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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
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Gestational diabetes exacerbates maternal immune activation effects in the developing brain
K M Money1,2, T L Barke3,4, A Serezani5
1Neuroscience Graduate Program, Vanderbilt University, Nashville, TN, USA.
Molecular Psychiatry
|September 27, 2017
Summary
Maternal diabetes and inflammation together worsen fetal brain development, increasing offspring risk for psychiatric disorders. This combined exposure triggers specific gene expression changes linked to neurodevelopmental pathways.
Area of Science:
- Neuroscience
- Developmental Biology
- Psychiatry
Background:
- Maternal diabetes and inflammation are known risk factors for offspring psychiatric disorders.
- The combined effects of these risk factors on fetal brain development are not fully understood.
Purpose of the Study:
- To investigate the potentiating effects of gestational diabetes mellitus (GDM) and maternal immune activation (MIA) on fetal brain development.
- To identify specific molecular pathways altered by combined GDM and MIA exposure.
Main Methods:
- Mice were exposed in utero to vehicle, GDM, MIA, or combined GDM+MIA.
- Transcriptome profiling of fetal mouse brains was performed at gestational day 12.5.
Main Results:
- Both GDM and MIA alone altered fetal brain gene expression, impacting inflammatory and neurodevelopmental pathways.
- Combined GDM+MIA exacerbated the maternal inflammatory state and induced a unique transcriptional response in fetal brains.
- This exacerbated response involved pathways critical for dopamine neuron differentiation and innate immune response, implicated in psychiatric disorders.
Conclusions:
- Combined maternal GDM and MIA exposure synergistically impacts fetal brain development.
- This synergistic effect increases offspring vulnerability to psychiatric disorders.
- Further epidemiological studies are warranted to confirm these findings in human populations.
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