Deneysel alzheimer hastalığı modelinde voltaj bağımlı anyon kanalı-1 ve hiperfosforile tau inhibisyonunun araştırılması
Küçük Resim Yok
Tarih
2023
Yazarlar
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Dergi ISSN
Cilt Başlığı
Yayıncı
Düzce Üniversitesi
Erişim Hakkı
info:eu-repo/semantics/openAccess
Özet
Alzheimer Hastalığı (AH), idiyopatik (sebebi bilinmeyen) bir etiyolojiye sahip beynin primer bir nörodejeneratif hastalık olarak tanımlanmaktadır. Bu çalışmada, VDAC1'in pro-apoptotik aktivitesini önlemenin, AH'da hücre ölümünü inhibe etmek için ideal bir yöntem olabileceği düşünülmüştür. Çalışmada, AH modelinde gatekepeer olarakta bilinen voltaj bağımlı anyon kanalı proteininin inhibisyonunun ve davunetidin tedavisinin AH'nın primer patolojik belirteçleri üzerine ilişkisini ve hafıza - bellek eksikliklerini kurtarma yeteneklerini incelemek hedeflenmiştir. 2-3 aylık ve 230±30 gr ağırlığında 30 adet Wistar cinsi erkek sıçanlar tercih edildi. Her grupta 5 hayvan olacak şekilde rastgele KONTROL grubu, SHAM grubu, STZ grubu, STZ-DAV grubu, STZ-DIDS grubu ve STZ-DIDS-DAV grubu olmak üzere 6 gruba ayrıldı. AH modeli için intraserebroventriküler streptozotosin uygulandı. Deney süresince DIDS ve DAV ugulamaları intraperitonel yolla yapıldı. Davranış testlerinde radyal kol labirent (RKL) testi kullanıldı. Deney süresince 21 günlük uygulamadan sonra anestezi altındaki sıçanlardan kan ve beyin örnekleri alındı. Daha sonra ELIZA yöntemi ile biyokimyasal analizler yapıldı. SerumlardaTNF-?, caspase-3 ve MAPt değerleri bakımından gruplar arasında fark gözlenmezken, serum IL-10, TBARS, A?1-42, TSPO ve VDAC1 değerleri bakımından anlamlı fark saptandı. Gruplar arası beyin doku homejenatlarında IL-10 ve A?1-42 değerleri arası anlamlılık gözlenmezken, TNF-?, TBARS, caspase-3, MAPt, TSPO ve VDAC1 değerleri arasında anlamlı fark gözlemlendi. RKL testi verileri ön eğitim günleri ve eğitim günleri arasında farklılıklar saptandı. Deneysel AH modeli oluşturulan şıçanlarda, bu uygulamaların biyokimyasal ve davranış verileri üzerine hafıza - bellek eksikliklerini kurtarma yönünde etkili olabileceği daha fazla yapılacak çok yönlü çalışmalarla desteklenmelidir.
Alzheimer's Disease (AD) is defined as a primary neurodegenerative disease of the brain, which has an idiopathic etiology, causes characteristic neuropathological and neurochemical changes, has an insidious onset, lasts for years and progresses slowly. In this study, it was thought that inhibiting the pro-apoptotic activity of VDAC1 might be an ideal method to inhibit cell death in AD. The study, it was aimed to examine the relationship between the inhibition of voltage-dependent anion channel protein known as gatekepeer and davunetidine treatment on primary pathological markers of AD and their ability to recover memory-memory deficits in the AD model. A total of 30 male wistar rats weighing 230±30 g and 2-3 months were allocated. 5 animals in each group were randomly divided into 6 groups as CONTROL group, SHAM group, STZ group, STZ-DAV group, STZ-DIDS group and STZ-DIDS-DAV group. Intracerebroventricular streptozotocin was administered for the AH model. During the experiment, DIDS and DAV applications were performed intraperitoneally. The radial arm maze (RAM) test was used in behavioral tests. After 21 days of administration, blood and brain samples were taken from rats under anesthesia. Then, biochemical analyzes were performed by ELISA method. While no difference was observed between the groups in terms of TNF-?, caspase-3 and MAPt values in serum, a significant difference was found in serum IL-10, TBARS, A?1-42, TSPO and VDAC1 values. While no significant difference was observed between IL-10 and A?1-42 values in brain tissue homogenates between groups, a significant difference was observed between TNF-?, TBARS, caspase-3, MAPt, TSPO and VDAC1 values. Differences were found between the RAM test data and the pre-training days and the training days. The fact that these applications can be effective in recovering memory-memory deficits on biochemical and behavioral data in rats with experimental AD model should be supported by further multi-faceted studies. Experimental AD model in rats, it should be supported by further multidimensional studies that these applications can be effective in recovering memory - memory deficits on biochemical and behavioral data.
Alzheimer's Disease (AD) is defined as a primary neurodegenerative disease of the brain, which has an idiopathic etiology, causes characteristic neuropathological and neurochemical changes, has an insidious onset, lasts for years and progresses slowly. In this study, it was thought that inhibiting the pro-apoptotic activity of VDAC1 might be an ideal method to inhibit cell death in AD. The study, it was aimed to examine the relationship between the inhibition of voltage-dependent anion channel protein known as gatekepeer and davunetidine treatment on primary pathological markers of AD and their ability to recover memory-memory deficits in the AD model. A total of 30 male wistar rats weighing 230±30 g and 2-3 months were allocated. 5 animals in each group were randomly divided into 6 groups as CONTROL group, SHAM group, STZ group, STZ-DAV group, STZ-DIDS group and STZ-DIDS-DAV group. Intracerebroventricular streptozotocin was administered for the AH model. During the experiment, DIDS and DAV applications were performed intraperitoneally. The radial arm maze (RAM) test was used in behavioral tests. After 21 days of administration, blood and brain samples were taken from rats under anesthesia. Then, biochemical analyzes were performed by ELISA method. While no difference was observed between the groups in terms of TNF-?, caspase-3 and MAPt values in serum, a significant difference was found in serum IL-10, TBARS, A?1-42, TSPO and VDAC1 values. While no significant difference was observed between IL-10 and A?1-42 values in brain tissue homogenates between groups, a significant difference was observed between TNF-?, TBARS, caspase-3, MAPt, TSPO and VDAC1 values. Differences were found between the RAM test data and the pre-training days and the training days. The fact that these applications can be effective in recovering memory-memory deficits on biochemical and behavioral data in rats with experimental AD model should be supported by further multi-faceted studies. Experimental AD model in rats, it should be supported by further multidimensional studies that these applications can be effective in recovering memory - memory deficits on biochemical and behavioral data.
Açıklama
Anahtar Kelimeler
Fizyoloji, Physiology