Bioscience and Biotechnology Center, Nagoya University, Chikusa, Nagoya 464-8601, Japan.
Graduate School of Bioagricultural Sciences, Nagoya University, Chikusa, Nagoya 464-8601, Japan.
Int J Mol Sci. 2022 May 6;23(9):5207. 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.
精神分裂症是一种严重的精神疾病，会影响患者的社交生活。精神疾病是由遗传（G）和环境（E）因素复杂组合引起的。多聚唾液酸化是蛋白质的一种独特翻译后修饰，有报道称在精神疾病患者的尸检大脑中神经细胞黏附分子（NCAMs）存在这种变化。为了了解 G×E 对多聚唾液酸化 NCAM 表达的影响，在这项研究中，我们使用 DISC1 突变（G）小鼠，即精神分裂症的一种小鼠模型，在急性应激条件下（E），对多聚唾液酸和 NCAM 进行了精确测量。这是首次揭示相对于野生型（WT）小鼠，DISC1 突变体的视交叉上核中多聚唾液酸的数量更少、长度更短的研究。此外，对五个脑区（嗅球、前额叶皮层、视交叉上核、杏仁核和海马）的多聚唾液酸和 NCAM 对急性应激的反应进行分析表明，WT 小鼠和 DISC1 突变体的这些反应变化模式因脑区而异。这些差异可能表明 DISC1 突变体对压力的脆弱性。
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