海马有髓神经纤维脱髓鞘在抑郁症中的作用

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.

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。

国内外对抑郁症的发病机制研究取得了很大的进展。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。采用不同途径提高少突胶质细胞形成髓鞘的能力，保护髓鞘是否能达到抗抑郁作用，目前仍不清楚。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，通过抗Lingo-1抗体或肝x受体（LXRS）激动剂途径促进髓鞘形成可能起到抗抑郁作用，另外跑步锻炼和抗抑郁药物氟西汀治疗可能通过影响海马有髓神经纤维髓鞘和少突胶质细胞发挥抗抑郁作用。因此，我们应用行为学方法、免疫荧光、电镜、体视学和分子生物学手段，研究了抑郁症海马髓鞘、少突胶质细胞的改变，恢复髓鞘的干预措施，跑步锻炼以及氟西汀对抑郁行为、抑郁症海马髓鞘和少突胶质细胞的作用。我们主要的研究发现是：慢性不可预见性应激（CUS）抑郁症模型大鼠海马结构内存在有髓神经纤维脱髓鞘改变；抑郁模型大鼠海马CA1区、CA3区、DG区内少突胶质细胞数量下降，氟西汀治疗可以防止海马内CA1区、CA3区的CNPase+少突胶质细胞的丢失；抑郁模型大鼠海马CA3和DG区内的Olig2+胶质细胞数量，以及CA1区，CA3区和DG区内的NG2+胶质细胞数量均存在显著性减少，跑步锻炼对抑郁模型大鼠大脑海马DG区内少突胶质前体细胞的增殖分化具有明显保护作用；抗Lingo-1抗体可以改善抑郁症大鼠的认知障碍，抗Lingo-1抗体增加抑郁症伴认知障碍大鼠海马CA3区，DG区少突胶质细胞数量。这些研究结果为研究髓鞘和少突胶质细胞改变参与抑郁症发病机制及抗抑郁治疗机制的可能性提供了有力的科学依据。