Partial Reelin Deficiency Modulates Behavioral and Prefrontal Effects of Mild Prenatal Poly(I:C) Exposure.

Area of Science:

• Neuroscience
• Psychiatry
• Genetics

Background:

• Gene-environment interactions are crucial for neurodevelopmental psychiatric disorders.
• The precise behavioral and molecular impacts of these interactions are not fully understood.

Purpose of the Study:

• To investigate if partial reelin (Reln) deficiency heightens susceptibility to mild prenatal immune challenges.
• To analyze the behavioral and molecular consequences of this combined genetic and environmental risk in mice.

Main Methods:

• Heterozygous Reln mice and wild-type littermates were exposed to polyinosinic-polycytidylic acid (Poly(I:C)) during prenatal development.
• Adult male offspring underwent behavioral testing (open-field, social interaction, marble-burying).
• Gene expression in the medial prefrontal cortex (mPFC) was analyzed.

Main Results:

• Prenatal Poly(I:C) increased locomotor activity, most notably in the combined-risk group.
• Social novelty preference was impaired in the combined-risk group, though general sociability remained.
• Marble-burying behavior was reduced in Reln-deficient mice, independent of immune exposure.
• Medial prefrontal cortex gene expression showed alterations in GABA_A receptor subunits, with reduced Gabra2 in the combined-risk group and decreased Reln in heterozygous mice.

Conclusions:

• Partial reelin deficiency creates a genetic background that makes mice more vulnerable to subtle behavioral and molecular changes following prenatal immune activation.
• These findings highlight the intricate interplay between genetics and environment in shaping neurodevelopment and behavior.