Luo Lu, Li Congqin, Du Xinxin, Shi Qilin, Huang Qiao, Xu Xiangyu, Wang Qiang
Department of Rehabilitation Medicine, Qingdao University, Qingdao, China.
Department of Rehabilitation Medicine, The Affiliated Hospital of Qingdao University, Qingdao, China.
Behav Brain Res. 2019 Apr 19;362:323-331. doi: 10.1016/j.bbr.2018.11.037. Epub 2018 Nov 27.
BDNF and proBDNF play an opposite role in hippocampal neurogenesis. What remains to be known is the effect of balance between BDNF and proBDNF in the ischemic hippocampus on pathogenesis of post-stroke depression (PSD) and the potential mechanisms of aerobic exercise (AE) on PSD. Wistar rats were randomly divided into control, Sham, Sedentary and AE groups. After PSD model was successful made, the blood lactate threshold corresponding speed (S) were measured. The behavioral tests (open field, forced swimming and sucrose preference tests) were performed before and after 4 weeks of aerobic treadmill training. HE staining and immunostaining for doublecortin (DCX) neurons were used to observe the changes of neuronal cell morphology and proliferation, migration of the neural progenitor cells (NPCs). The expression of mature brain-derived neurotrophic factor (BDNF), tropomyosin receptor kinase B (TrkB), precursor BDNF (proBDNF), pan-neurotrophin receptor 75 (p75NTR) proteins, BDNF mRNA in the ischemic hippocampus and serum adrenocorticotropic hormone (ACTH) and corticosterone (CORT) were detected by Western blotting, immunohistochemistry, RT-PCR and ELISA. Higher immobility time and levels of proBDNF, p75NTR, ACTH, CORT proteins and lower sucrose preference, total distance, climbing frequency and levels of BDNF, TrkB proteins, BDNF mRNA were observed in the Sedentary group. Neuronal cells in the ischemic hippocampus were loosely arranged and expression of DCX reduced in the Sedentary group. There were significant differences in above results between Sedentary and AE groups after 4 weeks of aerobic exercise. The balance between BDNF and proBDNF in the ischemic hippocampus are likely to play an important role in the pathogenesis of PSD. And AE could improve depression, hippocampal neurogenesis, and increase BDNF/proBDNF ratio in the ischemic hippocampus of the PSD rats.
脑源性神经营养因子（BDNF）和前体脑源性神经营养因子（proBDNF）在海马神经发生中发挥着相反的作用。尚不清楚缺血海马中BDNF和proBDNF之间的平衡对中风后抑郁症（PSD）发病机制的影响以及有氧运动（AE）对PSD的潜在作用机制。将Wistar大鼠随机分为对照组、假手术组、久坐组和有氧运动组。成功建立PSD模型后，测量血乳酸阈值对应的速度（S）。在有氧跑步机训练4周前后进行行为测试（旷场试验、强迫游泳试验和蔗糖偏好试验）。采用苏木精-伊红（HE）染色和双皮质素（DCX）神经元免疫染色观察神经元细胞形态变化以及神经祖细胞（NPCs）的增殖和迁移。通过蛋白质免疫印迹法、免疫组织化学、逆转录-聚合酶链反应（RT-PCR）和酶联免疫吸附测定（ELISA）检测缺血海马中成熟脑源性神经营养因子（BDNF）、酪氨酸激酶受体B（TrkB）、前体BDNF（proBDNF）、泛神经营养因子受体p75（p75NTR）蛋白、BDNF信使核糖核酸（mRNA）以及血清促肾上腺皮质激素（ACTH）和皮质酮（CORT）的表达。久坐组大鼠的不动时间延长，proBDNF、p75NTR、ACTH、CORT蛋白水平升高，蔗糖偏好、总距离、攀爬频率以及BDNF、TrkB蛋白、BDNF mRNA水平降低。久坐组缺血海马中的神经元细胞排列松散，DCX表达减少。有氧运动4周后，久坐组和有氧运动组在上述结果方面存在显著差异。缺血海马中BDNF和proBDNF之间的平衡可能在PSD发病机制中起重要作用。有氧运动可改善PSD大鼠的抑郁症状、促进海马神经发生，并增加缺血海马中BDNF/proBDNF比值。
