Ex vivo 1H-MRS brain metabolic profiling in a two-hit model of neurodevelopmental disorders: Prenatal immune activation and peripubertal stress

Prenatal infections are environmental risk factors for neurodevelopmental disorders. In addition, trau-matic experiences during adolescence in individuals exposed to infections during gestation could in-crease the risk of schizophrenia. It is of the most crucial importance to discover potential markers of the disease in its early stages or before its onset, so that therapeutic strategies may be implemented. In the present study, we combined a proposed two-hit model of schizophrenia-related symptoms with proton magnetic resonance spectroscopy (1H-MRS) to discover potential biomarkers. To this end, we i.p. injected 100 mg/kg/ml of lipopolysaccharide (LPS) or saline on gestational days 15 and 16 to pregnant rats. Their male offspring were then subjected to five episodes of stress or handling on alternate days during postnatal days (PND) 28-38. Once the animals reached adulthood (PND70), we evaluated prepulse in-hibition (PPI). At PND90, we performed an ex vivo 1H-MRS study in the cortex and striatum. While we did not detect alterations in PPI at the age tested, we found neurochemical disturbances induced by LPS, stress or (more interestingly) their interaction. LPS decreased glucose levels in the cortex and striatum and altered glutamate, glutamine and N-acetylaspartate levels. Glutamate and glutamine levels in the left (but not right) striatum were differentially affected by prenatal LPS exposure in a manner that depended on stress experiences. These results suggest that alterations in the glutamate cycle in the striatum could be used as early markers of developmental disorders. (C) 2019 Elsevier B.V. All rights reserved.

Automated summary

Prenatal infections and traumatic experiences during adolescence may increase the risk of schizophrenia. Using proton magnetic resonance spectroscopy, this study found that alterations in the glutamate cycle in the striatum could serve as potential markers of developmental disorders in the early stages or before the onset of the disease.