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

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.

SUBMITTER: Vojtechova I

PROVIDER: S-EPMC8004756 | biostudies-literature | 2021 Mar

REPOSITORIES: biostudies-literature

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

Vojtechova Iveta I Maleninska Kristyna K Kutna Viera V Klovrza Ondrej O Tuckova Klara K Petrasek Tomas T Stuchlik Ales A

International journal of molecular sciences 20210323 6

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 examin ...[more]

PMID: 33806936

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Project description:IntroductionAccess to electric light has exposed living organisms to varying intensities of light throughout the 24 h day. Dim light at night (DLAN) is an inappropriate signal for the biological clock, which is responsible for the circadian organization of physiology. During the gestational period, physiological adaptations occur to ensure a successful pregnancy and optimal fetal development. Environmental maternal conditions, such as disruptions of maternal circadian rhythms, could negatively affect offspring health. We have previously demonstrated that exposure of female Wistar rats to DLAN results in circadian, metabolic, and behavioral alterations. A relevant behavior during adolescence is social play, primarily regulated by the nucleus accumbens (NAc) which is crucial for the proper performance of important behaviors in adulthood. Throughout development, microglia are responsible for the remodeling of diverse brain regions via synaptic pruning. During adolescence, this process occurs within the NAc, where immune-mediated remodeling directly impacts social play behavior.MethodsThis study investigated the effects of maternal exposure to DLAN or a light-dark cycle (LD) before (5 weeks) and during the gestational period (21-23 days) on the metabolism and behavior of offspring in adolescence and adulthood. Body mass was measured every 5 days from postnatal day 1 (PN1) to PN25 and every 10 days from PN40 to PN90; food consumption was monitored weekly from PN40 to PN90. Social play behavior was evaluated at PN40. The quantification and morphology of microglia in the NAc were measured on PN30. An open field test was conducted at PN60, and anhedonia test was assessed at PN90.Results and discussionMale and female offspring from mothers exposed to DLAN showed increased body mass gain at PN25. DLAN male offspring had lower food consumption, while DLAN females exhibited increased food consumption. In social play behavior, no differences were found between DLAN and LD female offspring. In contrast, DLAN male offspring exhibited a significant decrease in social play behavior compared to LD animals, which was associated with higher numbers of microglia in the NAc that had more ramified morphology. Importantly, at PN90, DLAN offspring presented increased anxiety-like behaviors. These results demonstrate that DLAN exposure induces intergenerational behavioral alterations that persist until adulthood.

Dataset Information

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

Publications

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

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