The effect of exercise on purinergic receptor‐mediated cerebrovascular dysfunction in Alzheimer's disease

Abstract

IntroductionCerebrovascular dysfunction is a critical initial step of Alzheimer's disease (AD). Adenosine triphosphate (ATP) regulates cerebral blood flow through purinergic receptors. The aim of this study is to investigate the protective effect of exercise training on ATP‐induced purinergic receptor‐mediated cerebrovascular dysfunction in the AD and its underlying mechanisms.MethodsWe used the control mice (CON; C57BL/6), CON with exercise training (CON‐EX), AD mice (AD; APP/PS1) and AD with EX (AD‐EX). At 7 to 9 months of age, CON‐EX and AD‐EX mice underwent 10–12 weeks of aerobic exercise training, which consisted of 1 hour of treadmill running at 15m/min at a 5% grade. To test the purinergic receptor‐dependent vasoreactivity, a posterior cerebral artery (PCA) was isolated and ATP (2‐MeS‐ATP, 1 nmol/L to 10 μmol/L)‐induced dose‐dependent vascular dilation/constriction response was determined at 10–12 months of age. Western blotting was utilized to analyze the expression of P2Y2 receptors (P2Y2R), total eNOS (t‐eNOS) and phosphorylated eNOS (p‐eNOS) in the brain.ResultsATP induced vasodilation of PCA in CON and CON+EX mice, but it induced vasoconstriction in AD mice. Notably, exercise training reverses ATP‐induced vasoconstriction in the AD to vasodilation (AD+EX) comparable to CON mice. Western blotting data demonstrated that P2Y2R and p‐eNOS expression were significantly diminished in AD mice compared to CON mice, but they were elevated in AD‐EX mice brain. There was no significant difference in t‐eNOS expression among mice groups.ConclusionOur findings suggest that ATP‐induced purinergic receptor‐dependent cerebrovascular function is impaired in the AD. However, exercise training reverses ATP‐induced purinergic receptor‐dependent vasoconstriction to vasodilation mainly through the alteration of P2Y2R and p‐eNOS expression in the AD‐EX.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.