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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
Prenatal Poly I:C Challenge Affects Behaviors and Neurotransmission via Elevated Neuroinflammation Responses in
Yueqing Su1,2,3,4, Jiamei Lian4, James Hodgson3,4
1The School of Public Health, Fujian Medical University, Fuzhou, China.
Insights
Maternal exposure to polyriboinosinic-polyribocytidylic acid (Poly I:C) during pregnancy induced anxiety, depression, and cognitive changes in adolescent female rats. These behavioral alterations were linked to neuroinflammation and altered neurotransmitter receptor expression.
Area of Science:
- Neuroscience
- Developmental Psychology
- Immunology
Background:
- Maternal immune activation via polyriboinosinic-polyribocytidylic acid (Poly I:C) exposure in rats is linked to schizophrenia-like behaviors in adult male offspring.
- The impact of prenatal Poly I:C exposure on adolescent female rat behaviors and neurotransmission remains less understood.
Purpose of the Study:
- To investigate the behavioral and neurobiological effects of maternal Poly I:C exposure on adolescent female rats.
- To examine changes in neurotransmitter receptors and neuroinflammation markers in the brains of female offspring following prenatal Poly I:C exposure.
Main Methods:
- Female offspring were generated from timed pregnant rats injected with Poly I:C on gestation day 15.
- Behavioral tests including open field, elevated plus maze, forced swimming, pre-pulse inhibition, social interaction, and novel object recognition were conducted from postnatal day 35-60.
- Neurotransmitter receptor and inflammation marker expression in brain regions were assessed using RT-qPCR on postnatal day 60.
Main Results:
- Prenatal Poly I:C exposure induced anxiety-like and depression-like behaviors, alongside deficits in pre-pulse inhibition and social interaction in female adolescent rats.
- Cognitive function appeared improved, evidenced by enhanced performance in the novel object recognition test.
- Neuroinflammation markers (P2X7 receptor, NF-κB-NLRP3-IL-1β pathway) were elevated in specific brain regions.
- Expression of GABAA and dopamine D2 receptors decreased in certain brain areas, while NMDA and 5-HT2A receptor expression increased in others.
Conclusions:
- Prenatal Poly I:C exposure in rats leads to significant behavioral alterations in adolescent female offspring.
- These behavioral changes are associated with region-specific alterations in neurotransmission and heightened neuroinflammation.
- The findings highlight the vulnerability of the developing female brain to maternal immune challenges.
Background:
Exposure to polyriboinosinic-polyribocytidylic acid (Poly I:C) in pregnant rats has been reported to cause schizophrenia-like behaviors and abnormal neurotransmissions in adult, particularly male, offspring. However, what is less well understood are the effects of maternal Poly I:C exposure on adolescent behaviors and neurotransmission in female juvenile rats.
Methods:
Female adolescent Poly I:C offspring were constructed by treating with 5 mg/kg Poly I:C on timed pregnant rats (gestation day 15). A battery of behavioral tests was conducted during postnatal day 35-60. Neurotransmitter receptors and inflammation markers in brain regions were evaluated by RT-qPCR on postnatal day 60.
Results:
Open field, elevated plus maze, and forced swimming tests revealed that prenatal Poly I:C exposure led to elevated anxiety-like and depression-like behaviors in female adolescent offspring. Deficits in pre-pulse inhibition and social interaction were also observed. However, the Poly I:C rats had better performance than the controls in the novel object recognition memory test, which demonstrated a behavioral phenotype with improved cognitive function. Prenatal Poly I:C exposure caused brain region-specific elevation of the P2X7 receptor- and NF-κB-NLRP3-IL-1β inflammatory signaling in female juvenile rats. Prenatal Poly I:C exposure decreased expression of GABAA receptor subunits Gabrb3 in the prefrontal cortex and Gabrb1 and dopamine D2 receptor in the hippocampus, but increased NMDA receptor subunit Grin2a in the prefrontal cortex, 5-HT2A in the hippocampus, and Gabrb3 and D2 receptor in the nucleus accumben.
Conclusions:
Prenatal Poly I:C challenge causes behavioral deficits and brain-specific neurotransmission changes via elevated neuroinflammation responses in female adolescent offspring rats.

