Behavioral Alterations and Decreased Number of Parvalbumin-Positive Interneurons in Wistar Rats after Maternal Immune Activation by Lipopolysaccharide: Sex Matters

脂多糖激活母体免疫后 Wistar 大鼠的行为改变和 Parvalbumin 阳性中间神经元数量减少:性别问题

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作者:Iveta Vojtechova, Kristyna Maleninska, Viera Kutna, Ondrej Klovrza, Klara Tuckova, Tomas Petrasek, Ales Stuchlik

Abstract

Maternal immune activation (MIA) during pregnancy represents an important environmental factor in the etiology of schizophrenia and autism spectrum disorders (ASD). Our goal was to investigate the impacts of MIA on the brain and behavior of adolescent and adult offspring, as a rat model of these neurodevelopmental disorders. We injected bacterial lipopolysaccharide (LPS, 1 mg/kg) to pregnant Wistar dams from gestational day 7, every other day, up to delivery. Behavior of the offspring was examined in a comprehensive battery of tasks at postnatal days P45 and P90. Several brain parameters were analyzed at P28. The results showed that prenatal immune activation caused social and communication impairments in the adult offspring of both sexes; males were affected already in adolescence. MIA also caused prepulse inhibition deficit in females and increased the startle reaction in males. Anxiety and hypolocomotion were apparent in LPS-affected males and females. In the 28-day-old LPS offspring, we found enlargement of the brain and decreased numbers of parvalbumin-positive interneurons in the frontal cortex in both sexes. To conclude, our data indicate that sex of the offspring plays a crucial role in the development of the MIA-induced behavioral alterations, whereas changes in the brain apparent in young animals are sex-independent.

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