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Brain BDNF levels are dependent on cerebrovascular endothelium-derived nitric oxide

Abstract : 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.
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Contributeur : CAPS - université de Bourgogne Connectez-vous pour contacter le contributeur
Soumis le : mardi 25 octobre 2016 - 11:06:02
Dernière modification le : jeudi 23 juillet 2020 - 11:04:02

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Hayat Banoujaafar, Alice Monnier, Nicolas Pernet, Aurore Quirie, Philippe Garnier, et al.. Brain BDNF levels are dependent on cerebrovascular endothelium-derived nitric oxide. European Journal of Neuroscience, 2016, 44 (5), pp.2226 - 2235. ⟨10.1111/ejn.13301⟩. ⟨hal-01387127⟩



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