Effects of Experimental Diabetes on Cerebellar CREB/BDNF Pathway, Oxidative Stress and Motor Function

Abstract

Aim: Diabetes mellitus (DM) is a metabolic disorder with high mortality and morbidity rates. It is shown that DM causes neurobehavioral changes and locomotor disruption. Cyclic AMP Regulatory Element Binding Protein (CREB) and Brain-derived neurotrophic factor (BDNF) proteins plays a regulatuar role in numoreus functions in the brain such as memory, learning, and mood changes. The aim of this study was to investigate the effects of experimentally induced diabetes on cerebellum, how diabetes affects cerebellar motor function and to investigate the effect of diabetes on oxidative stress parameters and synaptic proteins. Material and Methods: In this study, a total of 24 male Wistar Albino rats (300-350 g) were divided into two groups as randomly, Control group and Diabetes mellitus group. Streptozotocin (STZ) was applied as a single 60 mg/kg dose (intraperitoneally) to perform DM. Fasting blood glucose was measured three days after STZ administration. Rats with a glucose level of >250 mg/kg were considered diabetic. The beam walking test was performed to evaluate motor function in rat. CREB/BDNF levels were assessed by ELISA method and oxidative stres parameters (Malondialdehyde (MDA) and glutathione (GSH) levels) were evaluated by biochemical method in uygucerebellum tissue. Results: In the beam walking test, the time to cross the platform was significantly longer in the diabetes group compared to the control group (p=0.001). The levels of BDNF in cerebellum were significantly lower in the diabetic group than in the control group (p=0.001). The levels of CREB and GSH in cerebellum were not different between the groups (respectively, p=0.99 p=0.394). The levels of MDA were higher in the diabetes group compared to the control group in the rat (p=0.001). Conclusion: This study showed that diabetes reduces the levels of BDNF in the cerebellum and increases distortion of motor functions by increasing oxidative stress.

Keywords

• Diabetes mellitus
• Cerebellum
• BDNF
• CREB
• Oxidative stress
• Motor coordination

Deneysel Diyabetin Serebellar CREB / BDNF Yolağı, Oksidatif Stres ve Motor Fonksiyona Etkisi

Abstract

Amaç: Diabetes mellitus (DM), mortalite ve morbidite oranı yüksek olan metabolik bir hastalıktır. DM’nin nörodavranışsal değişikliklere ve lökomotor aktivitede bozulmaya neden olduğu gösterilmiştir. Siklik AMP Regülatuar Eleman Bağlayıcı Protein (CREB) ve Beyin kaynaklı nörotrofik faktör (BDNF) proteinleri, beyindeki hafıza, öğrenme ve ruh hâli değişiklikleri gibi sayısız işlevde düzenleyici bir rol oynar. Bu çalışmanın amacı, deneysel olarak oluşturulan diyabetin serebellum üzerindeki etkilerini, diyabetin serebellar motor fonksiyonu nasıl etkilediğini ve diyabetin oksidatif stres parametreleri ve sinaptik proteinler üzerindeki etkisini araştırmaktır. Gereç ve Yöntemler: Bu çalışmada toplam 24 adet erkek Wistar Albino rat (300-350 gr) rastgele olarak Kontrol grubu ve Diabetes mellitus grubu olmak üzere iki gruba ayrıldı. DM oluşturmak için streptozotosin (STZ) 60 mg/kg tek doz (intraperitoneal) olarak uygulandı. Açlık kan şekeri, STZ uygulamasından üç gün sonra ölçüldü. Glikoz seviyesi >250 mg/kg olan sıçanlar diyabetik olarak kabul edildi. Sıçanlarda motor fonksiyonu değerlendirmek için kiriş yürüme testi yapıldı. Serebellum dokusunda CREB/BDNF düzeyleri ELISA yöntemi ile oksidatif stres parametreleri (Malondialdehit (MDA) ve glutatyon (GSH) düzeyleri) biyokimyasal yöntemle değerlendirildi. Bulgular: Kiriş yürüme testinde diyabetli grupta platformu geçme süresi kontrol grubuna göre anlamlı derecede daha uzundu (p=0,001). Serebellum BDNF seviyeleri diyabetik grupta kontrol grubuna göre anlamlı derecede düşük bulundu (p=0,001). Serebellumda CREB ve GSH düzeyleri gruplar arasında farklı değildi (sırasıyla, p=0,99 p=0,394). Sıçanlarda MDA düzeyleri diyabet grubunda kontrol grubuna göre daha yüksekti (p=0,001). Sonuç: Bu çalışma, diyabetin serebellumdaki BDNF düzeylerini azalttığını ve oksidatif stresi artırarak motor fonksiyonların bozulmasına neden olduğunu göstermiştir.

Keywords

• Diabetes mellitus
• Serebellum
• BDNF
• CREB
• Oksidatif stres
• Motor koordinasyon

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