title: Maternal viral infection during pregnancy elicits anti-social behavior in neonatal piglet offspring independent of postnatal microglial cell activation.
abstract: Maternal infection during pregnancy increases risk for neurodevelopmental disorders and reduced stress resilience in offspring, but the mechanisms are not fully understood. We hypothesized that piglets born from gilts infected with a respiratory virus during late gestation would exhibit aberrant microglia activity, cognitive deficits and reduced sociability. Pregnant gilts were inoculated with porcine reproductive and respiratory syndrome virus (PRRSV; 5×105TCID50of live PRRSV) or saline at gestational day 76. Gilts infected with PRRSV exhibited fever (p<0.01) and reduced appetite (p<0.001) for 2weekspost-inoculation and were PRRSV-positive at parturition. Piglets born from infected and control gilts were weaned at postnatal day (PD) 1 and assigned to two groups. Group 1 was challenged with lipopolysaccharide (LPS, 5μg/kg body weight i.p.) or saline on PD 14 and tissues were collected. Group 2 was tested in a T-maze task to assess spatial learning and in a 3-chamber arena with unfamiliar conspecifics to assess social behavior from PD 14-27. Microglia (CD11b+CD45low) isolated from Group 2 piglets at PD 28 were challenged ex vivo with LPS; a subset of cells was analyzed for MHCII expression. Maternal infection did not affect offspring circulating TNFα, IL-10, or cortisol levels basally or 4h post-LPS challenge. While performance in the T-maze task was not affected by maternal infection, both sociability and preference for social novelty were decreased in piglets from infected gilts. There was no effect of maternal infection on microglial MHCII expression or LPS-induced cytokine production. Taken together, these results suggest the reduced social behavior elicited by maternal infection is not due to aberrant microglia activity postnatally.
authors.affiliation: Department of Animal Sciences, University of Illinois Urbana-Champaign, Urbana, IL, USA; Integrative Immunology and Behavior Program, University of Illinois Urbana-Champaign, Urbana, IL, USA.
authors.forename: Adrienne M
authors.initials: AM
authors.lastname: Antonson
authors.affiliation: Department of Animal Sciences, University of Illinois Urbana-Champaign, Urbana, IL, USA; Integrative Immunology and Behavior Program, University of Illinois Urbana-Champaign, Urbana, IL, USA.
authors.forename: Emily C
authors.initials: EC
authors.lastname: Radlowski
authors.affiliation: Department of Animal Sciences, University of Illinois Urbana-Champaign, Urbana, IL, USA; Integrative Immunology and Behavior Program, University of Illinois Urbana-Champaign, Urbana, IL, USA; Neuroscience Program, University of Illinois Urbana-Champaign, Urbana, IL, USA.
authors.forename: Marcus A
authors.initials: MA
authors.lastname: Lawson
authors.affiliation: Department of Animal Sciences, University of Illinois Urbana-Champaign, Urbana, IL, USA; Integrative Immunology and Behavior Program, University of Illinois Urbana-Champaign, Urbana, IL, USA.
authors.forename: Jennifer L
authors.initials: JL
authors.lastname: Rytych
authors.affiliation: Department of Animal Sciences, University of Illinois Urbana-Champaign, Urbana, IL, USA; Integrative Immunology and Behavior Program, University of Illinois Urbana-Champaign, Urbana, IL, USA; Neuroscience Program, University of Illinois Urbana-Champaign, Urbana, IL, USA; Division of Nutritional Sciences, University of Illinois Urbana-Champaign, Urbana, IL, USA. Electronic address: rwjohn@illinois.edu.
authors.forename: Rodney W
authors.initials: RW
authors.lastname: Johnson
mesh_terms: D000818:Animals; D000987:Antisocial Personality Disorder / Q000523:psychology*; D016207:Cytokines / Q000097:blood; D005260:Female; D005802:Genes, MHC Class II / Q000235:genetics; D008070:Lipopolysaccharides / Q000494:pharmacology; D008262:Macrophage Activation; D008568:Memory; D017628:Microglia / Q000276:immunology*; D019318:Porcine Reproductive and Respiratory Syndrome / Q000276:immunology* / Q000523:psychology* / Q000821:virology; D019316:Porcine respiratory and reproductive syndrome virus; D011247:Pregnancy; D011251:Pregnancy Complications, Infectious; D011297:Prenatal Exposure Delayed Effects / Q000523:psychology; D012919:Social Behavior; D065853:Spatial Learning / Q000187:drug effects; D034421:Sus scrofa; D013552:Swine
chemical_list: D016207:Cytokines; D008070:Lipopolysaccharides
keywords: Cytokines; Maternal immune activation; Microglia; Piglet; Prenatal; Social behavior