Xanthine Oxidase Mediates Cerebrovascular Function Impairment in Chronically Stressed Mice

Chronic stress-induced depression is a major cerebrovascular risk factor, and the link between obesity and depression is strong. We have previously shown that chronic stress in obese rats significantly reduces cerebrovascular function, mediated by an increase in oxidative stress. Xanthine oxidase (XO) is a major source of oxidative stress, thus, we examined the effects of Febuxostat (XO inhibitor) on improving cerebrovascular function after the development of depressive like symptoms. Diet induced obesity (60 kcal% fat) started at 6 weeks of age in C57BL/6 mice (n=12) lasting for a total of twenty weeks. During the final eight weeks, 6 mice underwent the unpredictable chronic mild stress (UCMS; 5 days/week for 7 Hrs/day) model to elicit a depressive phenotype. On week twenty, the mice were euthanized and the middle cerebral arteries (MCA) were removed and positioned in a pressurize myobath. To test for vessel health, the MCA was exposed it to increasing concentrations of acetylcholine (Ach; 10−9M to 10−4M...