Ikeda Yuka, Nakashima Moeka, Yoshikawa Sayuri, Taniguchi Kurumi, Suga Naoko, Matsuda Satoru
Department of Food Science and Nutrition, Nara Women's University, Kita-Uoya Nishimachi, Nara 630-8506, Japan.
Biology (Basel). 2024 Dec 11;13(12):1039. doi: 10.3390/biology13121039.
Neuropsychiatric disorders are a public health concern, in which diagnosis and prognosis may be based on clinical symptoms that might often diverge across individuals. Schizophrenia is a major neuropsychiatric disorder, which may affect millions worldwide. However, the biochemical alterations of this disorder have not been comprehensively distinguished. In addition, there is less confidence in finding specific biomarkers for neuropsychiatric disorders, including schizophrenia, but rather a specific characteristic behavioral pattern. In general, maternal immune activation is considered to be one of the important factors in the development of neuropsychiatric disorders. Here, a mouse model of neuropsychiatric disorders was created, in which poly I:C, sodium dextran sulfate (DSS), and κ-carrageenan (CGN) were utilized for maternal immune activation during the pregnancies of mother mice. Subsequently, we examined the link between biochemical changes in p62 and/or glutamate aspartate transporter (GLAST) in the brains of offspring mice and the alteration in their experimental behavior scores. Furthermore, a therapeutic study was conducted on these neuropsychiatric disorder model mice using butyric acid, piceid, and metformin. It was found that some molecules could effectively improve the behavioral scores of neuropsychiatric model mice. Importantly, significant correlations between certain behavioral scores and p62 protein expression, as well as between the scores and GLAST expression, were recognized. This is the first report of a significant correlation between pathological behaviors and biochemical alterations in neuropsychiatric disorder model animals. This concept could contribute to the development of innovative treatments to at least ameliorate the symptoms of several psychiatric disorders.
神经精神疾病是一个公共卫生问题，其诊断和预后可能基于临床症状，而这些症状在个体之间往往存在差异。精神分裂症是一种主要的神经精神疾病，全球可能有数百万患者受其影响。然而，这种疾病的生化改变尚未得到全面区分。此外，对于找到包括精神分裂症在内的神经精神疾病的特定生物标志物，人们信心不足，而是更关注一种特定的特征性行为模式。一般来说，母体免疫激活被认为是神经精神疾病发展的重要因素之一。在此，创建了一种神经精神疾病小鼠模型，在母鼠怀孕期使用聚肌胞苷酸、硫酸葡聚糖钠（DSS）和κ-卡拉胶（CGN）进行母体免疫激活。随后，我们研究了子代小鼠大脑中p62和/或谷氨酸天冬氨酸转运体（GLAST）的生化变化与它们实验行为评分改变之间的联系。此外，使用丁酸、白藜芦醇和二甲双胍对这些神经精神疾病模型小鼠进行了治疗研究。结果发现，一些分子可以有效改善神经精神疾病模型小鼠的行为评分。重要的是，我们认识到某些行为评分与p62蛋白表达之间以及评分与GLAST表达之间存在显著相关性。这是首次报道神经精神疾病模型动物的病理行为与生化改变之间存在显著相关性。这一概念可能有助于开发创新疗法，至少改善几种精神疾病的症状。
