Influence of EGR3 Transfection on Imaging and Behavior in Rats and Therapeutic Effect of Risperidone in Schizophrenia Model

Schizophrenia is a type of neurodevelopmental psychiatric disorder. However, to date, scientists have not discovered the etiology and effective treatment of this condition. We injected the early growth response gene (EGR3) into the bilateral hippocampus to build a schizophrenia rat model. Behavioral phenotyping and resting-state functional magnetic resonance imaging (rs-fMRI) were used to analyze the behavioral and cerebral alterations in the schizophrenia rat model. The efficacy of risperidone therapy was also evaluated. We divided 34 rats into four groups: schizophrenia model group (E group), sham-operation group (FE group), healthy control group (H group), and risperidone therapy group (T group). Open field test and Morris water maze were conducted as behavioral experiments. Next, we performed rs-fMRI after four weeks of EGR3 transfection and risperidone treatment and analyzed imaging data using regional homogeneity (ReHo), the amplitude of low-frequency fluctuations (ALFF), and functional connectivity (FC). We examined the difference in behavioral and neural activation among the four groups and considered the correlations between behavior and imaging results. EGR3 gene transfection decreased the total moved distance in the open field test and the duration in the Q5 zone of the Morris water maze. Risperidone treatment reversed the trend and improved the performance of rats in these behavioral tests. Schizophrenia induced several neural alterations in ALFF and ReHo metrics of the rat brain, and risperidone could partly reverse these alterations. The results suggest that similar research is required for schizophrenia and that risperidone may be a novel treatment for dysregulated neural activation in schizophrenia.