Journal
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
Volume 23, Issue 9, Pages -Publisher
MDPI
DOI: 10.3390/ijms23095207
Keywords
schizophrenia; polysialic acid; genetic factor; environmental factor; DISC1; NCAM; polysialyltransferase; tail suspension test; acute stress; mental disorder
Funding
- AMED [21gm6410007h0002, 22gm6410007h0002]
- Mizutani foundation [18-0316]
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Schizophrenia is a severe psychiatric disorder influenced by genetic and environmental factors. Changes in polysialylation of neural cell adhesion molecules have been found in the brains of patients with psychiatric disorders. This study investigates the effects of genetic (G) and environmental (E) factors on polysialylated NCAM expression using a schizophrenia mouse model and acute stress conditions. The study discovers differences in polysialylation and NCAM responses to stress in different brain regions, suggesting the vulnerability of the schizophrenia mouse model to stress.
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 x 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.
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