跑步锻炼修复抑郁症海马髓鞘的机制研究

大量研究表明跑步锻炼对抑郁症有治疗作用，但其治疗机制仍不清楚。脑内的髓鞘改变在抑郁症中具有重要地位，海马是抑郁症受累的关键脑区。我们前期的体视学研究发现抑郁模型动物海马内髓鞘显著减少，预实验结果提示跑步锻炼则可能通过影响少突胶质细胞的分化、成熟及髓鞘成分合成以修复抑郁症海马髓鞘。但目前跑步锻炼修复抑郁症海马髓鞘的分子机制并不清楚。因此，本课题拟结合多种行为学测试方法，采用脑立体定位注射、腺相关病毒载体基因沉默、细胞培养、体视学、透射电镜、免疫荧光、分子生物学等技术，探讨跑步锻炼是否通过激活抑郁症海马少突胶质细胞上NRG1/ErbB2通路，促进少突胶质前体细胞的分化、成熟；是否通过激活抑郁症海马内成熟少突胶质细胞内PGC-1α/PPARγ通路，促进髓鞘成分合成，最终促进髓鞘再生，修复髓鞘。本课题的研究将有助于进一步认识跑步锻炼的抗抑郁机制，对将来寻找防治抑郁症的新靶点具有重要意义。

Large number of studies have shown that running exercise has a therapeutic effect on depression, but the therapeutic mechanism is still unclear. Changes of the myelin sheaths in the brain play an important role in depression, and the hippocampus is the key brain region involved in depression. Our previous stereological studies found that the myelin sheaths in the hippocampus significantly decreased in the model animals of depression, while our preliminary study indicated that running exercise might repair the hippocampal myelin sheaths in depression through affecting the differentiation and maturation of oligodendrocyte and the synthesis of myelin components. The molecular mechanism for the fact that running exercise repairs the myelin sheaths of hippocampus in depression is not well understood. Therefore, in this project, we will study whether running exercise promotes the differentiation and maturation of oligodendrocyte precursor cells through activating NRG1/ErbB2 pathway in hippocampal oligodendrocytes of depression. In addition, we will study whether running exercise promotes the synthesis of myelin components though activating the PGC-1α/PPAR pathway in the mature oligodendrocytes in hippocampus of depression, and ultimately enhances myelin regeneration and repairs myelin sheaths. In the study, a variety of behavioral test methods, brain stereotactic injection, adenovirus vector gene silencing, cell culture, stereology, transmission electron microscopy, immunofluorescence and molecular biology techniques will be used. This study will help to explain the antidepressant mechanism of running exercise, and it is of great significance to find a potential target for the prevention and treatment of depression in the future.