Prenatal exposure to high- but not low-molecular-weight poly(I:C) produces selective sociability deficits in...

Area of Science:

• Neuroscience
• Developmental Biology
• Immunology

Background:

• Maternal immune activation (MIA) models are used to study prenatal inflammation's impact on autism spectrum disorder (ASD).
• The immune response to polyinosinic:polycytidylic acid (poly(I:C)) varies with its molecular weight.
• Poly(I:C) molecular composition may influence the development of social deficits in offspring.

Purpose of the Study:

• To investigate if the molecular weight of poly(I:C) affects social behavior deficits in offspring following MIA.
• To determine if high-molecular-weight (HMW) or low-molecular-weight (LMW) poly(I:C) is a more valid model for ASD-associated prenatal immune challenges.

Main Methods:

• Pregnant Wistar rats were injected with HMW or LMW poly(I:C) on gestational day 14.
• Offspring were assessed for social behavior (homing response, social interaction) and general activity (open field, elevated plus maze).
• Data were analyzed using nested linear mixed models.

Main Results:

• HMW poly(I:C) significantly impaired neonatal homing responses and adult social investigation in both sexes.
• HMW-exposed males showed increased social approach, while both HMW- and LMW-exposed males exhibited hyperlocomotion.
• Only HMW poly(I:C) exposure led to robust deficits in early social communication and adult social behavior.

Conclusions:

• The molecular weight of poly(I:C) is a critical determinant of MIA model outcomes.
• HMW poly(I:C) is a more reliable and translationally valid preparation for modeling ASD-associated prenatal immune challenges.
• Prenatal exposure to HMW poly(I:C) induces significant and lasting social deficits in offspring.