Irreversible Primary Visual Cortex Impairment in a Mouse Model of High-Risk Schizophrenia

Abstract

Xinying Chen,1,* Ce Chen,2,* Feng Ji,3,* Yong Xu,4 Wenqiang Wang,5 Xiaodong Lin,2 Deguo Jiang,2 Xueqin Song,6 Xiangyang Gao,7 Hongjun Tian,8 Chuanjun Zhuo,8 Jingliang Zhang9 1Psychiatric-Neuroimaging-Genetics-Comorbidity Laboratory (PNGC_Lab), Tianjin Mental Health Centre, Mental Health Teaching Hospital of Tianjin Medical University, Tianjin Anding Hospital, Tianjin 300222, People’s Republic of China; 2Psychiatric-Neuroimaging-Genetics Laboratory, Wenzhou Seventh People’s Hospital, Wenzhou, Zhejiang Province 325000, People’s Republic of China; 3Department of Psychiatry, School of Mental Health, Jining Medical University, Jining 272119, Shandong Province, People’s Republic of China; 4Department of Psychiatry, First Hospital/First Clinical Medical College of Shanxi Medical University, MDT Center for Cognitive Impairment and Sleep Disorders, First Hospital of Shanxi Medical University, Taiyuan 030001, People’s Republic of China; 5Co-Collaboration Laboratory of China and Canada, Xiamen Xianyue Hospital and University of Alberta, Xiamen 361000, People’s Republic of China; 6The First Affiliated Hospital/Zhengzhou University, Biological Psychiatry International Joint Laboratory of Henan/Zhengzhou University, Henan Psychiatric Transformation Research Key Laboratory/Zhengzhou University, Zhengzhou 450052, People’s Republic of China; 7Health Management Institute, Center for Statistical Analysis of Medical Data, Medical Big Data Analysis Center, Chinese PLA General Hospital, Beijing 100191, People’s Republic of China; 8Department of Neurology and Psychiatry Biological Imaging Laboratory (NPBI_Lab), Tianjin Fourth Center Hospital, Tianjin 200024, People’s Republic of China; 9Department of Psychiatry, Wenzhou Kangning Hospital, Wenzhou, Zhejiang Province 325007, People’s Republic of China*These authors contributed equally to this workCorrespondence: Chuanjun ZhuoDepartment of Neurology and Psychiatry Biological Imaging Laboratory (NPBI_Lab), Tianjin Fourth Center Hospital, Tianjin 200024, People’s Republic of ChinaTel/Fax [phone]Email [email protected] ZhangDepartment of Psychiatry, Wenzhou Kangning Hospital, Wenzhou, Zhejiang Province 325007, People’s Republic of ChinaEmail [email protected]: Although visual deficits can be observed at any stage of schizophrenia, few studies have focused on visual cortex alterations in individuals at high risk of schizophrenia. This study aimed to investigate the pathological changes of the primary visual cortex in a prenatal mouse model of MK801-induced high-risk schizophrenia.Methods: The high-risk schizophrenia model was generated by MK801 injection into pregnant mice. The male offspring without schizophrenia-like behaviors in early adulthood were defined as the high-risk mouse model of schizophrenia (HRMMS) and divided into two groups. One HRMMS group received the antipsychotic agent risperidone beginning at postnatal week 4 and another group did not receive any treatment. After treatment for 4 weeks, in vivo two-photon calcium imaging was performed to characterize the primary visual cortex activity. The novel object recognition test and the prepulse inhibition apparatus test were also implemented to assess the cognitive and behavioral performance, respectively.Results: Both groups of HRMMS mice, with or without antipsychotic treatment, had decreased neuronal calcium activity, demonstrating primary visual cortex impairment. More notably, antipsychotic treatment did not normalize the impaired neuronal activities in the primary visual cortex. Correspondingly, the treatment did not improve the cognitive or behavioral impairment.Conclusion: Visual cortex impairment might be a prominent feature of individuals at high risk of schizophrenia that cannot be normalized by early treatment with antipsychotic medication, indicating the presence of independent regulatory pathways for visual perception disturbance in schizophrenia. Thus, visual system impairment in schizophrenic patients must be further studied.Keywords: schizophrenia, animal model, primary visual cortex, antipsychotics

Keywords

• schizophrenia
• animal model
• primary visual cortex
• antipsychotics