Sıçanlarda Oluşturulan Prenatal Stres Modelinde Parkinson Hastalığı Patogenezinde Rol Oynayan Bazi Proteinlerin Gen Ekspresyon Düzeylerinin İncelenmesi

Year 2024, Issue: Special Issue / International Multidisciplinary Symposium on Drug Research and Development, DRD-2023, 34 - 45, 01.07.2024

İlayda Varol , Ezgi Turunç

https://doi.org/10.52794/hujpharm.1393164

Abstract

Bu çalışma, prenatal stresin (PS) Parkinson hastalığının (PH) gelecekteki başlangıcını nasıl etkileyebileceğini daha iyi anlamak amacıyla gerçekleştirilmiştir. Çalışma için sıçanlarda deksametazon ile indüklenen bir PS modeli oluşturulmuştur. PH patogenezinde rol oynayan tirozin hidroksilaz (TH), α-sinüklein (SNCA), dopamin taşıyıcı (SLC6A3) ve parkin (PRKN) proteinlerinin ekspresyon seviyelerindeki değişiklikler, PS'ye maruz kalan erkek sıçanların serebral korteksinde gerçek zamanlı PCR ile gösterilmiştir. Hamileliklerinin 14. Gününden 21. Gününe kadar, gebe sıçanlara günlük olarak deksametazon veya salin (100 μg/kg ve 1 ml/kg) enjekte edilmiştir. Doğumdan 3 ay sonra, erkek sıçanlara dekapitasyon uygulandı (n=5), serebral korteks diseksiyonu yapıldı. Total RNA kortekslerden izole edildi ve cDNA sentezi için kullanıldı. Gen ekspresyon analizleri ∆∆CT yöntemine göre yapıldı. Gruplar arasındaki istatistiksel farklılıklar Mann-Whitney testi ile analiz edildi. İstatistikler p<0.05 düzeyinde anlamlı kabul edildi. Gebelik boyunca deksametazon maruziyeti TH ve SLC6A3 mRNA düzeylerini anlamlı şekilde arttırmıştır. Deney grupları arasında PRKN ve SNCA mRNA seviyelerinde anlamlı bir fark bulunmamıştır. Sonuç olarak, PS'ye maruz kalan yavrular, TH ve SLC6A3'ün kortikal mRNA seviyelerinde meydana gelen değişimlerden dolayı yetişkinlikte PH'ye daha duyarlı olabilir.

Anahtar Kelimeler: Prenatal stres, Parkinson Hastalığı, Tirozin hidroksilaz, Dopamin taşıyıcı

Keywords

Prenatal stres, Parkinson hastalığı, Tirozin hidroksilaz, Dopamin taşıyıcı

Investigation of Gene Expression Levels of Some Proteins Related to the Pathogenesis of Parkinson's Disease in Rats Exposed to Prenatal Stress

Abstract

IThis study was carried out in order to better understand how prenatal stress (PS)
may affect the future onset of Parkinson’s disease (PD). A dexamethasone-induced
PS model was established in rats for the study. Changes in the expression
levels of tyrosine hydroxylase (TH), α-synuclein (SNCA), dopamine transporter
(SLC6A3), and parkin (PRKN) proteins, which play role in PD pathogenesis,
were demonstrated by real-time PCR in the cerebral cortex of male rats exposed
to PS. From GD 14 to 21, pregnant rats were injected daily with Dex or saline
(100 μg/kg and 1 ml/kg). 3 months after birth, male rats underwent decapitation
(n=5), cerebral cortex dissection was performed. Total RNA was isolated from
cortexes and used for cDNA synthesis. Gene expression analyzes were performed
according to the ΔΔCT method. The statistical differences between groups were
analyzed by the Mann-Whitney test. Statistics were deemed significant at a level
of 0.05. Dex exposure throughout pregnancy significantly increased mRNA levels
of TH and SLC6A3. No significant differences were found in the mRNA levels
of PRKN and SNCA between experimental groups. In conclusion, offspring
exposed to PS may be more susceptible to PD in adulthood through changes in
the cortical mRNA levels of TH and SLC6A3.

Keywords

Prenatal Stress, Parkinson's disease, Tyrosine hyrdoxylase, Dopamine transporter

Ethical Statement

The Ege University Ethics Committee on Animal Experiments approved this study (05/24/2017; Reference No. 2017-023).

Supporting Institution

TÜBİTAK

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