Diabetes Incuced Cognitive Impairment is Associated with Increase of NLRP3 and Nitrotyrosine Levels in the Hippocampus of Rats

Abstract

Aim: Diabets mellitus is associated with impaired learning and memory. Neuroinflammation is a pathophysiological hallmark of diabetes which include production of cytokines. It was suggested that nitrative injury has been implicated in the pathophysiologic mechanism of diabetes. Nod-like receptor family pyrin domain-containing (NLRP) inflammasomes are important in the development of inflammatory response through production of IL-1β and IL-18. In the present study was aimed to examine the relationship between NLRP3, IL-1 β, nitrotyrosine levels and cognitive functions in diabetic rats.

Material and Methods: The rats were randomly divided into 2 groups: control and diabetic. Diabetes was induced by a single intraperitoneal injection of 60 mg/kg of streptozotocin (STZ). Body weight and blood glucose level were measured until euthanasia. Morris water maze (MWM)  was used to evaluate the cognitive function in rats. Hippocampal NLRP3, IL-1 β and nitrotyrosine levels were measured. 

Results: The results showed that the elevated  blood glucose was obseved in diabetic group. NLRP3 and nitrotyrosine levels were found to be increased in hippocampus of diabetic rats. There was no statsitical significance in the hippocampal IL-1β level with diabetes.  In the MWM, diabetic rats spent more time to find the submerged platform when compared with control rats,  implying a significant impairment of learning and memory, and this impairment was found to be statistically signifcant at day 5.  

Conclusion: Our results indicate that STZ induced diabetes causes learning and memory impairment in rats probably by generating nitrosative stress and increasing NLRP3 level in the hippocampus. 

Keywords

• Diabetes,Cognitive function,NLRP3,Nitrotyrosin

Diyabete Bağlı Kognitif Bozukluk Sıçanların Hipokampüslerinde NLRP3 ve Nitrotirozin Seviyelerinin Artışı ile İlişkilidir

Abstract

Amaç: Diyabetes mellitüs öğrenme ve hafıza bozukluğu ile birliktedir. Nöroinflamasyon sitokinlerin yapımını içeren diyabetin patofizyolojik bir işaretidir. Nitratif hasarın diyabetin patofizyolojik mekanizmasında yer aldığı ileri sürülmektedir. Nod-like receptor family pyrin domain-containing (NLRP), inflamazomlar IL-1β ve IL-18 yapımı ile inflamatuar cevabın gelişiminde önemlidir. Bu çalışmada diyabetik sıçanlarda NLRP3, IL-1 β, nitrotirozin düzeyleri ve kognitif fonksiyonlar arasındaki ilişkinin incelenmesi amaçlandı. 

Gereç ve Yöntemler: Sıçanlar rastgele 2 gruba ayrıldı: Kontrol ve diyabetik. Diyabet tek doz streptozotosin (STZ) uygulaması (60 mg/kg, intraperitoneal) ile oluşturuldu. Hayvanlar feda edilene kadar vücut ağırlıkları ve kan glukoz düzeyleri ölçüldü. Morris Su Labirenti (MWM) kognitif fonksiyonları değerlendirmek için kullanıldı. Hipokampal NLRP3, IL-1β ve nitrotirozin düzeyleri ELISA yöntemiyle belirlendi. 

Bulgular: Diyabetik grupta kan glukoz düzeylerinin yükseldiği gösterildi. NLRP3 ve nitrotirozin seviyelerinin diyabetik sıçanların hipokampüslerinde arttığı bulundu. Diyabet ile hipokampal IL-1β düzeylerinde istatistiksel olarak anlamlı değişiklik saptanmadı. MWM testinde diyabetik hayvanlar kontrollerle karşılaştırıldığında saklı platformu bulmak için daha fazla zaman harcadılar. Bu da öğrenme ve hafızanın anlamlı olarak bozulduğunu gösterdi ve bu bozukluk 5. günde istatistiksel olarak anlamlıydı. 

Sonuç: Sonuçlarımız STZ ile oluşturulan diyabetin muhtemelen hipokampüsde NLRP3 seviyesini artırarak ve nitrozatif stres oluşumu ile sıçanlarda öğrenme ve hafıza bozukluğuna neden olduğunu göstermektedir.

Keywords

• Diyabet,kognitif fonksiyon,NLRP3,nitrotirozin

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