Research reportBrain enlargement and increased behavioral and cytokine reactivity in infant monkeys following acute prenatal endotoxemia

Infections and inflammatory conditions during pregnancy can dysregulate neural development and increase the risk for developing autism and schizophrenia. The following research utilized a nonhuman primate model to investigate the potential impact of a mild endotoxemia during pregnancy on brain maturation and behavioral reactivity as well as the infants' hormone and immune physiology. Nine pregnant female rhesus monkeys (Macaca mulatta) were administered nanogram concentrations of lipopolysaccharide (LPS) on two consecutive days, 6 weeks before term, and their offspring were compared to nine control animals. When tested under arousing challenge conditions, infants from the LPS pregnancies were more behaviorally disturbed, including a failure to show a normal attenuation of startle responses on tests of prepulse inhibition. Examination of their brains at 1 year of age with magnetic resonance imaging (MRI) revealed the unexpected finding of a significant 8.8% increase in global white matter volume distributed across many cortical regions compared to controls. More selective changes in regional gray matter volume and cortical thickness were noted in parietal, medial temporal, and frontal areas. While inhibited neural growth has been described previously after prenatal infection and LPS administration at higher doses in rodents, this low dose endotoxemia in the monkey is the first paradigm to produce a neural phenotype associated with augmented gray and white matter growth.

Research highlights▶ LPS-exposed infants show more white matter in many brain regions at 1 year of age. ▶ More gray matter is also selectively seen in brain regions at 1 year of age. ▶ LPS exposure induces behavioral hyperreactivity and then inhibition over time. ▶ Cytokine and cortisol physiology profiles only change under aversive conditions.