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Effect of Metabolic Syndrome on Depression in Mice

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  • Bengal School of Technology (A College of Pharmacy)

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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. © 2018, Association of Pharmaceutical Teachers of India. All rights reserved.
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... Drinking water was supplemented with 20% fructose solution as a source of high carbohydrate in the diet. [16] Assessment of metabolic syndrome Changes in food intake, body weight, waist circumference, blood glucose and lipid levels, and systolic blood pressure were assessed in mice. ...
Article
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.
... Drinking water was supplemented with 20% fructose solution as a source of high carbohydrate in the diet. [16] Assessment of metabolic syndrome Changes in food intake, body weight, waist circumference, blood glucose and lipid levels, and systolic blood pressure were assessed in mice. ...
Article
Full-text available
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.
... Drinking water was supplemented with 20% fructose solution as a source of high carbohydrate in the diet. [16] ...
Article
Full-text available
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.
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