Effect of melatonin and vitamin E on the expression of n-cam proteins in hippocampus and cortex in brain of experimentally induced diabetic rats

ABSTRACT PhD Thesis EFFECT OF MELATONIN AND VITAMIN E ON THE EXPRESSION OF NCAM PROTEINS IN HIPPOCAMPUS AND CORTEX IN BRAIN OF EXPERIMENTALLY INDUCED DIABETIC RATS Mehmet TUZCU Firat University Graduate School of Natural and Applied Sciences Department of Biology 2004, Page: 62 Hyperglycemia plays a critical role in the development and progression of diabetic neuropathy. One of the mechanisms by which hyperglycemia causes neural degeneration is via the increased oxidative stress that accompanies diabetes. Neural cell adhesion molecules (NCAMs) are members of the immunoglobulin superfamily. There are three major NCAM forms referred to as NCAM 180, NCAM 140, and NCAM 120 which are generated by alternative splicing. It has been proposed that NCAMs mediate the synaptic changes that occur during learning and memory formation. The present study was designed to evaluate the expression of neural cell adhesion molecules (NCAM) and to examine effect of melatonin and vitamin E on this expression. Diabetes was induced in rats via intraperitoneal streptozotocin injection. NCAM expression was detected in the hippocampus, cortex by an western blotting method. In diabetes, especially uncontrolled diabetes increase in the oxidative activity, insufficiency of antioxidant defence and protein glycosylation negatively effect the glucose metabolism. Malondialdehyde (MDA) which is the product of lipid peroxidation increases in diabetes. MDA can make reactions with amino groups of nucleic acids, proteins and phospholipids. Glutathione (GSH) prevents cells from oxidant damage by making reactions with free radicals and peroxides. Furthermore, it prevent most proteins from being inactive by holding sulphydryl groups reduced, in proteins structure. In experimental diabetic studies, excessive decrease was found in GSH levels. In diabetes, MDA was found to be increased, meanwhile GSH decreased. In the present study, the changes in NCAM expression pattern. MDA concentrations and GSH levels were investigated in hippocampus and cortex of STZ-induced diabetic rats, the effects of two potent antioxidant (melatonin and vitamin E) were also studied. For this aim, MDA and GSH contents were measured in control, STZ-induced diabetic rats and antioxidant (such as melatonin and vitamin E) treated rats in hippocampus and cortex. Significance of differences between groups was evaluated by means of two-way analysis of variance in conjunction with Bonferroni's t- statistics, and/7-values <0.05 were considered statistically significant. The results suggest that streptozotocin- induced diabetes causes an imbalance in expression of NCAM in those brain regions involved in learning and memory. In addition, it was found that the MDA level decreased and GSH level increased in diabetic groups suplied with melatonin and vitamin E when compared to diabetic groups. Key words: Diabet, STZ, Free radicals, NCAM, Hippocampus, Cortex, Lipid peroxidation, Glutathione, Melatonin. Vitamin E, Western blotting. VII