Polysialylation in a DISC1 Mutant Mouse

• Published in: International journal of molecular sciences Vol. 23; no. 9; p. 5207
• Main Authors: Takahashi, Yuka, Abe, Chikara, Hane, Masaya, Wu, Di, Kitajima, Ken, Sato, Chihiro
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 06.05.2022; MDPI
• Subjects: Amygdala; Bipolar disorder; Brain; Cell adhesion; Cell adhesion molecules; DISC1; Disc1 protein; environmental factor; genetic factor; Mental disorders; Mutants; Mutation; NCAM; Neural cell adhesion molecule; Olfactory bulb; polysialic acid; Polysialylation; Prefrontal cortex; Rodents; Schizophrenia; Suprachiasmatic nucleus; tail suspension test; environmental factor; genetic factor; NCAM; acute stress; polysialic acid; mental disorder; schizophrenia; DISC1; polysialyltransferase
• ISSN: 1422-0067; 1661-6596; 1422-0067
• DOI: 10.3390/ijms23095207

Schizophrenia is a serious psychiatric disorder that affects the social life of patients. Psychiatric disorders are caused by a complex combination of genetic (G) and environmental (E) factors. Polysialylation represents a unique posttranslational modification of a protein, and such changes in neural cell adhesion molecules (NCAMs) have been reported in postmortem brains from patients with psychiatric disorders. To understand the G × E effect on polysialylated NCAM expression, in this study, we performed precise measurements of polySia and NCAM using a disrupted-in-schizophrenia 1 (DISC1)-mutant mouse (G), a mouse model of schizophrenia, under acute stress conditions (E). This is the first study to reveal a lower number and smaller length of polySia in the suprachiasmatic nucleus of DISC1 mutants relative to those in wild-type (WT) mice. In addition, an analysis of polySia and NCAM responses to acute stress in five brain regions (olfactory bulb, prefrontal cortex, suprachiasmatic nucleus, amygdala, and hippocampus) revealed that the pattern of changes in these responses in WT mice and DISC1 mutants differed by region. These differences could indicate the vulnerability of DISC1 mutants to stress.