Metabolic syndrome-associated cognitive decline in mice: Role of minocycline

OBJECTIVE: The objective of the study was to characterize the mechanism associated with metabolic syndrome (MetS)-associated cognitive decline and determine the effect of minocycline on the above condition in mice. MATERIALS AND METHODS: We developed a HFHC diet-induced MetS model in mice. Diagnostic characteristics of MetS including waist circumference, lipid levels, blood pressure, and fasting blood glucose were measured in these Swiss albino mice. Cognitive parameters were measured using passive avoidance and elevated plus maze test. Hippocampal acetylcholine esterase (AchE), reduced glutathione (GSH), and cytokine levels were measured and histopathological evaluation conducted. The MetS animals were administered minocycline (50 mg/kg; 10 days) and the above parameters were measured. RESULTS: We successfully induced MetS using HFHC diet in mice. Animals showed significantly higher fasting blood glucose levels (P < 0.001), systolic blood pressure (P < 0.01), waist circumference (P < 0.001), low-density lipoprotein (P < 0.001), and triglyceride (P < 0.01) and reduced high density lipoprotein levels (P < 0.05) compared to control animals. Both scopolamine and MetS significantly lowered (P < 0.01) step-down latency and increased transfer latency (P < 0.001). MetS animals showed significantly higher AchE (P < 0.001) and tumor necrosis factor-α (P < 0.001) and Interleukin-1 β (P < 0.01) and lower GSH (P < 0.001) levels and reduced both CA1 (P < 0.001) and CA3 (P < 0.01) neuronal density compared to controls. Minocycline treatment partially reversed the above neurobehavioral and biochemical changes and improved hippocampal neuronal density in MetS animals. CONCLUSION: MetS led to hippocampal oxidative stress and neuroinflammatory changes with a corresponding loss of hippocampal neuronal density and cognitive decline. Anti-inflammatory and antioxidant property of minocycline may be responsible for its neuroprotective actions in these animals.