Regional brain network and behavioral alterations in EGR3 gene transfected rat model of schizophrenia

Abstract

Schizophrenia is a severe psychiatric disease while its etiology and effective treatment are not completely clear. A rat model of schizophrenia was previously established by transfecting EGR3 gene into the hippocampus of rats. This study aimed to investigate the behavioral and cerebral alterations of the schizophrenic model rats and the risperidone effects. Twenty-six rats were divided into 3 groups: schizophrenia model group (E group), risperidone treatment group (T group), and healthy control group (H group). Morris water maze and open field test were used as behavioral tests, resting-state functional magnetic resonance imaging (fMRI) was performed after EGR3 gene transfection and risperidone therapy. Graph analyses were used for examining cerebral alterations of the rats. Behavioral tests demonstrated reduced spatial working memory and exploring unfamiliar space ability in schizophrenic model rats. Graph analyses revealed reduced regional architectures in the olfactory bulb, nucleus accumbens, and pineal gland in group E compared to group H (p < 0.05), while group T showed increased regional architecture in pineal gland compared to group E (p < 0.05). Besides, the regional architectures in the olfactory bulb, nucleus accumbens were lower in group T than group H, while the hippocampus showed increased regional architecture in group T compared to group H (p < 0.05). Schizophrenia induced several regional alterations in the cerebrum while risperidone can reverse part of these alterations. This study lends support for future research on the pathology of schizophrenia and provides new insights on the role of risperidone in schizophrenia.

Keywords: Behavioral test; Graph analysis; Resting‐state fMRI; Risperidone; Schizophrenia.