Hippocampal miR-34a/SIRT1 and BDNF Responses Following Adolescent Stress: Differential Effects of Ketamine and Fluoxetine Ergenlik Dönemi Stresi Sonrasında Hipokampal miR-34a/SIRT1 ve BDNF Yanıtı: Ketamin ve Fluoksetinin Farklı Etkileri
Turk Psikiyatri Dergisi, cilt.37, ss.125-137, 2026 (SSCI, Scopus)
- Yayın Türü: Makale / Tam Makale
- Cilt numarası: 37
- Basım Tarihi: 2026
- Doi Numarası: 10.5080/u27776
- Dergi Adı: Turk Psikiyatri Dergisi
- Derginin Tarandığı İndeksler: Social Sciences Citation Index (SSCI), Scopus, Central & Eastern European Academic Source (CEEAS), MEDLINE, Psycinfo, Biomedical Reference Collection: Corporate Edition (EBSCO), Health Research Premium Collection (ProQuest)
- Sayfa Sayıları: ss.125-137
- Anahtar Kelimeler: Depression, early life stress, fluoxetine, ketamine, miR-34a, SIRT1
- Kütahya Sağlık Bilimleri Üniversitesi Adresli: Evet
Özet
Objective: Early life stress is a well-established risk factor for psychiatric disorders in adulthood; however, the underlying molecular mechanisms remain unclear. This study investigated the effects of chronic unpredictable mild stress (CUMS) starting in adolescence on anxiety- and depression-like behaviors, as well as on hippocampal miR-34a, SIRT1, BDNF, and NLRP3 levels in rats treated with ketamine or fluoxetine. Methods: A total of 40 Wistar albino rats (4 weeks old) were divided into four groups: Control, CUMS, CUMS + fluoxetine (FLU), and CUMS + ketamine (KETA). Chronic unpredictable mild stress was applied for 6 weeks, while fluoxetine (10 mg/kg, i.p.) and ketamine (10 mg/kg, i.p.) were administered during the last 3 weeks. Behavioral assessments were performed at weeks 3 and 6 using the sucrose preference test (SPT), open field test (OFT), and forced swim test (FST). Hippocampal BDNF protein levels were measured by ELISA, and miR-34a, SIRT1, and NLRP3 gene expression levels were analyzed by RT-PCR. Results: Both fluoxetine and ketamine improved CUMS-induced depression-like behaviors. Chronic unpredictable mild stress decreased hippocampal BDNF levels and increased miR-34a expression. Fluoxetine reversed the increase in miR-34a and elevated SIRT1 and BDNF levels. In contrast, although ketamine improved behavioral outcomes, it did not significantly alter hippocampal BDNF or SIRT1 levels and did not reduce miR-34a expression. No significant differences in NLRP3 expression were observed among the groups. Conclusion: Adolescent CUMS induces depression-like behaviors by affecting the hippocampal miR-34a/SIRT1/BDNF axis. While the antidepressant effects of fluoxetine are associated with this axis, ketamine may exert its behavioral effects through different and possibly extra-hippocampal mechanisms. miR-34a may serve as a potential biomarker for depression related to early life stress.