The Effect of an Environmental Stimulus on a Genetic Pathway Associated with Schizophrenia

Schizophrenia risk is influenced by both genetic and environmental factors. The immediate early gene early growth response 3 (Egr3), is regulated downstream of several schizophrenia risk genes and encodes a zinc-finger transcription factor protein. Previous studies from our lab indicate that Egr3 deficient (Egr3 -/-) mice exhibit schizophrenia-like phenotypes. We also discovered decreased serotonin 2a receptors (5-HT2AR) in the Egr3 -/- mice, similar to studies that reported decreased 5-HT2ARs in schizophrenia patients. We previously reported that sleep deprivation, a mild stress, causes the over expression of Egr3 and the serotonin 2a gene (Htr2a) in the cortex. To determine whether EGR3, a transcription factor, regulates Htr2a in the prefrontal cortex after sleep deprivation, Egr3 -/-and Egr3 +/+ mice were sleep deprived for eight hours. Transgenic mice were used that expressed enhanced green fluorescent protein (EGFP) under control of the Htr2a promoter via a bacterial artificial chromosome (BAC). Immunohistochemistry was performed to identify EGFP containing cells. Data analysis revealed no significant interaction between genotype and sleep deprivation in 5-HT2AR/EGFP containing cells within the prefrontal cortex. Based on the findings of this study, more data is needed to better determine the relationship between sleep deprivation and its effect on the regulation of Htr2a through in an EGR3 dependent manner.