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令人信服的假说是“神经发育异常理论”，它认为大脑发育期间的微妙侮辱“是精神分裂症易感性的基础”。我们通过用神经发育阶段缺乏多不饱和脂肪酸(PUFA)的饮食喂养小鼠(PUFA(-)小鼠)来检验这一理论。PUFA(-)-小鼠的行为表型让人想起精神分裂症的早期阶段。有趣的是，髓鞘相关基因在PUFA(-)-小鼠的额叶皮质中下调，就像在精神分裂症死后大脑中一样。我们发现，上述下调是由于转录因子基因Tf-A和Tf-B表达减少所致。PUFA(-)-鼠脑组织中Tf-A和Tf-B的启动子区域DNA甲基化水平升高，可能是导致Tf-A和Tf-B表达降低的原因之一。

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.