Histomorphometric and immunohistochemical evaluation of the frontal cerebral cortex in diabetic rats after treatment with melatonin

Abstract

ABSTRACT: The central nervous system is vulnerable to complications caused by diabetes. These complications lead to increased oxidative stress in the brain, resulting in damage to the cerebral cortex, among other regions. Insulin and hypoglycemic agents are still the most widely used treatments. However, current research with an experimental model of diabetes suggests the use of antioxidants, such as melatonin. Thus, we tested the hypothesis that exogenous melatonin may decrease or prevent the effects of diabetes in the frontal cortex of the rat brain. Fifty albino rats were allocated into five groups: GC = rats without diabetes induction, GD = diabetic rats induced by streptozotocin, GDM = streptozotocin-induced and melatonin-treated diabetic rats, GDI = diabetic rats induced by streptozotocin and treated with insulin, GDMI = diabetic rats induced by streptozotocin and treated with melatonin and insulin simultaneously. Diabetes was induced by intraperitoneal administration of streptozotocin (60mg/kg). Insulin (5U/day) was administered subcutaneously and melatonin (10mg/kg) by drinking water; both treatments last days after. We analyzed animals’ weight, the cytokines IL-6 and TNF-α, apoptosis, glycogen, and did morphometry and histopathology of the frontal cortex were analyzed. The results showed that the cerebral cortex of the diabetic animals presented axonal degeneration, reduced number of neurons in the cortex, reduced glycogen, increased IL-6 and TNF-α expression, high apoptotic index, and reduced animal weight and the brain. Treatment with melatonin associated or not with insulin prevented such effects. Thus, we conclude that melatonin associated with insulin may be an alternative for avoiding the impact of diabetes in the brain’s frontal cortex.