Physical training restores brain-derived neurotrophic factor signaling in hypertensive rats

International audienceObjective: Hypertension is a major cause of cognitive decline even though the underlying mechanisms remain hypothetical. Supporting a contribution of deficient brain-derived neurotrophic factor (BDNF) signaling, animal studies recently reported low BDNF levels in the hippocampus of hypertensive rats as compared to their normotensive controls. Besides, physical training that is positively associated with cardiovascular health is also one of the most efficient strategies to increase brain BDNF levels and cognitive performance. These data led us to explore whether physical training may restore brain BDNF signaling in hypertensive rats and if right the mechanisms involved.Design and method: Experiments were performed on three groups of rats (n = 11 each). Sedentary spontaneously hypertensive rats (SHR), physically-trained SHR (SHR-T) and sedentary normotensive Wistar Kyoto rats (WKY). Physical training consisted in a daily (30-min) walking activity on a horizontal treadmill for 7 consecutive days. This protocol was previously shown to elevate hippocampal BDNF levels in normotensive rats. Systolic (SBP) and diastolic (DBP) blood pressures were measured by plethysmography. The hippocampus was collected 24 h after the last treadmill session in order to measure levels of BDNF, synaptophysin (SYN, as a marker of synaptogenesis), TrkB phosphorylated at tyrosine 816 (p-TrkB as a marker of TrkB activation by BDNF), eNOS phosphorylated at serine 1177 (as a marker of cerebrovascular eNOS activation by physical training) using Western blotting analysis.Results: SBP and DBP (mmHg) that were higher in SHR (180 +/- 8 and 150 +/- 12, respectively) than WKY (112 +/- 3 and 92 +/- 5, respectively) did not differ between SHR and SHR-T. By contrast, BDNF, SYN, p-TrkB and p-eNOS levels were significantly lower in SHR than WKY (p < 0.05), higher in SHR-T than SHR (p < 0.05) while no difference was observed between WKY and SHR-T. Of interest, a positive correlation was observed between BDNF and P-eNOS (r = 0,707, p < 0.001).Conclusions: Hypertension-induced deficient BDNF signaling in the hippocampus is fully restored by physical training through blood-pressure independent mechanisms. Further studies are needed to explore the role of cerebrovascular endothelium-derived NO in the control of brain BDNF signaling