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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
Region Specific Effects of Maternal Immune Activation on Offspring Neuroimmune Function
1Department of Biological Sciences, Seton Hall University, New Jersey, USA.
Insights
Maternal immune activation during pregnancy alters offspring neuroimmune responses. Prenatal exposure to lipopolysaccharide (LPS) reduced inflammatory gene expression in the offsprings prefrontal cortex, indicating region-specific effects on brain development.
Area of Science:
- Neuroimmunology
- Developmental Neuroscience
- Maternal Immune Activation
Background:
- Maternal immune activation (MIA) influences offspring immune competence.
- Understanding region-specific neuroimmune effects of MIA is crucial.
Purpose of the Study:
- To investigate the region-specific impact of maternal immune activation on offspring neuroimmune function.
- To analyze the effects of prenatal lipopolysaccharide (LPS) exposure on inflammatory gene expression in the developing brain.
Main Methods:
- Maternal treatment with saline or LPS at gestational day 18.
- Offspring stimulation with saline or LPS at postnatal day 21.
- Analysis of inflammatory gene mRNA expression in distinct brain regions (prefrontal cortex, brainstem).
Main Results:
- Offspring from saline-treated dams showed typical inflammatory responses to LPS across brain regions.
- Offspring from LPS-treated dams exhibited attenuated inflammatory gene induction in the prefrontal cortex, but not the brainstem.
- LPS-induced I-κBζ mRNA expression was reduced in the prefrontal cortex of offspring from LPS-treated dams.
Conclusions:
- Maternal LPS exposure has differential effects on neuroimmune function in specific brain regions of offspring.
- The maternal environment plays a critical role in shaping offspring neuroimmune development.
Abstract:
Growing evidence suggests that maternal immune activation has a significant impact on the immuno-competence of the offspring. The present study aimed to characterize region-specific effects of maternal immune activation on the offspring's neuroimmune function. The offspring born to dams treated with saline or lipopolysaccharide (LPS) at gestational day 18 was stimulated with saline or LPS at postnatal day 21, and the mRNA expression of various inflammatory genes in different brain regions of the offspring was analyzed. The offspring born to saline-treated dams exhibited a typical neuroimmune response with elevated levels of cytokines and chemokines following LPS stimulation in all four brain regions examined. In contrast, the offspring born to LPS-treated dams exhibited significantly reduced mRNA induction of cytokines and chemokines following LPS stimulation in the prefrontal cortex but not in the brainstem when compared with pups born to saline-treated dams. Furthermore, the mRNA expression of LPS-induced I-κBζ was significantly attenuated in the prefrontal cortex when compared with pups born to saline-treated dams. These results suggest that maternal LPS may have differential effects on the neuroimmune function in different regions of the offspring brain, and highlight the importance of maternal milieu in the development of neuroimmune function in the offspring.
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