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

Behav Brain Res. 2011 May 16;219(1):108-15. doi: 10.1016/j.bbr.2010.12.023. Epub 2010 Dec 27.

Abstract

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.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Aging / psychology
  • Animals
  • Anxiety / psychology
  • Attention / drug effects
  • Behavior, Animal / drug effects*
  • Brain / anatomy & histology
  • Brain / drug effects
  • Brain / growth & development*
  • Cerebral Cortex / drug effects
  • Cerebral Cortex / growth & development
  • Cytokines / metabolism*
  • Emotions / drug effects
  • Endotoxemia / psychology*
  • Female
  • Humans
  • Hydrocortisone / metabolism
  • Image Processing, Computer-Assisted
  • Immune System / drug effects
  • Injections, Intraventricular
  • Interleukin-6 / metabolism
  • Interpersonal Relations
  • Lipopolysaccharides / administration & dosage
  • Lipopolysaccharides / pharmacology
  • Macaca mulatta
  • Magnetic Resonance Imaging
  • Neurosecretory Systems / drug effects
  • Neurosecretory Systems / metabolism
  • Pregnancy
  • Prenatal Exposure Delayed Effects / chemically induced
  • Prenatal Exposure Delayed Effects / pathology*
  • Prenatal Exposure Delayed Effects / psychology
  • Reflex, Startle / physiology

Substances

  • Cytokines
  • Interleukin-6
  • Lipopolysaccharides
  • Hydrocortisone