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Modeling Encephalopathy of Prematurity Using Prenatal Hypoxia-ischemia with Intra-amniotic Lipopolysaccharide in Rats
Published on: November 20, 2015
Prenatal lipopolysaccharide reduces social behavior in male offspring
Thiago B Kirsten1, Marina Taricano, Paulo C Maiorka
1Neuroimmunomodulation Research Group, Department of Pathology, School of Veterinary Medicine, University of São Paulo, São Paulo, Brazil.
Insights
Maternal sickness behavior during pregnancy, induced by lipopolysaccharide (LPS), impaired male offspring
Area of Science:
- Neuroscience
- Developmental Biology
- Behavioral Science
Background:
- Maternal immune activation during pregnancy is linked to neurodevelopmental and behavioral outcomes in offspring.
- Sickness behavior in the dam, a response to infection or inflammation, may serve as an indicator of prenatal stress exposure.
Purpose of the Study:
- To investigate the impact of maternal sickness behavior induced by lipopolysaccharide (LPS) on the developmental and behavioral trajectory of male offspring.
- To determine if prenatal exposure to LPS affects social interaction, play behavior, and anxiety-like behaviors in male rats.
Main Methods:
- Pregnant Wistar rats received an intraperitoneal injection of lipopolysaccharide (LPS) on gestation day 9.5.
- Offspring were evaluated for physical development, play behavior, social interaction, anxiety-like behavior (plus maze), and brain morphology.
- Maternal sickness behavior, including activity and weight changes, was monitored.
Main Results:
- LPS administration reduced maternal activity, food intake, and weight gain without inducing fever.
- Offspring exhibited reduced play behavior and decreased adult social interaction.
- No significant differences were observed in litter size, physical development, anxiety-like behavior, or brain morphology between groups.
Conclusions:
- Prenatal exposure to LPS, mimicking maternal sickness behavior, negatively impacts male offspring's social behavior from infancy through adulthood.
- These behavioral deficits may stem from altered motivational states or increased anxiety in the offspring.
- The findings highlight the critical role of the prenatal environment in shaping offspring social behavior and emotional regulation.
Objective:
This study investigated the relationship between maternal sickness behavior during pregnancy and offspring development and behavior.
Methods:
Pregnant Wistar rats were administered with lipopolysaccharide (LPS, 100 microg/kg, i.p.) on gestation day (GD) 9.5. Dams' sickness behavior was analyzed, and at birth, offspring number and weight were evaluated. Male offspring was evaluated through physical development, play behavior, adult social interaction, plus maze studies and morphological analysis of the brain.
Results:
Results, with respect to the control group, showed that: (1) LPS decreased general activity, food intake, and weight gain in dams, but no pyrexia was observed following treatment; (2) LPS reduced litter size, but no alterations in physical development were observed; (3) LPS reduced play behavior parameters in baby rats; (4) LPS decreased adult social interaction; (5) no alterations were observed between groups on plus maze studies; (6) no differences were observed between groups on morphological analyses of the brain.
Conclusion:
These data reveal that LPS administered on GD 9.5 impaired male offspring's social behavior in infancy and adulthood. These results may be related to an alteration in motivational states or/and increased anxiety.

