THE EFFECTS OF SOCIAL ISOLATION-INDUCED STRESS ON OXIDATIVE STRESS MARKERS AND LEARNING-RELATED NEUROGRANIN/CAMKII/CREB PROTEINS

Year 2025, Volume: 26 Issue: 2, 148 - 155, 28.04.2025

İnci Turan , Hale Sayan Özaçmak

https://doi.org/10.18229/kocatepetip.1540581

Abstract

OBJECTIVE: Social isolation (SI) is an important stress factor for both humans and social animals such as rats. It is known that rats exposed to SI stress show behavioral disorders and their cognitive functions are impaired. The aim of this study is to examine how early period social isolation stress affects learning and memory and changes in synaptic proteins.
MATERIAL AND METHODS: In this study, 20 male Wistar albino rats aged 21 days was used. Rats were randomly divided into 2 groups: 1) Control group (n=10), 2) SI group (n=10). SI was achieved by keeping each rat in different cages for 6 weeks from the first day of weaning on the 21st postnatal day. Control group animals were housed with 3-4 rats in each cage and in standard conditions where social interaction would take place. The Morris water maze (MWM) test was used to assess learning and memory at the end of the 6-week period. At the end of the test, rats were sacrificed and hippocampus tissues were collected. Tissue malondialdehyde (MDA) and reduced glutathione (GSH) levels were determined spectrophotometrically and neurogranin, calcium/calmodulin-dependent Protein kinase II (CaMKII), cyclic AMP (cAMP) Response-Element Binding Protein (CREB) and Brain-Derived Neurotrophic Factor (BDNF) Levels Were Evaluated by ELISA.
RESULTS: There was no difference between the social isolation and control groups in terms of learning and memory in the MWM test. Neurogranin, CaMKII and CREB levels in hippocampus tissue were not different between groups. In the SI group, while hippocampus MDA levels increased, GSH and BDNF levels decreased.
CONCLUSIONS: In our study, it was shown that SI induced-stress for six weeks in post-weaning period increased oxidative stress and decreased BDNF levels and did not change other synaptic proteins in the hippocampus without causing learning and memory impairment.

Keywords

Social Isolation Stress, Learning and Memory, Neurogranin/ CaMKII/CREB Pathway, BDNF.

Project Number

2019-26259946-02

SOSYAL İZOLASYONUN NEDEN OLDUĞU STRESİN OKSİDATİF STRES BELİRTEÇLERİ VE ÖĞRENME İLE İLİŞKİLİ NÖROGRANİN/ CAMKII/CREB PROTEİNLERİNE ETKİSİ

Abstract

AMAÇ: Sosyal izolasyon (Sİ) hem insanlar için hem de ratlar gibi sosyal hayvanlar için önemli bir stres faktörüdür. Sİ stresine maruz kalan ratların davranışsal bozukluklar gösterdiği ve kognitif fonksiyonlarının bozulduğu bilinmektedir. Bu çalışmanın amacı erken dönemde oluşturulan Sİ stresinin öğrenme ve hafızayı nasıl etkilediğini ve sinaptik proteinlerde meydana gelen değişiklikleri incelemektir.
GEREÇ VE YÖNTEM: Çalışmada 21 günlük 20 adet erkek Wistar albino cinsi rat kullanıldı. Ratlar rastgele 2 gruba ayrıldı: 1) Kontrol grubu (n=10), 2) Sİ grubu (n=10). Sİ doğum sonrası 21. günde sütten kesmenin ilk gününden itibaren 6 hafta boyunca her sıçanın farklı kafeslerde barındırılmasıyla gerçekleştirildi. Kontrol grubu hayvanları ise her kafeste 3-4 sıçan olacak şekilde ve sosyal etkileşimin gerçekleşeceği standart koşullarda barındırıldı. 6 haftalık süre sonunda öğrenme ve hafızayı değerlendirmek için Morris su labirent (MWM) testi kullanıldı. Test sonunda ratlar feda edilerek hipokampüs dokuları toplandı. Doku malondialdehid (MDA) ve indirgenmiş glutatyon (GSH) seviyeleri spektrofotometrik olarak ve nörogranin, kalsiyum/kalmodulin bağımlı protein kinaz tip II (CaMKII), Döngüsel AMP (cAMP) cevap elementine bağlanan protein (CREB) ve Beyinden türeyen nörotrofik faktör (BDNF) seviyeleri ELISA ile değerlendirildi.
BULGULAR: Sİ ve kontrol grubu arasında MWM testinde öğrenme ve hafıza açısından fark saptanmadı. Hipokampüs dokusunda nörogranin, CaMKII ve CREB düzeyleri gruplar arasında farklı değildi. Sİ yapılan grupta hipokampüs MDA düzeyi artarken, GSH ve BDNF düzeyleri azaldı.
SONUÇ: Çalışmamızda sütten kesme sonrası oluşturulan altı haftalık Sİ stresinin öğrenme ve hafıza bozukluğuna neden olmadan hipokampüste oksidatif stresi arttırdığı, BDNF düzeylerini düşürdüğü ve diğer sinaptik proteinleri değiştirmediği gösterildi.

Keywords

sosyal izolasyon, öğrenme ve hafıza, Neurogranin

Ethical Statement

Zonguldak Bülent Ecevit Üniversitesi Hayvan Deneyleri Yerel Etik Kurulundan onaylı etik izin belgesi alınmıştır (Protokol no:2019-12-12/09).

Supporting Institution

Zonguldak Bülent Ecevit Üniversitesi Bilimsel Araştırma Projeleri Koordinasyon birimi

Project Number

2019-26259946-02

Thanks

Bu çalışma Zonguldak Bülent Ecevit Üniversitesi Bilimsel Araştırma Projeleri Koordinasyon birimi tarafından desteklenmiştir. (Proje No: 2019-26259946-02)

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