Double trouble: Prenatal immune activation in stress sensitive offspring

Area of Science:

• Neuroscience
• Immunology
• Psychiatry

Background:

• Viral infections in pregnancy are linked to offspring psychiatric disorders.
• Innate immune responses to infection can harm fetal development, leading to adult psychopathology.
• The impact of maternal viral infections on offspring varies significantly.

Purpose of the Study:

• To investigate if differential stress sensitivity influences immune reactivity heterogeneity.
• To explore the role of stress sensitivity in the pathological consequences of maternal immune activation.
• To examine the impact of prenatal viral-like infection on stress-sensitive offspring.

Main Methods:

• Utilized mouse models with innate stress resilience (Dom) and vulnerability (Sub).
• Administered Poly(I:C) (viral analogue) to assess immune reactivity in nulliparous and pregnant females.
• Evaluated offspring behavioral responses to MK-801 (NMDA antagonist).

Main Results:

• Sub females exhibited a heightened pro- and anti-inflammatory cytokine response to Poly(I:C) compared to Dom females.
• Prenatal Poly(I:C) exposure potentiated the enhanced locomotory response in Sub offspring born to Sub mothers.
• Findings suggest inherited stress sensitivity influences glutamatergic signaling, exacerbated by prenatal viral-like infection.

Conclusions:

• Inherited stress sensitivity plays a critical role in modulating maternal immune responses to viral-like stimuli.
• Prenatal exposure to viral-like infections can exacerbate neurodevelopmental alterations in stress-vulnerable offspring.
• The maternal immunome is a key factor in mediating the link between maternal stress sensitivity, immune activation, and offspring psychopathology.