Publication: Sıçanlarda kronik öngörülemeyen stres ile oluşturulan depresyon modelinde harmanın rolünün araştırılması
Abstract
Amaç: Depresyonun patofizyolojisi strese maruziyet ve bunu takiben oluşaninflamatuvar yanıtlar ile ilişkilendirilmektedir. Çalışmamızda kronik öngörülemeyenhafif stres (KÖHS) ile depresyon modeli oluşturulan sıçanlarda kronik harmanuygulamasının inflamatuvar yolaklar üzerine etkisinin araştırılması amaçlanmaktadır.Gereç ve Yöntem: Erkek Wistar Albino sıçanlar (220-360 g) Kontrol, KÖHS,KÖHS+Harman 5 (5 mg/ kg), KÖHS+Harman 10 (10 mg/ kg) olmak üzere gruplaraayrılmıştır (n=10-12). Model çeşitli stresörlerin ardışık olmadan 6 hafta süre ileuygulanması ile oluşturulmuş ve 20. günden itibaren iki farklı dozda ve günde bir kereharman uygulanmıştır. Antidepresan etkinliğin değerlendirilmesinde sükroz tercihtesti ve zorunlu yüzme testi kullanılmıştır. İnflamatuvar ve antiinflamatuvar yanıtlarimmünohistokimyasal ve moleküler analizlerle belirlenmiştir.Bulgular: Sükroz tercih testi 5 mg/ kg harman tedavisinde ve zorunlu yüzme testi dehem 5 mg/ kg hem de 10 mg/ kg harman tedavilerinde antidepresan benzeri etkiyigöstermiştir. Moleküler ve immünohistokimyasal inflamatuvar parametrelerdekideğişiklikler gruplar arasında istatistiksel anlamlı farklar ortaya koymuştur. Kaspaz-1,IL-1ß, IL-6 düzeyleri ve Iba-1 mikroglial hücre aktivasyonu KÖHS’e oranla Harman10’da istatistiksel anlamlı azalmıştır. NLRP3, IL-18, ASC ve CD11b gen ekspresyondüzeyleri ise KÖHS’le değişmemiş, tedaviden etkilenmemiştir. Hipokampüs GFAPdüzeyleri ve NF-κB RNA ekspresyon seviyeleri KÖHS’le artmış, harman iledeğişmemiştir. P2X7 reseptör ekspresyonu Harman 5 ile artmış Harman 10 ileazalmıştır. NLRP1 inflamazomu Harman 10 ile artmış olarak bulunmuştur.Sonuçlar: Çalışmalarımızda ortaya çıkan veriler endojen beta-karbolin harmanınkronik öngörülemeyen hafif stres modeli ile depresyon oluşturulan sıçanlarda, depresifbenzeri davranışlarda doza bağlı iyileşmeler sağladığını ortaya koymuştur. Beyindokuları üzerinde yapılan analizlerimiz sonucunda depresyonun gelişiminde artığıgörülen inflamatuvar parametrelerin bazılarının harman ile tedaviye yanıttaistatistiksel anlamda azalma gösterdikleri sonuçlarını vermiştir.
Purpose: The pathophysiology of depression is associated with stress exposure andfollowing inflammatory responses. In our study we aim to investigate the associationbetween inflammatory pathways and chronic harmane therapy on chronicunpredictable mild stress (CUMS) induced depressive rats.Materials and methods: Male Wistar Albino rats (body weight: 220-360 g) wereseperated into four groups as follow: Control, CUMS, CUMS+Harman5 (5 mg/ kg),CUMS+Harman10(10 mg/ kg) (n=10-12). In this model nonconsecutive variousstressors were randomly implemented for 6 weeks and intraperitoneal harmaneadministration was started on 20th day till the end of experiments. In order to detectantidepressant activity of harmane sucrose preference test and forced swim test havebeen performed. Determination of inflammatory and antiinflammatory responses wasvia immunohistochemical and molecular analyses.Findings: Behavioural tests data shows that the chronic administration of harmanecontributes a recovery on depressive symptoms in a dose dependent manner. Sucrosepreference test showed that 5 mg/ kg harmane therapy demonstrates antidepressanteffect and forced swim test results indicate that both 5 mg/ kg and 10 mg/ kg harmanetherapy reverse depressive-like behaviours. Molecular and immunohistochemicalanalysis have shown statistically significant results. Levels of mRNA expression ofcaspase-1, IL-1ß, IL-6 and levels of Iba-1 immunoreactivity are significantly elevatedwith CUMS on PFC are reduced in Harmane10 group. Levels of NLRP3, IL-18, ASCve CD11b gene expression are unchanged with CUMS and are not affected by therapy.Hippocampus levels of GFAP and NF-κB gene expression levels are elevated withCUMS, not affected by harmane therapy. P2X7 gene expression was increased withHarmane5 and decreased with Harmane 10. Levels of NLRP1 iflammasome is foud tobe elevated with Harmane10.Results: The data in our study revealed that an endogenous beta-carboline harmaneindicates antidepressant-like effect on chronic unpredictable mild stress induceddepressive rats in a dose-dependent manner. The analyses performed on brain tissuesdemonstrates that levels of some inflammatory parameters,associated with depression,have shown statistically significant responses to chronic harmane therapy.
Purpose: The pathophysiology of depression is associated with stress exposure andfollowing inflammatory responses. In our study we aim to investigate the associationbetween inflammatory pathways and chronic harmane therapy on chronicunpredictable mild stress (CUMS) induced depressive rats.Materials and methods: Male Wistar Albino rats (body weight: 220-360 g) wereseperated into four groups as follow: Control, CUMS, CUMS+Harman5 (5 mg/ kg),CUMS+Harman10(10 mg/ kg) (n=10-12). In this model nonconsecutive variousstressors were randomly implemented for 6 weeks and intraperitoneal harmaneadministration was started on 20th day till the end of experiments. In order to detectantidepressant activity of harmane sucrose preference test and forced swim test havebeen performed. Determination of inflammatory and antiinflammatory responses wasvia immunohistochemical and molecular analyses.Findings: Behavioural tests data shows that the chronic administration of harmanecontributes a recovery on depressive symptoms in a dose dependent manner. Sucrosepreference test showed that 5 mg/ kg harmane therapy demonstrates antidepressanteffect and forced swim test results indicate that both 5 mg/ kg and 10 mg/ kg harmanetherapy reverse depressive-like behaviours. Molecular and immunohistochemicalanalysis have shown statistically significant results. Levels of mRNA expression ofcaspase-1, IL-1ß, IL-6 and levels of Iba-1 immunoreactivity are significantly elevatedwith CUMS on PFC are reduced in Harmane10 group. Levels of NLRP3, IL-18, ASCve CD11b gene expression are unchanged with CUMS and are not affected by therapy.Hippocampus levels of GFAP and NF-κB gene expression levels are elevated withCUMS, not affected by harmane therapy. P2X7 gene expression was increased withHarmane5 and decreased with Harmane 10. Levels of NLRP1 iflammasome is foud tobe elevated with Harmane10.Results: The data in our study revealed that an endogenous beta-carboline harmaneindicates antidepressant-like effect on chronic unpredictable mild stress induceddepressive rats in a dose-dependent manner. The analyses performed on brain tissuesdemonstrates that levels of some inflammatory parameters,associated with depression,have shown statistically significant responses to chronic harmane therapy.