Brain BDNF levels are dependent on cerebrovascular endothelium-derived nitric oxide.
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.
Unité INSERM U1093 Cognition, Action et Plasticité Sensorimotrice, University of Bourgogne Franche Comté, F-21000, Dijon, France.
Hayat
0000-0002-6503-3896
H
Banoujaafar
Unité INSERM U1093 Cognition, Action et Plasticité Sensorimotrice, University of Bourgogne Franche Comté, F-21000, Dijon, France.|Department of Rehabilitation, University Hospital, Dijon, France.
Alice
A
Monnier
Unité INSERM U1093 Cognition, Action et Plasticité Sensorimotrice, University of Bourgogne Franche Comté, F-21000, Dijon, France.
Nicolas
N
Pernet
Unité INSERM U1093 Cognition, Action et Plasticité Sensorimotrice, University of Bourgogne Franche Comté, F-21000, Dijon, France.
Aurore
A
Quirié
Unité INSERM U1093 Cognition, Action et Plasticité Sensorimotrice, University of Bourgogne Franche Comté, F-21000, Dijon, France.|IUT de Dijon, Département de Génie Biologique, Université de Bourgogne, Dijon, France.
Philippe
P
Garnier
Unité INSERM U1093 Cognition, Action et Plasticité Sensorimotrice, University of Bourgogne Franche Comté, F-21000, Dijon, France.
Anne
A
Prigent-Tessier
Unité INSERM U1093 Cognition, Action et Plasticité Sensorimotrice, University of Bourgogne Franche Comté, F-21000, Dijon, France.
Christine
C
Marie
D000818:Animals; D019208:Brain-Derived Neurotrophic Factor / Q000235:genetics / Q000378:metabolism*; D002540:Cerebral Cortex / Q000098:blood supply / Q000378:metabolism*; D002561:Cerebrovascular Disorders / Q000378:metabolism; D004730:Endothelium, Vascular / Q000378:metabolism*; D006624:Hippocampus / Q000098:blood supply / Q000378:metabolism*; D008297:Male; D009569:Nitric Oxide / Q000378:metabolism*; D052250:Nitric Oxide Synthase Type III / Q000378:metabolism; D010805:Physical Conditioning, Animal; D051381:Rats; D017208:Rats, Wistar; D020813:Receptor, trkB / Q000378:metabolism
D019208:Brain-Derived Neurotrophic Factor; D009569:Nitric Oxide; D052250:Nitric Oxide Synthase Type III; D020813:Receptor, trkB
TrkB; brain-derived neurotrophic factor; carotid arteries occlusion; nitric oxide; physical exercise