Prenatal Infection Affects the Neuronal Architecture and Cognitive Function in Adult Mice

Environmental factors such as prenatal infection are involved in the pathogenic processes of neurodevelopnnental psychiatric disorders. In the present study, we administered a viral mimic, polyriboinosinic-polyribocytidylic acid (poly I:C, 20 mg/kg, i.p.), to pregnant B6 mice at gestational day 9.5. Neonates born to these poly I:C-treated dams showed an increase of microglia in the hippocampus, indicating an activation of the immune system in the brains. Moreover, a significant increase in the number of dopamine-producing neurons in the ventral tegmental area was observed in adult male poly I:C offspring compared with age-matched saline offspring. Poly I:C offspring also exhibited hypolocomotor activity in a novel open-field arena but did not display signs of anxiety or depression in the elevated plus maze or the forced swim test, respectively. However, the short-term memory of the poly I:C offspring was impaired in a novel object recognition task. Therefore, the dendritic architecture of granule cells in the dentate gyrus (DG) and pyramidal neurons in the medial prefrontal cortex (mPFC) were examined. The dendritic complexity was reduced in the DG granule cells of the poly I:C offspring and exhibited shorter dendritic length compared with the saline offspring. The density of dendritic spines in the DG granule cells was also decreased in the poly I:C offspring. Furthermore, the dendritic complexity and spine density were reduced in layer II/III mPFC pyramidal neurons of the poly I:C offspring. Together, these data demonstrate impaired short-term memory and altered dendritic architecture in adult poly I:C offspring, which validates the prenatal infection paradigm as a model for neurodevelopmental psychiatric disorders. (C) 2014 S. Karger AG, Basel