Deficiency of sterol regulatory element-binding protein-1c induces schizophrenia-like behavior in mice

Abstract

Schizophrenia is a hereditary disease that approximately 1% of the worldwide population develops. Many studies have investigated possible underlying genes related to schizophrenia. Recently, clinical studies suggested sterol regulatory element-binding protein (SREBP) as a susceptibility gene in patients with schizophrenia. SREBP controls cellular lipid homeostasis by three isoforms: SREBP-1a, SREBP-1c and SREBP-2. This study used SREBP-1c knockout (KO) mice to examine whether a deficiency in SREBP-1c would affect their emotional and psychiatric behaviors. Altered mRNA expression in genes downstream from SREBP-1c was confirmed in the brains of SREBP-1c KO mice. Schizophrenia-like behavior, including hyperactivity during the dark phase, depressive-like behavior, aggressive behavior and deficits in social interaction and prepulse inhibition, was observed in SREBP-1c KO mice. Furthermore, increased volume of the lateral ventricle was detected in SREBP-1c KO mice. The mRNA levels of several γ-aminobutyric acid (GABA)-receptor subtypes and/or glutamic acid decarboxylase 65/67 decreased in the hippocampus and medial prefrontal cortex of SREBP-1c KO mice. Thus, SREBP-1c deficiency may contribute to enlargement of the lateral ventricle and development of schizophrenia-like behaviors and be associated with altered GABAergic transmission.