Tez özetleri Astronomi ve Uzay Bilimleri Anabilim Dalı 2

The Effects of Atorvastatin on Neuropathologic Changes ın Diabetic Rats Induced by Stz
Diabetes is characterized by micro-vascular, macro-vascular complications, hyperglycemia. Oxidative stress, glucose, cholesterol metabolism and disorder of insulin signalization in central nervous system, formation of beta-amyloid plaques by hyperphosphorylation of tau proteins are the pathological conditions that occur in Alzheimer and diabetes. Although it is known that chronic inflammation, metabolically disorders and free radicals have role in diabetes their roles in learning and memory have not been elucidated.

Statins have neuroprotective effects in neurodegenerative diseases. The protective effect of atorvastatin in blood-brain barrier has been known. However, there is no study regarding its effects on Alzheimer and diabetic individuals. Our aim is to study the effects of atorvastatin on the neuropathological changes in STZ-induced diabetic rats.

In this study, experimental groups were organized in to 4 adult male rats: the diabetes induced rats with a single dose STZ administration (65 mg/kg) in the first day of the experiment and decapitated on the 25th day (I) and their controls (II); the diabetic rats that injected with atorvastatin (20mg/kg) on the last 10 days of the experiment and decapitated on the 25th day, (III) and their controls (IV). Nitrite-nitrate, interleukin-6, β-amyloid, glutathione peroxidase, neuron specific enolase and S100B protein levels were studied in blood, cerebral cortex and hippocampus homogenate. Additionally, beta-amyloid were examined histochemically and eNOS, iNOS, nNOS were examined immunohistochemically in hippocampus. In addition, the passive avoidance test to assess long term memory was performed in all groups.

Increased beta-amyloid formation in hippocampus of the diabetic rats decreased significantly with the atorvastatin treatment. S100B levels decreased after treatment with atorvastatin compared to diabetic group. We determined reduction in β-amyloid plaque formation and S100B levels, increasing in the expression of eNOS expression while decreasing iNOS after atorvastatin administered. Also we found that retention latency time in passive avoidance test decreased in diabetic rats and this period extended to by application of atorvastatin.

The results of our study showed us that atorvastatin had positive effects on long term memory and it could be an useful agent to treatment neurodegenerative disease which induced diabetes.