Kim, Soojin Kim, Seong-Wook Bui, Mai Anh Thi Kim, Yeji Kim, Minsoo Park, Jung-Cheol Kim, Nam-Heon Pyeon, Gyeong Hee Jo, Yong Sang Jang, Jaewon Koh, Hae-Young Jeong, Chae-Hong Kang, Moonkyung Kang, Hyo Jung Lee, Yong-Woo Stockmeier, Craig A. Seong, Je Kyung Woo, Dong Ho Han, Jung-Soo Kim, Yeon-Soo 2024-01-19T10:32:11Z 2024-01-19T10:32:11Z 2023-04-06 2022-12 0027-8424 https://pubs.kist.re.kr/handle/201004/114199 The selenium-binding protein 1 (SELENBP1) has been reported to be up-regulated in the prefrontal cortex (PFC) of schizophrenia patients in postmortem reports. However, no causative link between SELENBP1 and schizophrenia has yet been established. Here, we provide evidence linking the upregulation of SELENBP1 in the PFC of mice with the negative symptoms of schizophrenia. We verified the levels of SELENBP1 transcripts in postmortem PFC brain tissues from patients with schizophrenia and matched healthy controls. We also generated transgenic mice expressing human SELENBP1 (hSELENBP1 Tg) and examined their neuropathological features, intrinsic firing properties of PFC 2/3-layer pyramidal neurons, and frontal cortex (FC) electroencephalographic (EEG) responses to auditory stimuli. Schizophrenia-like behaviors in hSELENBP1 Tg mice and mice expressing Selenbp1 in the FC were assessed. SELENBP1 transcript levels were higher in the brains of patients with schizophrenia than in those of matched healthy controls. The hSELENBP1 Tg mice displayed negative endophenotype behaviors, including heterotopias- and ectopias-like anatomical deformities in upper-layer cortical neurons and social withdrawal, deficits in nesting, and anhedonia-like behavior. Additionally, hSELENBP1 Tg mice exhibited reduced excitabilities of PFC 2/3-layer pyramidal neurons and abnormalities in EEG biomarkers observed in schizophrenia. Furthermore, mice overexpressing Selenbp1 in FC showed deficits in sociability. These results suggest that upregulation of SELENBP1 in the PFC causes asociality, a negative symptom of schizophrenia. English National Academy of Sciences SELENBP1 overexpression in the prefrontal cortex underlies negative symptoms of schizophrenia Article 10.1073/pnas.2203711119 1 Proceedings of the National Academy of Sciences of the United States of America, v.119, no.51 Proceedings of the National Academy of Sciences of the United States of America 119 51 Y scie scopus 000944703500002 2-s2.0-85144393190 Multidisciplinary Sciences Science & Technology - Other Topics Article FRONTAL-LOBE PATHOLOGY COPY NUMBER VARIATION GRAY-MATTER VOLUME SOCIAL-INTERACTION GENE-EXPRESSION ENDOPHENOTYPES BEHAVIOR STRESS MODEL MIND SELENBP1 schizophrenia social behavior frontal cortex Brodmann area 9