Brain kynurenines are modulated in a sex-specific manner in periadolescent rats exposed to poly I:C in utero

• Published in: Brain, behavior, and immunity behavior, and immunity, 2015-10, Vol.49, p.e21-e21
• Main Authors: Vaughn, C.N, Soroka, J.A, Tonelli, L.H
• Format: Article
• Language: English
• Subjects: Allergy and Immunology; Psychiatry
• ISSN: 0889-1591; 1090-2139
• DOI: 10.1016/j.bbi.2015.06.090

Maternal immune activation (MIA) during pregnancy has been shown to be a significant risk factor associated with neurodevelopmental psychiatric disorders in offspring. Kynurenines, in particular kynurenic acid (KYNA, an NMDA receptor antagonist), have been shown to be elevated in the brains of individuals diagnosed with schizophrenia. In the present study, we employed the model of maternal immune activation by use of the viral mimetic agent polyinosinic:polycytidylic acid (poly I:C) in rats (embryonic day 11) to study the regulation of brain kynurenines to a secondary poly I:C challenge (“second hit”) during the periadolescent period of development (postnatal day 35). Basal KYNA levels in the cerebral cortex of rats exposed to poly I:C in utero were elevated in males, but reduced in females. However, administration of poly I:C secondarily in these animals modified KYNA levels in males, but not in females. In addition, kynurenine (Kyn) formation (the precursor of KYNA) was reduced in females without changes in males in basal conditions, while it was increased in both males and females after poly I:C challenge. These results suggest that brain kynurenines are affected by MIA in a sex-dependent manner, with males recapitulating increased KYNA levels in basal conditions as found in people with schizophrenia. The present study highlights the major role played by sex in determining the functional maturation of neurochemical systems affected by inflammatory conditions during pregnancy.