TY - JOUR T1 - Prospective Analysis of the Effects of Maternal Immune Activation on Rat Cytokines during Pregnancy and Behavior of the Male Offspring Relevant to Schizophrenia JF - eneuro JO - eNeuro DO - 10.1523/ENEURO.0249-18.2018 SP - ENEURO.0249-18.2018 AU - Brittney R. Lins AU - Jessica L. Hurtubise AU - Andrew J. Roebuck AU - Wendie N. Marks AU - Nadine K. Zabder AU - Gavin A. Scott AU - Quentin Greba AU - Wojciech Dawicki AU - Xiaobei Zhang AU - Christopher D. Rudulier AU - John R. Gordon AU - John G. Howland Y1 - 2018/08/14 UR - http://www.eneuro.org/content/early/2018/08/14/ENEURO.0249-18.2018.abstract N2 - Influenza during pregnancy is associated with the development of psychopathology in the offspring. We sought to determine if maternal cytokines produced following administration of viral mimetic polyI:C to pregnant rats were predictive of behavioral abnormalities in the adult offspring. Timed-pregnant Sprague-Dawley rats received a single intravenous injection of 4 mg/kg polyI:C or saline on gestational day 15. Blood was collected for serum analysis of cytokine levels with ELISA. Male offspring were tested in a battery of behavioral tests at adulthood and behavior correlated with maternal cytokine levels. Maternal serum levels of CXCL1 and IL-6, but not TNF-α or CXCL2, were elevated in polyI:C-treated dams. PolyI:C-treated dams experienced post-treatment weight loss and polyI:C pups were smaller than controls at postnatal day 1. Various behavior alterations were seen in the polyI:C-treated offspring. Male polyI:C offspring had enhanced MK-801-induced locomotion, and reduced sociability. PolyI:C offspring failed to display crossmodal and visual memory, and oddity preference was also impaired. Set-shifting, assessed with a lever-based operant conditioning task, was facilitated while touchscreen-based reversal learning was impaired. Correlations were found between maternal serum concentrations of CXCL1, acute maternal temperature and body weight changes, neonatal pup mass, and odd object discrimination and social behavior. Overall, while the offspring of polyI:C-treated rats displayed behavior abnormalities, maternal serum cytokines were not related to the long-term behavior changes in the offspring. Maternal sickness effects and neonatal pup size may be better indicators of later effects in the offspring.Significance Statement Psychiatric pathology is complex, poorly understood, and often results in chronic illness. Many psychiatric conditions are believed to occur as a result of genetic and environmental factors. Gestational adversity such as inflammation in pregnancy may act as a priming experience for the later emergence of psychopathologies, and accurate identification of risk factors may advise early interventions. We sought to characterize long-term behavior effects in the offspring of rats exposed to an inflammatory event during pregnancy and relate these effects to the serum levels of relevant cytokines CXCL1, IL-6, and TNF-α. Our results suggest that these maternal cytokines are not strongly related to offspring behavior outcomes, and other measures may have greater value as predictors of behavior outcomes. ER -