) EDAT- 2018/09/16 06:00 MHDA- 2020/01/24 06:00 CRDT- 2018/09/16 06:00 PHST- 2018/06/15 00:00 [received] PHST- 2018/08/05 00:00 [revised] PHST- 2018/09/04 00:00 [accepted] PHST- 2018/09/16 06:00 [pubmed] PHST- 2020/01/24 06:00 [medline] PHST- 2018/09/16 06:00 [entrez] AID - S0889-1591(18)30557-9 [pii] AID - 10.1016/j.bbi.2018.09.005 [doi] PST - ppublish SO - Brain Behav Immun. 2019 Jan;75:48-59. doi: 10.1016/j.bbi.2018.09.005. Epub 2018 Sep 12.