经鼻腔移植骨髓间充质干细胞通过内源性神经再生等途径改善小鼠抑郁行为的机制研究

Depression is a common psychiatric disorder with a complex and multifactor aetiolog. The World Health Organization (WHO) report has predicted that major depression will become a key cause of illness-induced disability by the year 2020, second only to ischemic heart diseases. But the exact pathophysiology has not been fully identified. One of key points of depression is the damage of nerve regeneration in the hippocampus. Bone marrow mesenchymal stem cells have the advantages of multi-directional differentiation potential, rich source, can promote the nerve regeneration and inhibit inflammation, but whether BMSCs is suitable for depression still remain unclear. Our preliminary data confirmed that BMSCs after intranasal transplantation could improve depressive-like behavior after cerebral hemorrhage in mice. In this proposal, we hypothes that BMSCs could improve depressive behavior in mice through a comprehensive mechanism. We will apply the classic chronic unpredictable stress model of depression in mice, intranasal delivery, fluoxetine as positive control..We will determine the location、migration and differentiation of SPOI labled BMSCs in brain after intranasal deliver by using MRI. A series of behavioral assessments will be used to detect the improvement of behavior in mice, molecular biological techniques will be applied to detect the expression of inflammation, nerve regeneration and HPA axis related factors. The present project will help to provide a new theoretical evidence for stem cell treatment of depression.

抑郁症是一组多重原因所致的情感障碍疾病，到2020年抑郁症将成为困扰人类健康的最重要疾病，病理生理机制迄今未明。抑郁症发病的核心之一是海马神经再生受损。骨髓间充质干细胞具有多向分化潜能、来源丰富等优点，可以通过促进内源性神经再生、抑制炎症反应等多种机制发挥作用，但其对于抑郁症的作用尚无阐述。我们的前期试验证实，经鼻腔移植BMSCs可改善小鼠脑出血后抑郁样行为。因此我们提出假设，经鼻腔移植BMSCs可通过综合作用机制改善小鼠抑郁行为。本课题拟应用小鼠慢性不可预见性应激抑郁模型，经鼻腔移植BMSCs，以氟西汀为阳性对照药，核磁下活体动态示踪移植SPOI标记的BMSCs的存活、分化，多种行为学检测小鼠抑郁行为的改善，并通过免疫染色病理分析内源性神经再生、海马体积，分子生物学技术检测抑郁小鼠脑内炎症反应、神经再生、HPA轴相关因子表达等，期待为干细胞治疗抑郁症提供新的立论依据。

抑郁症是一组多重原因所致的情感障碍疾病，到2020年抑郁症将成为困扰人类健康的最重要疾病，病理生理机制迄今未明。抑郁症发病的核心之一是海马神经再生受损。骨髓间充质干细胞具有多向分化潜能、来源丰富等优点，可以通过促进内源性神经再生、抑制炎症反应等多种机制发挥作用，但其对于抑郁症的作用尚无阐述。我们的前期试验证实，经鼻腔移植BMSCs可改善小鼠脑出血后抑郁样行为。因此我们提出假设，经鼻腔移植BMSCs可通过综合作用机制改善小鼠抑郁行为。本课题应用小鼠慢性不可预见性应激抑郁模型，经鼻腔移植BMSCs，多种行为学检测小鼠抑郁行为均获得改善，并通过免疫染色病理分析内源性神经再生在改善抑郁小鼠抑郁样行为中发挥重要作用，期待为干细胞治疗抑郁症提供新的立论依据。