Comprehensive understanding of pathobiology of mental illnesses by examining relationship between polyunsaturated fatty acids and oligodendrocyte precursor cells

精神分裂症病因学的一个有说服力的假说是“神经发育异常理论”，该理论认为大脑发育时期的细微损伤“是精神分裂症易感性的基础”。我们通过在神经发育阶段喂养缺乏多不饱和脂肪酸（PUFA）的小鼠（PUFA(-)-小鼠）来验证这一理论。PUFA（-）小鼠表现出早期精神分裂症的行为表型。有趣的是，在PUFA（-）小鼠的额叶皮层中，髓磷脂相关基因被下调，就像在精神分裂症患者死后的大脑中一样。我们发现上述下调是由转录因子基因TF-A和TF-B的表达减少引起的。来自PUFA(-)-小鼠大脑的TF-A和TF-B启动子区域显示DNA甲基化升高，这可能导致TF-A和TF-B表达降低。

One of the cogent hypotheses of schizophrenia etiology is"neurodevelopmental abnormality theory", which proposes that subtle insults during brain developmental period"underlies the susceptibility of schizophrenia. We tested this theory by raising mice with polyunsaturated fatty acid (PUFA)-deficient diet during neurodevelopmental stage (PUFA(-)-mice). The PUFA(-)-mice displayed behavioral phenotypes reminiscent of early stage of schizophrenia. Interestingly, myelin-related genes were down-regulated in the frontal cortex of PUFA(-)-mice as in the postmortem brains of schizophrenia. We revealed that the above downregulations are caused by decreased expressions of transcription factor genes, TF-A and TF-B. The promoter regions of TF-A and TF-B from the brains of PUFA(-)-mice showed elevated DNA methylation, which probably lead to the lowered expressions of TF-A and TF-B.