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Modeling Encephalopathy of Prematurity Using Prenatal Hypoxia-ischemia with Intra-amniotic Lipopolysaccharide in Rats
Published on: November 20, 2015
Neonatal behavioral changes in rats with gestational exposure to lipopolysaccharide: a prenatal infection model for
Moogeh Baharnoori1, Sanjeev K Bhardwaj, Lalit K Srivastava
1Douglas Mental Health University Institute, Department of Psychiatry, McGill University, 6875 LaSalle Boulevard, Montreal, Quebec, Canada.
Insights
Prenatal exposure to lipopolysaccharide (LPS) in rats impairs early social communication and learning in offspring. These findings suggest prenatal immune activation may contribute to developmental neuropsychiatric disorders.
Area of Science:
- Neuroscience
- Developmental Psychology
- Immunology
Background:
- Prenatal infections are linked to developmental neuropsychiatric disorders like schizophrenia and autism.
- Early behavioral changes in rodent models of prenatal infection are not well understood.
Purpose of the Study:
- To investigate the effects of prenatal immune activation on early neurodevelopmental and behavioral outcomes.
- To characterize early neurophenotypic presentations in a prenatal lipopolysaccharide (LPS) rat model.
Main Methods:
- Pregnant Sprague-Dawley rats received LPS (100 μg/kg) on gestational days 15 and 16.
- Offspring were assessed for maternal behavior, physical development, ultrasonic vocalizations, nest-seeking, and associative learning.
- Cortical gene expression of 5HT1A and 5HT1B was analyzed.
Main Results:
- Prenatal LPS exposure did not affect maternal behavior or physical development.
- A significant decrease in ultrasonic vocalization number and duration was observed at postnatal days 3 and 5.
- Impairments in nest-seeking behavior and odor-stroke associative learning were noted at postnatal days 8 and 9.
- Reduced cortical 5HT1A and 5HT1B messenger RNA expression was detected at postnatal day 3.
Conclusions:
- Prenatal immune activation via LPS significantly impairs neonatal social/communicative behavior and learning.
- These early behavioral deficits may be relevant to childhood and premorbid abnormalities in autism and schizophrenia.
- Early molecular changes in serotonin receptors may underlie observed behavioral alterations.
Abstract:
Exposure to prenatal infections has been widely associated with the increased risk for neuropsychiatric disorders of developmental origin such as schizophrenia and autism. Although several behavioral and cognitive deficits have been detected during adulthood in rodent models of prenatal infections, early behavioral changes have not been well characterized. In a prenatal lipopolysaccharide (LPS) model, we have previously observed significant alterations in the neuronal cytoarchitecture during early postnatal life. In the present study, we aimed to investigate the potential effects of prenatal immune activation on early neurophenotypic presentations using a set of behavioral test battery. Female Sprague-Dawley rats were administered with 100 μg/kg LPS (intraperitoneally) at gestational days 15 and 16. During the first postnatal week, we found no significant effect on maternal behavior or mother-pup interaction by this treatment. Also, no major changes in physical developmental milestones of pups were noted from postnatal (P) days P6 to P16. Importantly, prenatal LPS-exposed pups had a significant decrease in the number and duration of ultrasonic vocalization calls at P3 and P5. Prenatal LPS treatment also led to impairments in nest-seeking behavior and odor-stroke associative learning in neonatal rats at P8 and P9. At the molecular level, we detected significant decrease in the expression of cortical 5HT1A and 5HT1B messenger RNA at P3. These data suggest that prenatal exposure to an immune activator can significantly impair the social/communicative behavior in the neonate offspring, which may be relevant to childhood and premorbid abnormalities reported in autism and schizophrenia subjects.
