抑郁症大鼠海马 BDNF 及其受体 TrkB 和p75NTR 的表达及米氮平的调节作用

摘要

目的：观察抑郁症模型大鼠学习记忆力改变情况，研究海马脑源性神经营养因子（ BDNF）、酪氨酸激酶受体B（ TrkB）和神经营养因子低亲和力受体（ p75NTR）蛋白的表达变化，以及米氮平的调节作用。方法制备抑郁症大鼠模型；采用Morris水迷宫实验方法记录大鼠游动距离变化；免疫组化染色方法测定海马BDNF、TrkB和7p5 NTR表达阳性区吸光度值。结果抑郁症模型大鼠在目标象限游动距离减少，海马BDNF及 TrkB 蛋白表达减少， p75NTR 蛋白表达增加；米氮平逆转上述行为学异常及蛋白表达异常（ p﹤0．01）。结论抑郁症模型大鼠可能存在BDNF-p75NTR通路信息传递增强，而抗抑郁治疗用药可能通过BDNF-TrkB信号通路的改变引起相应行为学改善。%Objectvi e This study is to evaluate the changes of learning and memory ability and the expression of brain-derived neurotrophic factor, trk receptor tyrosine kinase, and the p75 neurotrophin receptor in hippocampus of depressive rats, and to explore the underling regulation of mirtazapine .Methods Rat models were created by chronic unpredictable stress; Morris water maze test was used to record the swim lengths varity; Immunohistochemistry were conducted to assay the levels of BDNF, TrkB, and p75NTR proteins in the hippocampus .Results In the depression group, swim lengths in the target quadrant was decreased;the BDNF and TrkB protein levels were lower , whereas p75NTR protein level was higher.Mirtazapine treatment reversed the above abnormality.Conclusion Chronicunpredictable stress may harm learning and memory ability through BDNF-p75NTR pathway, whereas mirtazapine improves the impairment through BDNF-TrkB pathway.