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

Abstract

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.

The authors' abstract, as published at the source. International Journal of Molecular Sciences, 2026 · DOI ↗