Mechanisms of angiotensin II to induce depression in diabetes

The expression of angiotensin II (Ang II) has been reported in diabetes associated with hypertension and inflammatory processes. It has also been reported a link between Ang II, depression and diabetes; however, underlying mechanisms of Ang II-induced depression in this disease remain unclear. This review focuses on the possible mechanisms of Ang II to induce depression in diabetes. Ang II can induce pro-inflammatory events that activate indoleamine 2,3-dioxygenase and kynurenine monooxygenase. These activated enzymes act by decreasing the production of serotonin and increasing the production of quinolinic acid which acts on the N-methyl-d-aspartate receptor and the amino-methyl propionic acid receptor inducing decreased brain-derived neurotrophic factor (BDNF) expression and depression. Ang II can also induce the production of galectin 3 which has a depressant effect. Neuroinflammation induced by Ang II during diabetes can alter brain cells, event associated with functional disorders and depression. Furthermore, Ang II is capable of inducing oxidative stress in diabetes linked to depressive behaviors. In conclusion, Ang II has the potential to induce depression during diabetes through different mechanisms that involve inflammatory processes, oxidative stress, the production of galectin 3, and decrease in serotonin and BDNF. These findings open the possibility of using anti-Ang II drugs for the treatment of depressive behavior in diabetes.