Activation of the maternal immune system during pregnancy alters behavioral development of rhesus monkey offspring

Biological Psychiatry
Melissa D BaumanPaul H Patterson

Abstract

Maternal infection during pregnancy is associated with an increased risk of schizophrenia and autism in the offspring. Supporting this correlation, experimentally activating the maternal immune system during pregnancy in rodents produces offspring with abnormal brain and behavioral development. We have developed a nonhuman primate model to bridge the gap between clinical populations and rodent models of maternal immune activation (MIA). A modified form of the viral mimic, synthetic double-stranded RNA (polyinosinic:polycytidylic acid stabilized with poly-L-lysine) was delivered to two separate groups of pregnant rhesus monkeys to induce MIA: 1) late first trimester MIA (n = 6), and 2) late second trimester MIA (n = 7). Control animals (n = 11) received saline injections at the same first or second trimester time points or were untreated. Sickness behavior, temperature, and cytokine profiles of the pregnant monkeys confirmed a strong inflammatory response to MIA. Behavioral development of the offspring was studied for 24 months. Following weaning at 6 months of age, MIA offspring exhibited abnormal responses to separation from their mothers. As the animals matured, MIA offspring displayed increased repetitive behaviors and decre...Continue Reading

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Related Concepts

Immune System
Poly ICLC
Behavior, Animal
Pregnancy Complications, Infectious
MIA2 gene
Nonhuman primate
Schizophrenia
Phenylketonuria, Maternal
Poly-(Alpha-L-Lysine)
RNA, Double-Stranded

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