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Minocycline reverses diabetes-associated cognitive impairment in rats

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Abstract

Background

Minocycline a tetracycline antibiotic is known for anti-inflammatory and neuroprotective actions. Here we determine the therapeutic potential of minocycline against type 2 diabetes associated cognitive decline in rats.

Methods

High fat diet (HFD) and low dose streptozotocin (STZ; 25 mg/kg) were used to induce diabetes in Sprague-Dawley rats. Fasting blood glucose and haemoglobin (Hb) A1c were measured in these animals. Cognitive parameters were measured using passive avoidance and elevated plus maze test. Hippocampal Acetylcholine esterase (AchE), reduced glutathione (GSH), cytokines, chemokine levels were measured and histopathological evaluations were conducted. The diabetic animals were then given minocycline (50 mg/kg; 15 days) and the above parameters were reassessed. MTT and Lactate dehydrogenase (LDH) assays were conducted on neuronal cells in the presence of glucose with or without minocycline treatment.

Results

We induced diabetes using HFD and STZ in these animals. Animals showed high fasting blood glucose levels (>245 mg/dl) and HbA1c compared to control animals. Diabetes significantly lowered step down latency and increased transfer latency. Diabetic animals showed significantly higher AchE, Tumor necrosis factor (TNF)-α, Interleukin (IL)-1β and Monocyte chemoattractant protein (MCP)-1 and lower GSH levels and reduced both CA1 and CA3 neuronal density compared to controls. Minocycline treatment partially reversed the above neurobehavioral and biochemical changes and improved hippocampal neuronal density in diabetic animals. Cell line studies showed glucosemediated neuronal death, which was considerably reversed upon minocycline treatment.

Conclusions

Minocycline, primarily by its anti-inflammatory and antioxidant actions prevented hippocampal neuronal loss thus partially reversing the diabetes-associated cognitive decline in rats.

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  1. Department of Pharmaceutical Sciences and Technology, Birla Institute of Technology, Mesra, Ranchi, Jharkhand, India

    Bina K. Mehta & Sugato Banerjee

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Correspondence to Sugato Banerjee.

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Mehta, B.K., Banerjee, S. Minocycline reverses diabetes-associated cognitive impairment in rats. Pharmacol. Rep 71, 713–720 (2019). https://doi.org/10.1016/j.pharep.2019.03.012

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