The reduction of volume and fiber bundle connections in the hippocampus of EGR3 transgenic schizophrenia rats

Abstract

Ensen Ma,1,2,* Tianbin Song,3,* Hui Zhang,4,* Jie Lu,5 Liwen Wang,2 Qichao Zhao,2 Runcai Guo,2 Miao Li,2 Guolin Ma,2 Guangming Lu,1 Kefeng Li6,7 1Department of Medical Imaging, Jinling Hospital, Medical School of Nanjing University, Nanjing, People’s Republic of China; 2Department of Radiology, China-Japan Friendship Hospital, Beijing, People’s Republic of China; 3Department of Radiology, Beijing Shunyi Hospital, Beijing, People’s Republic of China; 4Department of Radiology, First Clinical Medical College, Shanxi Medical University, Taiyuan, People’s Republic of China; 5Department of Radiology, Xuanwu Hospital of Capital Medical University, Xicheng, Beijing, People’s Republic of China; 6School of Medicine, University of California, San Diego, CA, USA; 7Tianjin SunnyPeak Biotech Co., Ltd, Tianjin, People’s Republic of China *These authors contributed equally to this work Background and objective: There is a growing consensus that schizophrenia is ultimately caused by abnormal communication between spatially disparate brain structures. White matter fasciculi represent the primary infrastructure for long distance communication in the brain. In this study, we aimed to investigate the white matter connection in schizophrenia susceptible brain regions of early growth response factor 3 (EGR3) expressing rats.Methods: A rat model of schizophrenia was created by the transfection of the EGR3 gene into rat hippocampus. All animals were placed in a fixation system using a commercial rat-dedicated coil. Schizophrenia susceptible brain regions were scanned using in vivo diffusion tensor magnetic resonance imaging. The volume, quantity, average length of fiber bundles, fractional anisotropy, apparent diffusion coefficient, the relative heterosexual fraction, and volume ratio were collected in the whole brain and schizophrenia related brain areas (the hippocampus, thalamus, and prefrontal lobe). MedINRIA software was used for data processing of diffusion tensor and fiber bundles tracking. The fibronectin in relevant brain regions was also analyzed.Results: There was a significant decrease in the volume of the fiber beam through the left hippocampus dentate in the schizophrenia model group in comparison to the control group and the risperidone treatment group (P<0.05). A significant reduction in the volume and number of the fiber bundles was also observed in left prefrontal–left hippocampus, left hippocampus–left thalamus, left prefrontal–left hippocampus–left thalamus areas in the model group (all P<0.05).Conclusion: The volume of hippocampus and the number of fiber bundles were reduced in EGR3 transgenic schizophrenia rats, and are the most sensitive indicators in schizophrenia. The diffusion tensor imaging technique plays an important role in the evaluation of patients with schizophrenia. Keywords: magnetic resonance imaging, schizophrenia, early growth response factor 3, fractional anisotropy, diffusion tensor imaging