Publication: Deneysel alzheimer modelinde tosilizumab’ın etkilerinin araştırılması
Abstract
1. ÖZET DENEYSEL ALZHEİMER MODELİNDE TOSİLİZUMAB’IN ETKİLERİNİN ARAŞTIRILMASI Öğrencinin Adı: Ersin Aslan Danışmanı: Doç. Dr. H. Kübra Elçioğlu Marmara Üniversitesi Eczacılık Fakültesi Farmakoloji Amaç: Alzheimer Hastalığı’nda (AH) nöroinflamasyon önemli rol oynamaktadır. Hastalığın patojenezinde artan interlökin (IL)-6’nın pleiotropik aktivite gösteren bir proinflamatuvar olduğu bildirilmiştir. Monoklonal IL-6 reseptör antikoru olan Tosilizumab (TCZ) IL-6 sinyal iletimini inhibe etmektedir. Çalışmamızda streptozotosin (STZ)’nin intraserebroventriküler (i.c.v.) uygulamasıyla oluşturulan Alzheimer modelinde kognitif bozukluklarda Tosilizumab’ın etkilerinin araştırılması amaçlanmıştır. Gereç ve Yöntem: Çalışmada Sprague-Dawley suşu erkek sıçanlar; STZ, kontrol ve STZ+TCZ olmak üzere 3 gruba ayrılmışlardır. Alzheimer modeli oluşturabilmek için, STZ+TCZ ve STZ grubu sıçanlara (3 mg/ kg) bilateral STZ i.c.v olarak uygulanmıştır. Tosilizumab 21 gün boyunca tek doz olmak üzere STZ’nin ilk dozundan 1 saat önce i.c.v. olarak kullanılmıştır. Öğrenme ve bellek bozukluğu 15-21. günler arasında değerlendirilmiş ve 21. gün histopatolojik değişimleri incelemek için sıçanlar dekapite edilmiştir. Histopatolojik değişimler hematoksilen-eozin kullanılarak incelenmiştir. Bulgular: Streptozotosin enjeksiyonu pasif sakınma testinde karanlık bölmeye geçiş süresinde anlamlı bir düşüşe, Morris havuz labirenti testi performansında da anlamlı bir azalmaya neden olmuştur. Tosilizumab uygulanan sıçanlar STZ ile karşılaştırıldığında beyin kesitlerinde; nöronlarda ve kortikal alandaki glial hücrelerde Aβ ve IL-6 düzeylerinin azaldığı görülmüştür. Sonuçlar: Tosilizumab tedavisinin STZ ile oluşturulan bilişsel bozuklukları ve histopatolojik değişimleri anlamlı ölçüde azalttığı bulunmuştur. Tosilizumab’ın AH üzerindeki koruyucu etkisini araştıran yeni çalışmalara ihtiyaç duyulmaktadır. Anahtar sözcükler: Tosilizumab, Alzheimer, intraserebroventiküler streptozotosin, inflamasyon, öğrenme ve bellek 2.
THE EFFECT OF TOCILIZUMAB IN EXPERIMENTAL ALZHEIMER MODEL Student’s Name: Ersin Aslan bra Elçioğlu Department: Marmara University, Faculty of Pharmacy, Department of Pharmacology Purpose: Neuroinflammation plays a pivotal role in the pathogenesis of Alzheimer’s Disease (AD). It was suggested that IL-6 shows overespression and pleiotropic activity in AD’s brain. Tocilizumab (TCZ) that is a humanized anti-human IL-6 receptor (IL-6R) monoclonal antibody, inhibits IL-6 signal transduction. The aim of our study is to learn that the effect of Tocilizumab on AD cognitive deficits caused by intracerebroventricular (i.c.v.) injection of streptozotocin (STZ). Methods: Male Sprague-Dawley rats were divided into three different groups: control, STZ and TCZ+STZ. Rats that are in STZ and STZ+TCZ groups, were injected single dosed bilaterally i.c.v STZ (3mg/ kg) stereotaxically to induce experimental Alzheimer’s disease. We used single dose of i.c.v. TCZ beginning 1 h prior to injection of STZ for 21 days. Behavioral parameters were evaluated between 15st-21st days, and the rats were sacrificed on day 21st to examine histopathological changes. Histopathological changes were examined using hematoxylin-eosin. Results: STZ injection caused a significant decrease in the mean escape latency in passive avoidance and decreased improvement of performance in Morris water maze tests. Brain sections of TCZ treated rats showed decreased Aβ and IL-6 levels in the neurons and glial cells of cortical area compared to STZ. Conclusion: Tocilizumab treatment attenuated significantly STZ induced cognitive impairment and histopathological changes. Further studies are warranted to investigate more protective effect about Tocilizumab on AD. Tocilizumab, Alzheimer, intracerebroventricular streptozotocin, inflammation, learning and memory
THE EFFECT OF TOCILIZUMAB IN EXPERIMENTAL ALZHEIMER MODEL Student’s Name: Ersin Aslan bra Elçioğlu Department: Marmara University, Faculty of Pharmacy, Department of Pharmacology Purpose: Neuroinflammation plays a pivotal role in the pathogenesis of Alzheimer’s Disease (AD). It was suggested that IL-6 shows overespression and pleiotropic activity in AD’s brain. Tocilizumab (TCZ) that is a humanized anti-human IL-6 receptor (IL-6R) monoclonal antibody, inhibits IL-6 signal transduction. The aim of our study is to learn that the effect of Tocilizumab on AD cognitive deficits caused by intracerebroventricular (i.c.v.) injection of streptozotocin (STZ). Methods: Male Sprague-Dawley rats were divided into three different groups: control, STZ and TCZ+STZ. Rats that are in STZ and STZ+TCZ groups, were injected single dosed bilaterally i.c.v STZ (3mg/ kg) stereotaxically to induce experimental Alzheimer’s disease. We used single dose of i.c.v. TCZ beginning 1 h prior to injection of STZ for 21 days. Behavioral parameters were evaluated between 15st-21st days, and the rats were sacrificed on day 21st to examine histopathological changes. Histopathological changes were examined using hematoxylin-eosin. Results: STZ injection caused a significant decrease in the mean escape latency in passive avoidance and decreased improvement of performance in Morris water maze tests. Brain sections of TCZ treated rats showed decreased Aβ and IL-6 levels in the neurons and glial cells of cortical area compared to STZ. Conclusion: Tocilizumab treatment attenuated significantly STZ induced cognitive impairment and histopathological changes. Further studies are warranted to investigate more protective effect about Tocilizumab on AD. Tocilizumab, Alzheimer, intracerebroventricular streptozotocin, inflammation, learning and memory