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

Melissa D Bauman, Ana-Maria Iosif, Stephen E P Smith, Catherine Bregere, David G Amaral, Paul H. Patterson

Research output: Contribution to journalArticle

132 Citations (Scopus)

Abstract

Background 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). Methods 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. Results 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 decreased affiliative vocalizations. When evaluated with unfamiliar conspecifics, first trimester MIA offspring deviated from species-typical macaque social behavior by inappropriately approaching and remaining in immediate proximity of an unfamiliar animal. Conclusions In this rhesus monkey model, MIA yields offspring with abnormal repetitive behaviors, communication, and social interactions. These results extended the findings in rodent MIA models to more human-like behaviors resembling those in both autism and schizophrenia.

Original languageEnglish (US)
Pages (from-to)332-341
Number of pages10
JournalBiological Psychiatry
Volume75
Issue number4
DOIs
StatePublished - Feb 15 2014

Fingerprint

Macaca mulatta
Immune System
Mothers
Pregnancy
First Pregnancy Trimester
Rodentia
Second Pregnancy Trimester
Autistic Disorder
Schizophrenia
Illness Behavior
Poly I-C
Double-Stranded RNA
Social Behavior
Maternal Age
Macaca
Interpersonal Relations
Weaning
Primates
Lysine
Haplorhini

Keywords

  • Animal model
  • autism spectrum disorder
  • immune activation
  • macaque
  • nonhuman primate
  • poly IC
  • schizophrenia

ASJC Scopus subject areas

  • Biological Psychiatry

Cite this

Activation of the maternal immune system during pregnancy alters behavioral development of rhesus monkey offspring. / Bauman, Melissa D; Iosif, Ana-Maria; Smith, Stephen E P; Bregere, Catherine; Amaral, David G; Patterson, Paul H.

In: Biological Psychiatry, Vol. 75, No. 4, 15.02.2014, p. 332-341.

Research output: Contribution to journalArticle

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