Longitudinal in vivo maturational changes of metabolites in the prefrontal cortex of rats exposed to polyinosinic-polycytidylic acid in utero

Eur Neuropsychopharmacol. 2015 Dec;25(12):2210-20. doi: 10.1016/j.euroneuro.2015.09.022. Epub 2015 Oct 21.


Proton magnetic resonance spectroscopy ((1)H MRS) studies in schizophrenia patients generally report decreased levels of N-acetyl-aspartate (NAA), glutamate and glutathione, particularly in frontal cortex. However, these data are inconsistent in part due to confounds associated with clinical samples. The lack of validated diagnostic biomarkers also hampers analysis of the neurodevelopmental trajectory of neurochemical abnormalities. Rodent models are powerful tools to address these issues, particularly when combined with (1)H MRS (clinically comparable technology). We investigated the trajectory of metabolic changes in the prefrontal cortex during brain maturation from adolescence to adulthood in vivo using (1)H MRS in rats exposed prenatally to polyinosinic-polycytidylic acid (POL), a rodent model of maternal immune activation (MIA), an epidemiological risk factor for several psychiatric disorders with a neurodevelopmental origin. Longitudinal in vivo (1)H MRS revealed a significant decrease in PFC levels of GSH and taurine in adult, but not adolescent rats. Significant age×MIA interactions for PFC levels of NAA were also observed. These data replicate some deficits observed in the PFC of patients with schizophrenia. There were no significant changes in the levels of glutamate or any other metabolite. These data suggest prenatal exposure to POL leads to subtle metabolic perturbations of the normal maturing PFC, which may be related to subsequent behavioural abnormalities. Further work is however required to examine any potential confound of shipping stress on the presumed imbalances in PFC metabolites in POL-exposed offspring. Testing the interactions between MIA with stress or genetic risk variants will also be an important advance.

Keywords: Glutathione; Magnetic resonance spectroscopy; Maternal immune activation; Poly (I:C); Schizophrenia; Taurine.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Age Factors
  • Animals
  • Aspartic Acid / analogs & derivatives*
  • Aspartic Acid / metabolism
  • Female
  • Gestational Age
  • Glutamic Acid
  • Glutathione / metabolism*
  • Interferon Inducers / toxicity*
  • Longitudinal Studies
  • Magnetic Resonance Imaging
  • Magnetic Resonance Spectroscopy
  • Male
  • Poly I-C / toxicity*
  • Prefrontal Cortex / metabolism*
  • Prefrontal Cortex / pathology
  • Pregnancy
  • Prenatal Exposure Delayed Effects* / chemically induced
  • Prenatal Exposure Delayed Effects* / pathology
  • Prenatal Exposure Delayed Effects* / physiopathology
  • Protons
  • Rats
  • Rats, Sprague-Dawley
  • Recognition, Psychology / drug effects
  • Taurine / metabolism


  • Interferon Inducers
  • Protons
  • Taurine
  • Aspartic Acid
  • Glutamic Acid
  • N-acetylaspartate
  • Glutathione
  • Poly I-C