Basolateral amygdala Rims1 mediates adolescent social isolation-induced schizophrenia-like behaviors in mice

Abstract

Abstract Schizophrenia (SCZ) is a common and debilitating mental illness that severely affects the quality of life of patients and their families. Due to the diversity, intensity and complexity of its symptoms, this disorder is poorly understood, diagnosed and treated. Genetic and chemical exposure factors are widely accepted to cause schizophrenia until now. However, little is known about whether and how single environmental factor itself can lead to schizophrenia. In this study, by using Mendelian randomization analysis (MR), we found that social isolation was an etiologic factor in the development of schizophrenia. Furthermore, we interestingly found that five-week social isolation immediately after weaning induced schizophrenia-like behaviors, which met the principle of the etiologic validity, face validity and predictive validity in establishing a mouse model of schizophrenia. Meanwhile, summary data-based Mendelian randomization analysis (SMR) indicated that Rab-3 interacting molecule-1 (Rims1) was a susceptibility gene for schizophrenia. Adolescent social isolation-induced schizophrenia-like behaviors was accompanied by decreased level of Rims1 in the basolateral amygdala (BLA). And knockdown of Rims1 facilitated social isolation-induced schizophrenia-like behaviors. Finally, disturbed excitatory synaptic neurotransmission was critically involved in social isolation-induced schizophrenia-like behaviors. Our findings thus establish a new animal model in studying the mechanisms of schizophrenia and offer a potential method for analyzing the interactive effects of individual genetic and environmental factors in the onset and development of schizophrenia.