Effects of agmatine in streptozotocine induced experimental alzheimer model

Yıl 2013, Cilt: 3 Sayı: 3, 145 - 153, 30.01.2014

Müge Şirvancı Yalabık Özer Şehirli Tijen Utkan Feyza Arıcıoğlu

Öz

Objectives: Alzheimer’s disease is a neurodegenerative disorder characterized by progressive loss of memory followed by complete dementia. Furthermore it is the commonest form of dementia affecting older people. In this study we investigated the role of agmatine (Agm) on learning and memory and on parameters of oxidative stress in intracerebroventricular (i.c.v) streptozotocin (STZ) model of Alzheimer’s disease in rats. 

Materials and Methods: We grouped rats as: naive control, sham operated, STZ and STZ+agmatine. Rats were injected bilaterally i.c.v STZ (3mg/kg) using stereotaxic frame on day 1 and 3 to induce experimental Alzheimer’s disease. After 14 days from 1st STZ injection, learning and memory impairment of rats were observed in passive avoidance. Following this test, agmatine administered intraperitoneal (i.p.) 40mg/kg twice daily for 7 days. These animals were again subjected to these behavioral tests after 7 days agmatine treatment. On the 21st day after 1st STZ injection all groups were sacrificed by decapitation and brain tissues were collected for oxidative stress measurement. Malondialdehyde (MDA), glutathione (GSH) levels and myeloperoxidase (MPO) activity were measured for estimation of oxidative stress.

Results: In this study it has been demonstrated that i.c.v STZ in Alzheimer model can cause disorder in cognitive functions and oxidative damage. Agmatine treatment is found to be effective to prevent both cognitive deficits as well as the oxidative damage. 

Conclusion: According to results of the current study agmatine, as an endogenous molecule, might be an important modulator in alzheimer’s etiopathogenesis.

Key words: Agmatine, Alzheimer’s disease, intracerebroventricular streptozotocin, oxidative damage, learning and memory

Anahtar Kelimeler

Agmatine, Alzheimer’s disease, intracerebroventricular streptozotocin, oxidative damage, learning and memory

Streptozotosin ile oluşturulan deneysel alzheimer modelinde agmatinin etkilerinin araştırılması

Öz

Amaç: Alzheimer geri dönüşümsüz ve ilerleyici hafıza kaybını takiben tam demansla karakterize nörodejenaratif bir bozukluktur. Yaşlanmayla insanlarda en sık görülen demans formudur. Bu çalışmada sıçanlarda intraserebroventriküler (i.c.v) streptozotosin (STZ) ile oluşturulmuş Alzheimer modelinde agmatinin (Agm) öğrenme ve bellek fonksiyonlarına etkisi ve bu etkinin oksidatif hasar açısından mekanizması araştırılmıştır. 

Gereç ve Yöntem: Çalışmamızda Sprague-Dawley erkek sıçanlar kullanılmış, kontrol, sham opere, STZ ve STZ+Agm olmak üzere 4 gruba ayrılmışlardır. Alzheimer modeli oluşturmak için stereotaksik yöntem ile sıçanlara i.c.v olarak bilateral STZ 3 mg/kg dozda 48 saat arayla 2 defa uygulanmış ve ilk uygulamayı takiben 14 gün beklenmiştir. On beşinci günde pasif sakınma tesi ile öğrenme ve bellek fonksiyonları değerlendirilmiştir. Öğrenmesinin bozulduğu gösterilen sıçanlara 7 gün boyunca günde 2 defa 40mg/kg dozda Agm intraperitoneal (i.p.) olarak uygulanmış ve takiben aynı testler tekrarlanmıştır. Tüm gruplar davranış testleri bittikten sonra (21. günde) dekapite edilerek beyin dokuları toplanmış ve oksidatif hasarı değerlendirmek için malondialdehit (MDA), glutatyon (GSH) seviyeleri ve myeloperoksidaz (MPO) aktivitesi ölçümleri yapılmıştır.

Bulgular: İntraserebroventriküler STZ ile oluşturulmuş alzheimer modelinde kognitif fonksiyonlarında belirgin bozulma olduğu ve bu bozulmaya oksidatif hasarın eşlik ettiği gösterilmiştir. Agmatin tedavisi ile hem kognitif fonksiyon hem de oksidatif hasarı önlemiştir. 

Sonuç: Bu bulgulara dayanarak endojen bir madde olan agmatinin alheimer etyopatogenezinde önemli bir düzenleyici olabileceği düşünülmüştür.

Anahtar Kelimeler : Agmatin, Alzheimer, intraserebroventiküler streptozotosin, oksidatif hasar, öğrenme ve bellek

Anahtar Kelimeler

Agmatin, Alzheimer, intraserebroventiküler streptozotosin, oksidatif hasar, öğrenme ve bellek

Kaynakça

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