海马有髓神经纤维脱髓鞘在抑郁症中的作用

项目名称： 海马有髓神经纤维脱髓鞘在抑郁症中的作用

项目编号： No.81501156

项目类型： 青年科学基金项目

立项/批准年度： 2016

项目学科： 医药、卫生

项目作者： 黄春霞

作者单位： 重庆医科大学

项目金额： 17.5万元

中文摘要： 国内外对抑郁症的发病机制研究取得了很大进展，但仍有许多问题尚未阐明。我们近期发现抑郁症海马存在脱髓鞘改变。但是，抑郁症海马有髓神经纤维髓鞘及少突胶质细胞改变的客观、准确的三维定量研究，国内外未见报道。采用不同途径提高少突胶质细胞形成髓鞘的能力，保护髓鞘是否能够达到抗抑郁作用，更是不清楚。因此，我们提出假设：脱髓鞘改变可能是抑郁症的重要病理机制之一，通过肝x受体（LXRs）激动剂或抗Lingo-1抗体途径促进髓鞘形成可能起到抗抑郁作用。为验证此假设，我们将应用行为学方法、免疫荧光、电镜、体视学和分子生物学手段，研究抑郁症海马髓鞘、少突胶质细胞的改变以及修复髓鞘的干预措施对抑郁行为、抑郁症海马髓鞘和少突胶质细胞等的作用。研究结果将有助于进一步认识抑郁症的病理改变和分子机制，为寻找防治抑郁症的新手段提供新的靶点和切入点。

中文关键词： 抑郁症；海马；脱髓鞘；肝x受体；Lingo-1

英文摘要： The studies on the pathogenesis of depression have made great progress at home and abroad, but there are still many problems to be solved. Our recent research found the myelin injury in the hippocampus of depression. However, there has been no study investigating the changes of the oligodendrocytes and myelin sheaths of the hippocampus in depression with the new stereological methods. It is also unknown whether the protection of the myelin sheaths through improving the myelination capacity of oligodendrocytes with different ways has an antidepressant effect. Therefore, we propose the following hypothesis. Demyelination may be one of the important pathological mechanisms of depression, and LXRs agonists or anti-Lingo1 antibody treatments may play an antidepressant effect through preventing demyelination. To test the hypothesis, we will use behavioral methods, electron microscope technique, immunofluorescence technique, stereological methods and molecular biology techniques to investigate the oligodendrocyte and myelin sheath changes in the hippocampus of the depression model rats and the effects of the myelin sheath repairing strategies on these changes and the depression behaviors. The significance of this study is to further understand the pathological changes and molecular mechanisms of depression. Moreover, this study might also provide a new target and starting point for the future studies on the prevention and treatment of depression.

英文关键词： Depression;Hippocampus;Demyelination;LXRs;Lingo-1