Maternal Immune Activation Alters Behavior of Adult Offspring: Sex-Dependent Impairment and Attenuation by Glycan

Abstract

The developing fetus is exceptionally sensitive to insult. Perturbation during this critical period of development can have lasting effects throughout offspring lifespan. Viral infection and obesity are insults that induce a proinflammatory response in the maternal host and are pertinent to adverse offspring outcomes. Attenuating the maternal inflammatory response, at the time of insult, has shown limited success on fetal outcomes; these factors are necessary for normal fetal development. Attenuating the maternal inflammatory response by increasing anti-inflammatory activity could restore or approximate homeostasis and avoid or attenuate adverse outcomes in offspring. This was tested by inducing maternal immune activation with a high-fat diet or polyinosinic:polycitidylic acid, with some dams receiving concurrent immunomodulatory glycan exposure. Adult offspring were assessed on discrimination reversal tasks and delayed matching to position, measures of behavioral flexibility and working memory, respectively. When differences in behavioral flexibility or working memory did occur, they were often in the opposite direction that was expected. In some instances glycan did attenuate changes to make these animals more similar to controls.