Effect of Metabolic Syndrome on Depression in Mice

Abstract:

Metabolic syndrome (MetS) is associated with high blood glucose, insulin resistance, dyslipidemia, central obesity, and hypertension. There is clinical evidence of the coexistence of depression and MetS, however, pathways associating these diseases are far from clear. In the present study, we evaluate and determine the pathogenesis of depression in MetS animals. Methods: Diet induced (High-fat diet long with 20% fructose water; HFHC diet for 4 weeks) MetS was developed in swiss albino mice. Fasting blood glucose levels, Lipids and blood pressure (BP) was measured in these animals. Development of depression in these animals was determined using forced swim and tail suspension tests. This was followed by measurement of GABA, dopamine, serotonin and norepinephrine levels in these animals. We also evaluated the effect of various antidepressants, on MetS associated depression. Results: MetS was induced using high fat and high carbohydrate (HFHC) diet in Swiss albino mice with high fasting blood glucose levels (>250 mg/dl), significantly increased LDL (p<0.001) and triglyceride (p<0.01) and reduced HDL levels (p<0.05) and significant increase in systolic BP; p<0.001) compared to normal controls. MetS animals showed signs of depression with significantly higher (p<0.001) immobility time in forced swim and tail suspension tests. These animals showed significantly lower corticohippocampal norepinephrine (NE) levels (p<0.01) compared to controls. Nortryptaline, showed a dose dependent decrease in immobility time in MetS animals (p<0.001) in both forced swim and tail suspension tests thus reversing MetS induced depression. Conclusion: The above results suggest that MetS may lead to depression in mice which is primarily mediated by NE system. Key words: Depression, Dopamine, Metabolic syndrome, Norepinephrine, Obesity, Serotonin, Type 2 Diabetes.