Exposure to in utero inflammation increases locomotor activity, alters cognitive performance and drives vulnerability to cognitive performance deficits after acute immune activation

Brain, Behavior, and Immunity
Ryan MakinsonT M Reyes

Abstract

Fetal exposure to intrauterine inflammation (IUI) affects brain development. Using intrauterine lipopolysaccharide (LPS) administration to induce a localized, rather than a systemic, inflammation, we have previously shown that IUI increases cytokine expression and microglia number, and reduces white matter in the brains of exposed offspring. Clinical data suggest that IUI may increase the risk for cognitive and neurodevelopmental disorders, however, IUI is often found in the context of preterm birth, making it difficult to disentangle the adverse effects of inflammation from those related to prematurity. Therefore, using a mouse model of IUI that does not involve preterm birth, operant tasks were used to evaluate motivation, attention, impulsivity, and locomotion. IUI-exposed offspring were found to have increased locomotion and increased motivation (females only), and testing in the 5-choice serial reaction time task (5-CSRTT) showed that IUI-exposed offspring performed more trials and could respond accurately at a shorter stimulus length. We have previously shown that IUI animals have a potentiated cytokine response to a "second hit" (acute LPS injection) in adulthood, so animals' performance in the 5CSRTT was evaluated follo...Continue Reading

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