Developmental Alterations in the Transcriptome of Three Distinct Rodent Models of Schizophrenia

Schizophrenia is a debilitating disorder affecting just under 1% of the population. While the symptoms of this disorder do not appear until late adolescence, pathological alterations likely occur earlier, during development in utero. While there is an increasing literature examining transcriptome alterations in patients, it is not possible to examine the changes in gene expression that occur during development in humans that will develop schizophrenia. Here we utilize three distinct rodent developmental disruption models of schizophrenia to examine potential overlapping alterations in the transcriptome, with a specific focus on markers of interneuron development. Specifically, we administered either methylazoxymethanol acetate (MAM), Polyinosinic:polycytidylic acid (Poly I:C), or chronic protein malnutrition, on GD 17 and examined mRNA expression in the developing hippocampus of the offspring 18 hours later. Here, we report alterations in gene expression that may contribute to the pathophysiology of schizophrenia, including significant alterations in interneuron development and ribosome function. Overall design: Timed pregnant female Sprague-Dawley rats were obtained from Envigo on gestational day 11. Either polyinosine:cytosine (Poly I:C, 7.5 mg/kg, i.p), methylazoxymethanol acetate (MAM: 22mg/kg, i.p.) or saline were administered on gestational day 17. For maternal protein malnutrition, pregnant rats had access to a low protein diet ad libitum (Envigo: TD.90016) containing 6.1% protein, 75.6% carbohydrate and 5.5% fat (3.8Kcal/g) from GD11-GD18. Control rats were fed an isocaloric diet of 20.3% protein, 61.6% carbohydrate and 5.5% fat (3.8Kcal/g: Envigo: TD.91352) from GD11-GD18. Experiments included three pups from multiple (two) litters for a total of 6 pups per group.