Post-Weaning Social Isolation Stress Leads to Behavioral Impairments: A Focus on the Alterations of the Hippocampus and Prefrontal Cortex


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Çelebi G., Göçmez S. S., Duruksu G., Yazır Y., Utkan T.

16th International Congress on Psychopharmacology , Antalya, Türkiye, 23 - 26 Nisan 2025, sa.125, ss.82-85, (Tam Metin Bildiri)

  • Yayın Türü: Bildiri / Tam Metin Bildiri
  • Basıldığı Şehir: Antalya
  • Basıldığı Ülke: Türkiye
  • Sayfa Sayıları: ss.82-85
  • Açık Arşiv Koleksiyonu: AVESİS Açık Erişim Koleksiyonu
  • Kocaeli Üniversitesi Adresli: Evet

Özet

BACKGROUND AND AIM: Previous studies have reported that stressful experiences in early life have a detrimental effect on brain development and may lead to the development of various psychiatric disorders. In the present study, a post-weaned rat model was performed to investigate the effects of chronic social isolation stress exposure on cognitive functions, depression-like, anxiety-like, and obsessive-compulsive-like behaviors in adulthood. The present research also focused on the hippocampus and prefrontal cortex (PFC) to identify potential mechanisms underlying behavioral impairments caused by exposure to social isolation after weaning, a critical period of postnatal brain development.

METHODS: Male Wistar albino rats were randomly assigned to either group rearing or isolation rearing following weaning. The social isolation stress procedure involved housing in individual cages without visual and tactile stimulation throughout the 8-week isolation procedure. Group rearing controls were socially housed with 3 rats/per cage and allowed to maintain visual and tactile contact. Body weights were recorded at the beginning and end of the isolation procedure. At the end of the isolation period, rats were subjected to the locomotor activity test, elevated plus maze test (EPM), forced swimming test (FST), passive avoidance test(PAT), Morris water maze test (MWMT), and marble-burying test (MBT). Following the behavioral tests, hippocampus and PFCsamples were collected under ketamine/xylazine anesthesia. The evaluation BDNF levels in the hippocampus and PFC wasperformed using the ELISA method. The present study employed a quantitative real-time PCR method to examine BDNF, TNF-α,iNOS, SOD-1, HO-1, RAGE, and PPAR-γ gene expression levels in the hippocampus and the prefrontal cortex. The Student’s t-test determined significant differences between groups. Data P≤0.05 was considered significant.

RESULTS: Socially isolated rats showed a statistically significant pattern of anxiety-like, depression-like, and obsessive-compulsive-like behaviors compared to group-rearing controls. These behavioral alterations were evidenced by a decrease in time spent in open arms of EPM test, reflecting anxiety-like behaviors, and an increase in the number of buried marbles, an indicator of repetitive behaviors in MBT. Furthermore, an increase in immobility time and a decrease in struggle time, indicative of hopelessness due to symptoms of depression, were observed in FST. Socially isolated rats also exhibited spatial and emotional memory impairments in MWMT and PAT compared to group-reared rats. Isolation-reared rats have significantly reduced BDNF levels in both brain regions.TNF-α, iNOS, and SOD-1 gene expression levels were found to be significantly increased in the PFC, while RAGE, PPAR-γ, and SOD-1 levels were significantly elevated in the hippocampus. Concurrently, BDNF gene expression levels exhibited a significantincrease in both tissues.

CONCLUSIONS: Present findings suggest that post-weaning social isolation causes behavioral impairments and negatively affects neurogenesis by increasing inflammation and oxidative stress. Additionally, PFC may have a greater vulnerability to social isolation stress-induced inflammation compared to the hippocampus, while demonstrating a higher degree of resistance to oxidative damage. In this regard, it is hypothesized that increasing PPAR-γ levels may compensate the deleterious effects of post-weaning social isolation stress, by augmenting antioxidant capacity. However, increased BDNF gene expression could not protect against social isolation stress in this condition.

Keywords: hippocampus, neuroinflammation, oxidative stress, prefrontal cortex, rat, social isolation stress