Strain dependent effects of prenatal stress on gene expression in the rat hippocampus

Multiple animal models have been developed to recapitulate phenotypes of the human disease, schizophrenia. A model that simulates many of the cognitive and sensory deficits of the disorder is the use of random variable prenatal stress (PS) in the rat. These deficits suggest a molecular origin in the hippocampus, a brain region that plays a role in the regulation of stress. To study both hippocampal gene expression changes in offspring of prenatally stressed dams and to address genetic variability, we used a random array of prenatal stressors in three different rat strains with diverse responses to stress: Fischer, Sprague-Dawley, and Lewis rats. Candidate genes involved in stress, schizophrenia, cognition, neurotrophic effects, and immunity were selected for assessment by real-time quantitative PCR under resting conditions and following a brief exposure to restraint stress. PS resulted in significant differences in gene expression in the offspring that were strain dependent. mRNA expression for the N-methyl-D-aspartate receptor subtype 2B (Grin2b) was increased, and tumor necrosis factor-alpha (Tnf alpha) transcript was decreased in PS Sprague-Dawley and Lewis rats, but not in the Fischer rats. Expression of brain-derived neurotrophic factor (Bdnf) mRNA in the hippocampus was increased after an acute stress in all controls of each strain, yet a decrease was seen after acute stress in the PS Sprague-Dawley and Lewis rats. Expression of the glucocorticoid receptor (Nr3c1) was decreased in the Fischer strain when compared to Lewis or Sprague-Dawley rats, though the Fischer rats had markedly higher alpha 7 nicotinic receptor (Chrna7) expression. The expression differences seen in these animals may be important elements of the phenotypic differences seen due to PS and genetic background. Published by Elsevier Inc.