• Cognition Following Prenatal Stress and/or Disruption of Neuregulin-1 Gene; Implications for Schizophrenia

      Taylor, Adam Ryan; Koenig, James I. (2011)
      Schizophrenia is a severe, chronic and disablilitating disease, affecting nearly one percent of the population. Symptoms consist of positive (hallucination, delusions), negative (anhedonia, social withdrawal) and cognitive (memory impairments, attentional deficits). Cognitive symptoms are considered to be a core feature, and contribute greatly to loss of function. Environmental insults, such as prenatal stress, have been shown to increase risk for schizophrenia. In addition, genetic studies have shown that certain genes, such as Neuregulin-1 (NRG1), are consistently associated with schizophrenia. Interactions between genetic vulnerabilities and environmental factors are also considered to be important in the development of schizophrenia. Here, using an animal model of repeated variable prenatal stress (RVPS), we have shown that animals exposed to RVPS have deficits in spatial learning and memory in the Morris water maze, deficits in working memory in a spatial/visual object discrimination task, and long-term memory deficits. Utilizing a rat preparation with disruption of the neuregulin-1 gene, which leads to decreased NRG1 mRNA and protein in the brain, we have found no deficit in the spatial learning version of the Morris water maze, but we do see learning impairments in a discrimination task with both visual and spatial components. Finally, we were not able to show a substantial effect of a gene X environment interaction between RVPS and Nrg1 disruption. Our results indicate that both prenatal stress and disruption of the neuregulin-1 gene, each risk factors for schizophrenia, result in specific deficits in learning and memory. These deficits are also similar to some cognitive impairments in schizophrenia, indicating our manipulations may be a factor in those symptoms of the disease.