EFFECT OF MINOCYCLINE AND MINOSCYCLINE+METFORMIN ON EXPERIMENTAL DIABETES-RELATED DEPRESSION

Abstract

Objective: Minocycline is a second-generation tetracycline group antibiotic that acts on the central nervous system. Minocycline reduces microglial activation and has anti-inflammatory, anti-apoptotic, and antioxidant properties. Recently, it has been proposed that there is a bidirectional relationship between diabetes and depression and that inflammation is one of the common pathways in their pathophysiology. The effects of minocycline on depression were then investigated. This study aimed to reveal the effects of minocycline alone or in combination with metformin, which is used in the treatment of diabetes, on diabetes-related depression.

Material and Method: For this purpose, to establish a human-like type 2 diabetes model in mice, streptozotocin (STZ) (50mg/kg) was administered once a day for five consecutive days after a 4-week high-fat diet. Animals with blood glucose levels ≥200 mg/dl were considered diabetic and employed in this experiment. Minocycline (40 mg/kg), fluoxetine (20 mg/kg), and metformin (200 mg/kg) were given once a day for 7 days two weeks after STZ injection. After the drug injections were completed, an open field test was used to determine locomotor activity and a forced swimming test was used to determine depression level.

Result and Discussion: It was concluded that diabetes and the drugs administered did not induce a significant change in locomotor activity, and that the minocycline and minocycline-metformin combination was at least as effective as fluoxetine in treating depression. It is recognized that the initiation of antidepressant effects in a short period is critical for patient adherence to therapy and diabetes prognosis. In conclusion, antidepressant-like effects of subchronic minocycline treatment appear to be potent as classical antidepressants. The mechanisms underlying minocycline's effects on mood should be broadly investigated to increase our understanding of depression and unveil potential novel therapies in depression management.

Keywords

• Depression
• diabetes
• minocycline

DENEYSEL DİYABETİN NEDEN OLDUĞU DEPRESYON TEDAVİSİNDE MİNOSİKLİN VE MİNOSİKLİN+METFORMİN KULLANIMI

Abstract

Amaç: Minosiklin, santral sinir sistemine geçebilen, ikinci kuşak tetrasiklin grubu bir antibiyotiktir. Minosiklinin anti-inflamatuar, mikroglial aktivasyonu azaltma, anti-apoptotik, antioksidan özellikleri olduğu bilinmektedir. Son yıllarda diyabet ve depresyon arasında çift yönlü bir ilişki olduğunun ve fizyopatolojilerinde ortak yolaklardan birinin inflamasyon olduğunun ileri sürülmesi ile minosiklinin depresyon üzerine etkileri çalışılmaya başlanmıştır. Bu çalışmada minosiklinin tek başına ve diyabet tedavisinde kullanılan metformin ile kombinasyonu şeklinde kullanımının, diyabet ile ilişkili depresyon üzerine etkilerinin ortaya konması amaçlandı.

Gereç ve Yöntem: Farelerde insandakine benzer tip 2 diyabet modeli oluşturmak için 4 haftalık yüksek kalorili diyetin ardından ardışık beş gün, günde 1 defa streptozotosin (50mg/kg) uygulandı, uygulamadan 1 hafta sonra açlık kan glukoz düzeyi 200 mg/dl’nin üzerinde olan deneklerde diyabetin oluştuğu kabul edilip deneye dahil edildi. Streptozotosin (STZ) enjeksiyonundan iki hafta sonra minosiklin (40mg/kg), fluoksetin (20mg/kg) ve metformin (200mg/kg) 7 gün süre ile günde bir defa uyguladı. İlaç uygulamaları tamamlandıktan sonra; lokomotor aktivitenin belirlenmesi için açık alan testi, depresyon düzeyinin belirlenmesi için zorunlu yüzme testi yapıldı.

Sonuç ve Tartışma: Diyabetin ve uygulanan ilaçların lokomotor aktivitede anlamlı bir değişiklik oluşturmadığı, minosiklin ve minosiklin-metformin kombinasyonunun ise depresyon tedavisinde en az fluoksetin kadar etkili olduğu sonucuna varıldı. Antidepresan etkinin kısa sürede başlamasının hastanın tedaviye uyuncu ve diyabetin prognozu açısından oldukça önemli olduğu bilinmektedir. Bu nedenle de minosiklin uygulamasının gösterdiği antidepresan etki üzerine yapılan çalışmalar derinleştirilmeli, etkinin mekanizması araştırılmalıdır.

Keywords

• Depresyon
• diyabet
• minosiklin

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