Evolution of a maternal immune activation (mIA) model in rats: early developmental effects

Katie N. Murray, Michelle E. Edye, Maurizio Manca, Anthony C. Vernon, Joanna M. Oladipo, Victoria Fasolino, Michael K. Harte, Varsha Mason, Ben Grayson, Patrick C. McHugh, Irene Knuesel, Eric P. Prinssen, Reinmar Hager, Joanna C. Neill

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57 Citations (Scopus)
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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 area. 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, Hooded Lister, 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, IL-6 response and reduced body weight at 6 h and 24 h post-injection in two separate cohorts of Wistar rats at GD15. IL-6 was not elevated at PD23 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.
Original languageEnglish
Pages (from-to)48-59
JournalBrain, Behavior, and Immunity
Issue number0
Early online date12 Sept 2018
Publication statusPublished - 1 Jan 2019


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