Minocycline prevents depression‐like behavior in streptozotocin‐induced diabetic mice

Abstract

Diabetes mellitus is a group of metabolic diseases characterized by hyperglycemia. Diabetic patients are known to have a higher prevalence and a higher risk of depression compared with the general population. The pathogenesis of diabetes-related depression is unclear, and the treatment is not well-established. Therefore, the prevention of diabetes-related depression is important for improving the quality of life of diabetic patients. Minocycline, a secondgeneration tetracycline antibiotic, has recently gained attention as a new agent for depression. In this study, we investigated the effect of minocycline on diabetes-related depression in a streptozotocin-induced mouse model of diabetes. Eight-week-old male C57BL/6 mice were injected with streptozotocin (200 mg/kg, i.p.). Seven days after injection, the mice received minocycline treatment through drinking water. We compared these mice with vehicle-treated control mice and diabetic mice not receiving minocycline treatment. On day 34, depression-like behavior was investigated using the forced swim test. On the following day, brain samples were collected, and formalin-fixed, paraffin-embedded specimens were prepared for immunohistochemistry. Compared with the control group, the diabetic mice not receiving minocycline treatment showed a prolonged duration of immobility in the forced swim test, the observation being interpreted as a depression-like behavior. Immunohistochemistry revealed an increase in microglia with an activated morphology in the diabetic mice without minocycline treatment. The expression of tumor necrosis factor alpha in microglia was increased. In addition, a decrease in the number of doublecortin-positive immature neurons was found in the hippocampus of diabetic mice. Minocycline treatment of diabetic animals prevented the depression-like behavior and microglial activation; however, minocycline did not reverse impaired hippocampal neurogenesis. These results indicate that minocycline has a preventive effect on diabetes-related depression. Inhibition of microglial activation would be a critical target for the antidepressant mechanism of minocycline. Impaired hippocampal neurogenesis was observed in diabetic mice; however, this may not be involved in the pathogenesis of depression.

An Eluate of the Medicinal Plant Garcinia kola Displays Strong Antidiabetic and Neuroprotective Properties in Streptozotocin-Induced Diabetic Mice

“…In this study, diabetic control animals displayed marked decreases in body weight and increases in blood sugar level, with motor signs such as significant decreases in the number of efficient steps without tremor (good steps) in the HGT, as well as decreases in time spent on the horizontal grid, possibly due to muscle fatigue associated with the systemic disease [ 40 , 41 ]. Other authors reported similar observations in STZ-induced diabetic rodents [ 42 , 43 ].…”

Effect of Minocycline and Minoscycline+metformin on Diabetes-Related Depression

“…Bu çalışmada, daha önce yapılan çalışmalarla benzer biçimde DM grubunun zorunlu yüzme testinde geçirdiği hareketsiz sürenin kontrol grubuna göre anlamlı olarak arttığı gösterilmiştir [15,17,18].…”

“…Minosiklinin deneysel iskemik felç sonrası meydana gelen depresyon ve anksiyete üzerine etkisinin incelendiği bir çalışmada, minosiklinin (30mg/kg, i.p., 14 gün) lokomotor aktiviteyi değiştirmeksizin antidepresan-benzeri etkiler gösterdiği bildirilmiştir [23]. STZ ile diyabet oluşturulan farelere kronik olarak uygulanan (4 hafta) minosiklinin (100mg/kg, p.o) zorunlu yüzme testinde geçirilen hareketsiz zamanı azalttığı, bu etkinin proinflamatuar sitokin düzeyi ve mikroglial aktivasyonun azalması yolu ile ortaya çıktığı bildirilmiştir [18].Başka bir çalışmada da benzer biçimde STZ uygulanarak diyabet oluşturulan ratlarda kronik minosiklin (80mg/kg, p.o., 3 hafta) tedavisi ile zorunlu yüzme testinde geçirdikleri hareketsiz zamanın azaldığı gösterilmiştir [24].…”

Effect of Minocycline on Depressive Symptoms in Patients With Treatment-Resistant Depression

“…[12][13][14][15] There is profound evidence for antidepressant effects of minocycline in animal models, 16 most likely mediated through beneficial effects on microglial activation. [17][18][19][20] Thus, minocycline treatment has been suggested as a novel antidepressant approach 21 and indeed, a few small randomized clinical trials (RCTs) suggest antidepressant efficacy of minocycline in MDD patients. 22 Emadi-Kouchak and colleagues showed that patients with HIV with mild-to-moderate depression who underwent a 6-week treatment with 100 mg minocycline exhibited larger improvement of depressive symptoms compared with the placebo group.…”

“…Minocycline is a tetracycline antibiotic with pleiotropic antineuroinflammatory properties that readily crosses the blood-brain barrier, inhibits proinflammatory microglial activation, enhances neuroprotective retinoid signaling, and exerts overall neuroprotective effects . There is profound evidence for antidepressant effects of minocycline in animal models, most likely mediated through beneficial effects on microglial activation . Thus, minocycline treatment has been suggested as a novel antidepressant approach and indeed, a few small randomized clinical trials (RCTs) suggest antidepressant efficacy of minocycline in MDD patients .…”