Diabetes and depression : unveiling a potential biological link -

Abstract

Background: Depression and diabetes are prevalent diseases whose incidence rates are increasing worldwide. Epidemiological studies provide strong evidence that subjects with diabetes are at significantly higher risk of developing depression. Shared biological vulnerabilities may be involved in the comorbidity of depression and diabetes. However, the common functional and molecular mechanisms between the two disorders remain unknown. Reactive oxygen species (ROS) have been shown to be increased in both disorders. However, the sources and the mechanisms by which ROS lead to peripheral and central nervous system injury need to be elucidated. Aim: The aim of this study is to determine the role of NADPH-induced ROS in the onset of depression and diabetes. More importantly this project will evaluate the effect of depression, on the alteration of the NADPH oxidases pathway and its effect on the onset and development of diabetic complications, specifically neuropathy using functional, behavioral, structural, and molecular testing. Methods: A chronic stress procedure was used to induce depression in the control or non-obese type 2 diabetic mice. Sucrose test, tail suspension test, and forced swim test were performed to assess depression in mice. Raised beam walking test was used to assess behavioral malfunction in diabetic and depressed animals. RT-PCR allowed the measurement of mRNA levels of Nox1, PLP, and MBP. Western blots were used to assess the protein expression levels of Nox1 and myelin proteins. NADPH oxidase activity was used to measure the activation of the Nox enzymes and as a measurement of superoxide anion production. Results: Behavioral assessment of the animals shows a depressed like behavior in the diabetic animals resembling that of the experimentally induced depression in the control animals. Interestingly, the experimentally depressed diabetic mice showed an increase in the severity of depression. These observations were paralleled by an increase in the NADPH-dependent superoxide production conco