Diabetes, depression, and peripheral neuropathy : the role of NADPH oxidases-induced reactive oxygen species in this vicious cycle

Abstract

Background: Diabetes Mellitus is a metabolic disease affecting over 347 million people worldwide. This disease comes with complications such as diabetic peripheral neuropathy (DPN) that affect 50percent of the patients. Its symptoms encompass sharp pains, and-or insensitivity to pain and temperature, demyelination, and impaired nerve conduction velocity. Depression is another complication of diabetes that occurs in some of the patients. The incidence of depression in the diabetic population is higher than that of the non-diabetic. Reactive oxygen species (ROS) have been shown to cause myelin damage in the central and peripheral nervous systems in depression and DPN respectively. The longer the coexistence of diabetes and depression, the more severe the myelin injury state. However, the mechanisms by which myelin injury is caused by these two disorders need to be elucidated. Aim: To assess the role of NADPH-induced ROS production in depression and diabetes-induced depressive-like behaviors in animal models. To examine whether depression can cause myelin alterations at the level of the peripheral nervous system. And to investigate whether the effect of comorbid diabetes and depression may further contribute to peripheral myelin alterations possibly exacerbating peripheral injury. Methods: A chronic 28-day stress protocol is employed to induce depressive-like behaviors in both control and non-obese type 2 diabetic mice. Tail suspension, forced swim, sociability and sucrose preference tests are performed to assess depression in mice. The raised beam walking test allows the assessment of sensorimotor malfunction in diabetic and depressed animals. mRNA levels of Nox1, Nox4, PLP, MBP and PMP22 will be assessed using Reverse transcription polymerase chain reaction (RT-PCR). Moreover, NADPH oxidase activity determines the activation of Nox enzymes measuring superoxide anion production. Results: Upon depression, altered molecular expressions of the aforementioned myelin proteins in both the central and peripheral