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

Year 2021, , 248 - 255, 30.12.2021

Birgül Altuğ İnci Turan , Hale Sayan Özaçmak , Veysel Haktan Özaçmak

https://doi.org/10.25048/tudod.976507

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

Supporting Institution

Zonguldak Bülent Ecevit Üniversitesi Bilimsel Araştırma Projeleri Koordinasyon Birimi

Project Number

2017-26259946-02

Thanks

Yok

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

Project Number

2017-26259946-02

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