Maternal Immune Activation by Lipopolysaccharide Reduced Parvalbumin Levels and Increased Perineuronal Nets in the Prefrontal Cortex Without Inducing Schizophrenia-like Behavioral Deficits in PV-Cre Long-Evans Rats

Models of maternal immune activation (MIA) often lead to parvalbumin-positive (PV+) interneuron deficits and behavioral alterations resembling autism or schizophrenia. We aimed to characterize the effects of MIA in PV-Cre Long-Evans rats. Pregnant dams received 8 lipopolysaccharide injections (1 mg/kg), on alternating days, starting with gestational day 7. The offspring behavior was tested from postnatal day 5 to adulthood, with tasks assessing motor development, anxiety, exploration, social behavior and sensorimotor gating. Morphological changes in the brain, density of PV+ interneurons and perineuronal nets in the prefrontal cortex, as well as the quantity of PV protein were measured at selected timepoints. We found that MIA in PV-Cre Long-Evans rats failed to elicit the expected schizophrenia- or autism-like deficits. Decrease in PV protein in the prefrontal cortex was present without corresponding decrement of PV+ interneurons, with a paradoxical increase in perineuronal net counts. PV-Cre Long-Evans rat line reacts to the MIA protocol very differently than Wistar rats in previously published studies and is suboptimal for studies of schizophrenia- or autism-like behavioral deficits. Genetic background seems to be an important factor for the outcome in MIA rodent models.