Selective effect of hypothyroidism on expression of myelin markers during development

Thyroid hormones are critical for maturation of the central nervous system. In a previous study, we showed a change in the pattern of mature myelinated nerve fibers by 2'3'-cyclic nucleotide 3'-phosphodiesterase (CNPase) in developing hypothyroid animals, which suggests a possible role for thyroid hormones in myelin compaction. The classical myelin markers myelin basic protein (MBP) and proteolipidic protein (PLP) are expressed later in oligodendroglial development, when myelin sheath formation is in progress. A myelin constituent designated myelin-associated/oligodendrocytic basic protein (MOBP) has been identified and related to myelin compaction. We assessed the developmental sequence of appearance of CNPase, MBP, MOPB, and PLP proteins in cerebellum (Cb) and corpus callosum (cc) in an experimental hypothyroidism model. The appearance of both MOBP isoforms occurred at postnatal day (P)25 and P30 in cc and Cb, respectively, followed by an increase with age in the control group. However, all the MOBP isoforms were weakly detectable in both regions at P30 from the hypothyroid (H) group, and the higher molecular weight isoform remains decreased in cc, even at P90. The developmental pattern of expression of CNPase, MBP, and PLP proteins was also delayed in the H group. CNPase and MBP expression was recovered in cc and Cb, whereas PLP remained below control levels at P90 in cc. Our data show that the experimental hypothyroidism affects the developmental pattern of the oligodendrocytic/myelin markers. Furthermore, thyroid hormone may modulate specific genes, as demonstrated by permanent down-regulation of MOBP and PLP expression in adulthood.     

MOBP基因在注意缺陷多动障碍大鼠前额叶皮层表达的研究

目的:探讨注意缺陷多动障碍(ADHD)动物模型SHR大鼠前额叶皮层MOBP基因表达情况,分析其在ADHD病理生理学中的意义.方法:应用RT-PCR、免疫组化、电镜技术检测该基因mRNA、蛋白表达情况以及轴突髓鞘形态变化.结果:RT-PCR结果显示SHR大鼠脑组织中MOBP mRNA表达水平(35.78±6.04)%明显低于正常对照WKY大鼠(69.41±7.43)%(P＜0.01);免疫组化结果提示SHR大鼠前额叶皮层髓鞘着色显著变浅、稀疏,着色面积占总面积比例(7.43±3.51)%较对照组WKY(14.39±5.82)%明显减少(P＜0.05);电镜观察结果显示,部分SHR大鼠髓鞘放射性结构呈直线性分布.结论:MOBP基因在SHR中的表达下调可能通过参与损害中枢神经系统髓鞘结构和功能,在ADHD病理机制中发挥作用.