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Induction of Maternal Immune Activation in Mice at Mid-gestation Stage with Viral Mimic PolyI:C
Published on: March 25, 2016
Effects of different types of induced neonatal inflammation on development and behavior of C57BL/6 and BTBR mice
Yuliya A Ryabushkina1, Kseniya A Ayriyants1, Anna A Sapronova1
1Institute of Cytology and Genetics (ICG), Siberian Branch of Russian Academy of Sciences (SB RAS), Prospekt Akad. Lavrentyeva 10, Novosibirsk 630090, Russia.
Insights
Neonatal immune activation (NIA) impacts brain development and mental health. This study found NIA affects neonatal reflexes differently in mouse strains, but shows no delayed effects on social or anxiety behaviors.
Area of Science:
- Neuroscience
- Immunology
- Developmental Biology
Background:
- Early life neuroinflammation can disrupt brain development, potentially leading to later-life mental illnesses.
- Neonatal immune activation (NIA) models are crucial for understanding these developmental impacts.
- The BTBR mouse strain exhibits autism spectrum disorder-like traits and immune dysregulation, making it a relevant model.
Purpose of the Study:
- To evaluate the short- and long-term effects of neonatal inflammation on brain development.
- To compare the susceptibility of C57BL/6 and BTBR mouse strains to neonatal inflammation.
- To investigate the impact of specific inflammatory agents (lipopolysaccharide, poly(I:C)) on neonatal reflexes and later behaviors.
Main Methods:
- Induction of neonatal inflammation using lipopolysaccharide, poly(I:C), or a combination in C57BL/6 and BTBR mice.
- Assessment of neonatal reflexes, including cliff aversion.
- Evaluation of social behavior and anxiety-like behavior in juvenile and adolescent mice.
Main Results:
- BTBR mice demonstrated greater sensitivity to NIA regarding neonatal reflex formation compared to C57BL/6 mice.
- Lipopolysaccharide administration affected cliff aversion reflex in female BTBR mice.
- NIA did not produce delayed effects on social or anxiety-like behaviors in either strain.
Conclusions:
- NIA exerts strain-, age-, and mimetic-dependent effects on neonatal reflex development and exploratory activity.
- While early inflammation impacts neonatal reflexes, long-term behavioral consequences like social deficits or anxiety were not observed in this model.
- The BTBR strain's heightened sensitivity to NIA in reflex development warrants further investigation.
Abstract:
Neuroinflammation in the early postnatal period can disturb trajectories of the completion of normal brain development and can lead to mental illnesses, such as depression, anxiety disorders, and personality disorders later in life. In our study, we focused on evaluating short- and long-term effects of neonatal inflammation induced by lipopolysaccharide, poly(I:C), or their combination in female and male C57BL/6 and BTBR mice. We chose the BTBR strain as potentially more susceptible to neonatal inflammation because these mice have behavioral, neuroanatomical, and physiological features of autism spectrum disorders, an abnormal immune response, and several structural aberrations in the brain. Our results indicated that BTBR mice are more sensitive to the influence of the neonatal immune activation (NIA) on the formation of neonatal reflexes than C57BL/6 mice are. In these experiments, the injection of lipopolysaccharide had an effect on the formation of the cliff aversion reflex in female BTBR mice. Nonetheless, NIA had no delayed effects on either social behavior or anxiety-like behavior in juvenile and adolescent BTBR and C57BL/6 mice. Altogether, our data show that NIA has mimetic-, age-, and strain-dependent effects on the development of neonatal reflexes and on exploratory activity in BTBR and C57BL/6 mice.
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