Publication: Kronik öngörülemeyen stres modeli oluşturulan sıçanlarda nöropeptit W'nin beyinüzerine olası koruyucu etkilerinin incelenmesi
Abstract
Amaç: Kronik stres hem fizyolojik hem de psikolojik sağlığı ciddi şekilde etkiler ve nörolojik anormalliklere ve hafıza bozukluğuna neden olur. İki (23 ve 30 amino asit) moleküler izoformla tanımlanan nöropeptit W’in (NPW), deneysel çalışmalarda nöronal koruma ve anti-inflamasyon sağladığı öne sürülmüştür. Bu çalışmada, morfolojik, biyokimyasal ve moleküler analizler yoluyla kronik öngörülemeyen stres (KS) modelinde NPW'nin olası nöroprotektif etkileri incelenmiştir. Materyal ve Metot: Sprague Dawley erkek sıçanlar beş gruba (Kontrol, NPW, KS, KS+NPW, KS+Diazepam) ayrıldı. Stresörler 40 gün boyunca rastgele uygulandı. NPW (1 μg/ kg, cilt altı) stresörlerden önce, diazepam (5 mg/ kg) ise KS+Diazepam grubuna uygulandı. Davranış testleri (pasif kaçınma ve açık alan) yapıldı, kan ve beyin örnekleri alındı. Serumda ACTH, kortikosteron, proinflamatuar (IL-1β, IL-6, TNF-α) ve anti-inflamatuar (IL-10) sitokin seviyeleri ELISA ile ölçüldü. NF-κB ve IBA1 seviyeleri Western blot, IL-6, IL-10 ve NR3C1 mRNA ekspresyonları RT-qPCR ile belirlendi. Beyin dokuları H&E, GFAP, BDNF ve NF-kB immünohistokimyası ile incelendi. Veriler One-way ANOVA ve Tukey testiyle analiz edildi. Bulgular: KS grubunda kontrol grubuna kıyasla ACTH, kortikosteron, proinflamatuar sitokinler artmış, anti-inflamatuar sitokinler azalmıştı (p<0,001). NF-κB, IBA1 protein seviyeleri ve IL-6, IL-10, NR3C1 mRNA ekspresyonu artmıştı (p<0,01-p<0,001). Bu parametreler NPW ve diazepam tedavileriyle tersine döndü (p<0,001). KS grubunda gözlenen nörodejenerasyon KS+NPW grubunda azalmıştı (p<0,01). Davranış testleri ve immünohistokimyasal bulgularbiyokimyasal ve morfolojik bulguları desteklemekteydi. Sonuç: Bu sonuçlar, NPW'nin sıçanlarda kronik öngörülemeyen stres modelinde inflamasyonu önleyerek stres kaynaklı nöronal hasara karşı koruyucu bir etki gösterebileceğini göstermektedir. Bu çalışma, kronik stresten kaynaklanan nörolojik bozukluklarda alternatif stratejilerin geliştirilmesi için bir potansiyel olarak nöropeptid W'yi desteklemektedir.
Objective: Chronic stress impacts physiological and psychological health, causing neurological abnormalities and memory impairment. Neuropeptide W (NPW), with two isoforms (23 and 30 amino acids), is suggested to offer neuroprotection and anti-inflammatory effects. This study investigated the neuroprotective potential of NPW in a chronic unpredictable stress (CUS) model through morphological, biochemical, and molecular analyses. Materials and Methods: Male Sprague Dawley rats were divided into five groups (Control, NPW, CUS, CUS+NPW, and CUS+Diazepam). Stressors were applied for 40 days. NPW (1 μg/ kg, subcutaneous) was given before each stressor, and diazepam (5 mg/ kg) to the CUS+Diazepam group. Behavioral tests were conducted, and blood and brain samples were collected. Serum ACTH, corticosterone, cytokines (IL-1β, IL-6, TNF-α, IL-10) were measured via ELISA. NF-κB, IBA1, and mRNA expressions (IL-6, IL-10, NR3C1) were assessed using Western blot and RT-qPCR. Brain tissues were analyzed with H&E staining, GFAP, BDNF and NF-kB immunohistochemistry. Data were analyzed using one-way ANOVA and Tukey's test Results: Compared to the control group, the CUS group exhibited elevated ACTH, corticosterone, and pro-inflammatory cytokine levels, along with decreased anti-inflammatory cytokine levels (p<0.001). Increased NF-κB and IBA1 protein levels and IL-6, IL-10, and NR3C1 mRNA expressions were observed in the CUS group (p<0.01–p<0.001). These parameters were reversed with NPW and diazepam treatments (p<0.001). The neurodegeneration observed in KS groups decreased in KS+NPW members (p<0.01). Behavioral tests and immunohistochemical findings supported the biochemical and morphological results. Conclusion: These findings suggest that NPW exerts a protective effect against stress-induced neuronal damage in a chronic unpredictable stress model by preventing inflammation. This study highlights NPW as a potential therapeutic agent for neurological disorders associated with chronic stress.
Objective: Chronic stress impacts physiological and psychological health, causing neurological abnormalities and memory impairment. Neuropeptide W (NPW), with two isoforms (23 and 30 amino acids), is suggested to offer neuroprotection and anti-inflammatory effects. This study investigated the neuroprotective potential of NPW in a chronic unpredictable stress (CUS) model through morphological, biochemical, and molecular analyses. Materials and Methods: Male Sprague Dawley rats were divided into five groups (Control, NPW, CUS, CUS+NPW, and CUS+Diazepam). Stressors were applied for 40 days. NPW (1 μg/ kg, subcutaneous) was given before each stressor, and diazepam (5 mg/ kg) to the CUS+Diazepam group. Behavioral tests were conducted, and blood and brain samples were collected. Serum ACTH, corticosterone, cytokines (IL-1β, IL-6, TNF-α, IL-10) were measured via ELISA. NF-κB, IBA1, and mRNA expressions (IL-6, IL-10, NR3C1) were assessed using Western blot and RT-qPCR. Brain tissues were analyzed with H&E staining, GFAP, BDNF and NF-kB immunohistochemistry. Data were analyzed using one-way ANOVA and Tukey's test Results: Compared to the control group, the CUS group exhibited elevated ACTH, corticosterone, and pro-inflammatory cytokine levels, along with decreased anti-inflammatory cytokine levels (p<0.001). Increased NF-κB and IBA1 protein levels and IL-6, IL-10, and NR3C1 mRNA expressions were observed in the CUS group (p<0.01–p<0.001). These parameters were reversed with NPW and diazepam treatments (p<0.001). The neurodegeneration observed in KS groups decreased in KS+NPW members (p<0.01). Behavioral tests and immunohistochemical findings supported the biochemical and morphological results. Conclusion: These findings suggest that NPW exerts a protective effect against stress-induced neuronal damage in a chronic unpredictable stress model by preventing inflammation. This study highlights NPW as a potential therapeutic agent for neurological disorders associated with chronic stress.