Monnier Alice, Garnier Philippe, Quirie Aurore, Pernet Nicolas, Demougeot Céline, Marie Christine, Prigent-Tessier Anne
aINSERM U1093 Cognition, Action et Plasticité Sensorimotrice, University Bourgogne Franche-ComtébDepartment of Rehabilitation, CHRU DijoncDépartement Génie Biologique, IUT, DijondEA 4267 FDE, University Bourgogne Franche-Comté, Besançon, France.
J Hypertens. 2017 Feb;35(2):279-290. doi: 10.1097/HJH.0000000000001164.
Decreased brain-derived neurotrophic factor (BDNF) level has been reported in the hippocampus of hypertensive rats. The present study explored whether brain neurons and/or endothelial cells are targeted by hypertension with respect to BDNF expression and the potential of physical exercise to cope with hypertension.
Physical exercise was induced in spontaneously hypertensive rats (SHR) and Wistar Kyoto (WKY) rats. The hippocampus of sedentary and exercised rats (n = 6 for each group) were used for western blots to assess proBDNF, mature BDNF (mBDNF), tropomyosin-related kinase B (TrkB), P-TrkB (TrkB phosphorylated at tyrosine 816), synaptophysin, endothelial nitric oxide synthase (eNOS) and eNOS phosphorylated at serine 1177 protein levels. BDNF and proBDNF localization in the hippocampus was studied in WKY rats, SHR and exercised SHR (n = 5 each). mBDNF and proBDNF protein levels were also assessed in hippocampal slices prepared from SHR (n = 10) that were incubated for 24 h with the nitric oxide (NO) donor glyceryl trinitrate. SBP was measured by the tail-cuff method.
Exercise modified blood pressure neither in SHR nor WKY. As compared with WKY rats, SHR displayed decreased levels of mBDNF, P-TrkB, synaptophysin, eNOS and eNOS phosphorylated at serine 1177 but no change in proBDNF and TrkB levels. These effects coincided with low BDNF staining in both endothelial cells and neurons. Exercise improved the endothelium-derived NO system and the BDNF pathway in both strains. The NO donor increased mBDNF but decreased proBDNF levels.
Our results revealed that endothelial and neuronal BDNF expressions were both impaired in hypertension and that physical exercise improved hippocampal mBDNF levels and signaling through blood pressure-independent mechanisms.
有报道称高血压大鼠海马中脑源性神经营养因子（BDNF）水平降低。本研究探讨高血压是否针对脑神经元和/或内皮细胞影响BDNF表达，以及体育锻炼应对高血压的潜力。
对自发性高血压大鼠（SHR）和Wistar Kyoto（WKY）大鼠进行体育锻炼。将久坐不动和运动后的大鼠（每组n = 6）的海马用于蛋白质免疫印迹分析，以评估前体BDNF、成熟BDNF（mBDNF）、原肌球蛋白相关激酶B（TrkB）、磷酸化TrkB（酪氨酸816位点磷酸化的TrkB）、突触素、内皮型一氧化氮合酶（eNOS）以及丝氨酸1177位点磷酸化的eNOS的蛋白水平。在WKY大鼠、SHR和运动后的SHR（每组n = 5）中研究海马中BDNF和前体BDNF的定位。还对从SHR制备的海马切片（n = 10）进行mBDNF和前体BDNF蛋白水平评估，这些切片与一氧化氮（NO）供体甘油三硝酸酯孵育24小时。通过尾套法测量收缩压（SBP）。
运动对SHR和WKY大鼠的血压均无改变。与WKY大鼠相比，SHR的mBDNF、磷酸化TrkB、突触素、eNOS以及丝氨酸1177位点磷酸化的eNOS水平降低，但前体BDNF和TrkB水平无变化。这些影响与内皮细胞和神经元中低水平的BDNF染色一致。运动改善了两种品系的内皮源性NO系统和BDNF通路。NO供体增加了mBDNF水平，但降低了前体BDNF水平。
我们的结果表明，高血压会损害内皮细胞和神经元中的BDNF表达，而体育锻炼通过不依赖血压的机制提高了海马mBDNF水平并改善了信号传导。
