TY - JOUR
T1 - Longitudinal in vivo maturational changes of metabolites in the prefrontal cortex of rats exposed to polyinosinic-polycytidylic acid in utero
AU - Vernon, Anthony C.
AU - So, Po Wah
AU - Lythgoe, David J.
AU - Chege, Winfred
AU - Cooper, Jonathan D.
AU - Williams, Steven C.R.
AU - Kapur, Shitij
N1 - Publisher Copyright:
© 2015 Elsevier B.V. and ECNP.
PY - 2015/12/1
Y1 - 2015/12/1
N2 - Proton magnetic resonance spectroscopy (1H 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 1H 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 1H 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 1H 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.
AB - Proton magnetic resonance spectroscopy (1H 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 1H 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 1H 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 1H 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.
KW - Glutathione
KW - Magnetic resonance spectroscopy
KW - Maternal immune activation
KW - Poly (I:C)
KW - Schizophrenia
KW - Taurine
UR - http://www.scopus.com/inward/record.url?scp=84952639496&partnerID=8YFLogxK
U2 - 10.1016/j.euroneuro.2015.09.022
DO - 10.1016/j.euroneuro.2015.09.022
M3 - Article
C2 - 26475576
AN - SCOPUS:84952639496
SN - 0924-977X
VL - 25
SP - 2210
EP - 2220
JO - European Neuropsychopharmacology
JF - European Neuropsychopharmacology
IS - 12
ER -