SELENBP1 overexpression in the prefrontal cortex underlies negative symptoms of schizophrenia.
Soojin KimSeong-Wook KimMai Anh Thi BuiYeji KimMinsoo KimJung-Cheol ParkNam-Heon KimGyeong Hee PyeonYong Sang JoJaewon JangHae-Young KohChae-Hong JeongMoonkyung KangHyo Jung KangYong-Woo LeeCraig A StockmeierJe Kyung SeongDong Ho WooJung-Soo HanYeon-Soo KimPublished in: Proceedings of the National Academy of Sciences of the United States of America (2022)
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.
Keyphrases
- bipolar disorder
- high fat diet induced
- prefrontal cortex
- functional connectivity
- cell proliferation
- wild type
- working memory
- spinal cord
- resting state
- end stage renal disease
- chronic kidney disease
- poor prognosis
- healthcare
- gene expression
- traumatic brain injury
- newly diagnosed
- mental health
- adipose tissue
- transcription factor
- blood brain barrier
- skeletal muscle
- long non coding rna
- depressive symptoms
- prognostic factors
- electronic health record
- cerebral ischemia
- sleep quality