Banoujaafar Hayat, Monnier Alice, Pernet Nicolas, Quirié Aurore, Garnier Philippe, Prigent-Tessier Anne, Marie Christine
Unité INSERM U1093 Cognition, Action et Plasticité Sensorimotrice, University of Bourgogne Franche Comté, F-21000, Dijon, France.
Department of Rehabilitation, University Hospital, Dijon, France.
Eur J Neurosci. 2016 Sep;44(5):2226-35. doi: 10.1111/ejn.13301. Epub 2016 Jul 14.
Scientific evidence continues to demonstrate a link between endothelial function and cognition. Besides, several studies have identified a complex interplay between nitric oxide (NO) and brain-derived neurotrophic factor (BDNF), a neurotrophin largely involved in cognition. Therefore, this study investigated the link between cerebral endothelium-derived NO and BDNF signaling. For this purpose, levels of BDNF and the phosphorylated form of endothelial NO synthase at serine 1177 (p-eNOS) were simultaneously measured in the cortex and hippocampus of rats subjected to either bilateral common carotid occlusion (n = 6), physical exercise (n = 6) or a combination of both (n = 6) as experimental approaches to modulate flow-induced NO production by the cerebrovasculature. Tropomyosin-related kinase type B (TrkB) receptors and its phosphorylated form at tyrosine 816 (p-TrkB) were also measured. Moreover, we investigated BDNF synthesis in brain slices exposed to the NO donor glyceryl trinitrate. Our results showed increased p-eNOS and BDNF levels after exercise and decreased levels after vascular occlusion as compared to corresponding controls, with a positive correlation between changes in p-eNOS and BDNF (r = 0.679). Exercise after vascular occlusion did not change levels of these proteins. Gyceryl trinitrate increased proBDNF and BDNF levels in brain slices, thus suggesting a possible causal relationship between NO and BDNF. Moreover, vascular occlusion, like exercise, resulted in increased TrkB and p-TrkB levels, whereas no change was observed with the combination of both. These results suggest that brain BDNF signaling may be dependent on cerebral endothelium-derived NO production.
科学证据不断证明内皮功能与认知之间存在联系。此外，多项研究已确定一氧化氮（NO）与脑源性神经营养因子（BDNF）之间存在复杂的相互作用，BDNF是一种在认知中起重要作用的神经营养因子。因此，本研究调查了脑内皮源性NO与BDNF信号传导之间的联系。为此，在接受双侧颈总动脉闭塞（n = 6）、体育锻炼（n = 6）或两者结合（n = 6）的大鼠的皮质和海马中，同时测量BDNF水平和内皮型一氧化氮合酶丝氨酸1177位点的磷酸化形式（p-eNOS），这些作为调节脑血管流量诱导的NO产生的实验方法。还测量了B型原肌球蛋白相关激酶（TrkB）受体及其酪氨酸816位点的磷酸化形式（p-TrkB）。此外，我们研究了暴露于NO供体硝酸甘油的脑片中BDNF的合成。我们的结果显示，与相应对照组相比，运动后p-eNOS和BDNF水平升高，血管闭塞后水平降低，p-eNOS和BDNF的变化之间呈正相关（r = 0.679）。血管闭塞后运动并未改变这些蛋白质的水平。硝酸甘油增加了脑片中proBDNF和BDNF的水平，因此表明NO与BDNF之间可能存在因果关系。此外，与运动一样，血管闭塞导致TrkB和p-TrkB水平升高，而两者结合未观察到变化。这些结果表明，脑BDNF信号传导可能依赖于脑内皮源性NO的产生。
