Hypertension depresses but exercise training restores both Mfsd2a expression and blood-brain barrier function within PVN capillaries

Abstract

Hypertension augments while exercise training corrects the increased vesicle trafficking (transcytosis) across the blood-brain barrier (BBB) within preautonomic areas and the autonomic imbalance. There is no information on possible mechanism(s) conditioning these effects. Knowing that Mfsd2a is the major transporter of docosahexaenoic acid (DHA) and that Mfsd2a knockout mice exhibited leaky BBB, we sought to identify its possible involvement in hypertension- and exercise-induced transcytosis across the BBB. SHR and Wistar rats were submitted to treadmill training (T) or kept sedentary (S) for 4 weeks. Resting hemodynamic/autonomic parameters were recorded in conscious chronically cannulated rats. BBB permeability within the hypothalamic paraventricular nucleus (PVN) was evaluated in anesthetized rats. Brains were harvested for Mfsd2a and caveolin-1 (an essential protein for vesicle formation) expression. SHR-S vs. Wistar-S exhibited elevated arterial pressure (AP) and heart rate (HR), increased vasomotor sympathetic activity, reduced cardiac parasympathetic activity, greater pressure variability, reduced HR variability and depressed baroreflex control. SHR-S also showed increased BBB permeability, reduced Mfsd2a and increased caveolin-1 expression. SHR-T vs. SHR-S exhibited increased Mfsd2a density, reduced caveolin-1 protein expression, normalized PVN BBB permeability, which were accompanied by resting bradycardia, partial AP drop, reduced sympathetic and normalized cardiac parasympathetic activity, increased HR variability and reduced pressure variability. No changes were observed in Wistar-T vs. Wistar-S. Training is an efficient tool to rescue Mfsd2a expression, which by transporting DHA into the endothelial cell reduces caveolin-1 availability and vesicles' formation. Exercise-induced Mfsd2a normalization is an important mechanism to correct both BBB function and autonomic control in hypertensive subjects.

Interleukin 17A Contributes to Blood‐Brain Barrier Disruption of Hypothalamic Paraventricular Nucleus in Rats With Myocardial Infarction

“…The permeability of the BBB in the PVN and cortex regions was assessed through the quantification of extravasation of the low‐molecular‐weight dye FITC10, following the method outlined in prior studies. 12 , 26 , 27 , 28 In brief, 2 binary images were generated from the fluorescent images using ImageJ software (National Institutes of Health, Bethesda, MD). The first binary image contained only FITC10 signal (representing both intravascular and extravascular FITC10), whereas the second binary image contained colocalized FITC10 and RHO70 signals (indicating intravascular FITC10 exclusively).…”