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Induction of Maternal Immune Activation in Mice at Mid-gestation Stage with Viral Mimic Poly(I:C)
Published on: March 25, 2016
Prenatal immune activation induces maturation-dependent alterations in the prefrontal GABAergic transcriptome
Juliet Richetto1, Francesca Calabrese, Marco A Riva
1*To whom correspondence should be addressed; tel: +41 44 655 7403, fax: +41 44 655 7203,
Schizophrenia Bulletin
|January 19, 2013
Summary
Prenatal immune activation, induced by poly(I:C), alters GABAergic gene expression in the prefrontal cortex, leading to working memory deficits in adult mice. These changes highlight the long-term impact of prenatal infections on brain development and neuropsychiatric disorders.
Area of Science:
- Neuroscience
- Developmental Neuroscience
- Molecular Psychiatry
Background:
- Cortical GABAergic system dysfunction is linked to neuropsychiatric disorders with prenatal infectious origins, such as schizophrenia.
- Transcriptional impairments in the GABAergic system may underlie these abnormalities.
- The long-term effects of prenatal immune challenges on GABAergic gene transcription are not fully understood.
Purpose of the Study:
- To investigate how prenatal immune activation affects GABAergic gene expression and function in the developing brain.
- To determine if prenatal immune challenge leads to long-term alterations in the prefrontal cortex's GABAergic system.
- To explore the relationship between these alterations and cognitive deficits.
Main Methods:
- Utilized a mouse model of prenatal immune activation via maternal gestational administration of poly(I:C) (a viral mimetic).
- Analyzed mRNA expression of key GABAergic genes (GAD65, GAD67, VGAT, GABA(A) receptor subunits, chloride transporters) in the prefrontal cortex.
- Confirmed protein expression levels of GAD65/GAD67 and VGAT using Western blot analysis.
- Assessed working memory function in offspring at different developmental stages.
Main Results:
- Prenatal immune activation induced maturation-dependent alterations in prefrontal GABAergic gene expression.
- Affected genes included those involved in GABA biosynthesis, transport, and receptor function.
- Protein levels of GAD65/GAD67 and VGAT were reduced.
- GABAergic transcriptome alterations were more pronounced in adult offspring, coinciding with the onset of working memory deficiency.
Conclusions:
- Prenatal immune insults significantly impact the long-term GABAergic system in the brain.
- These changes are age-dependent, with more severe effects observed in adulthood.
- The findings underscore the critical role of prenatal immune challenges in the etiology of neuropsychiatric disorders with delayed onset.
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