Characterization of Cognitive Impairment in Type 2 Diabetic Rats

Abstract

Among all the secondary complications of type 2 diabetes, cognitive impairment associated with diabetes is less well studied and characterized. We made an attempt to investigate the molecular mechanisms involved in cognitive decline in high fat diet-streptozotocin model of type 2 diabetes. High-fat diet and a single low dose streptozotocin (25 mg/kg) were used to induce diabetes in Sprague-Dawley rats. Developments of cognitive deficit in these animals were measured using change in transfer latency in elevated plus maze test and stepdown latency in passive avoidance test. This was followed by biochemical estimation of acetylcholinesterase and reduced glutathione levels followed by histological evaluation of cortical and hippocampal slices. The high fat diet-streptozotocin animals developed type 2 diabetes, characterized by an increase in fasting blood glucose levels >250 mg/kg, marked increase (P<0.001) in triglyceride (207±7.2) and total cholesterol level (125.3±2.7) with a decrease (P<0.001) in high-density lipoproteins (14.27±1.1) when compared to control animals. After 4 weeks of development of type 2 diabetes high fat diet-streptozotocin animals showed signs of cognitive deficit with a significant decline in step-down latency (P<0.001) and a significant increase in transfer latency (P<0.001) compared to controls. The high fat diet-streptozotocin animals also showed significant decrease (P<0.001) in cortico-hippocampal glutathione levels and increase in (P<0.001) acetylcholinesterase activity as compared to control animals suggesting type 2 diabetes-associated oxidative stress and decrease in hippocampal Ach activity. Immunohistochemical studies in these animals showed pronounced astrogliosis and microglial activation in the cortical and hippocampal slices suggesting neuroinflammatory changes. We also found significant loss (P<0.001) of hippocampal neurons at CA1 and CA3 region in the diabetic rats as compared with healthy controls. Antidiabetic compound glibenclamide (10 mg/kg for 3 weeks) partly reversed the above neurobehavioral, biochemical and histological changes in the diabetic rat brain. Hence we show that high fat diet-streptozotocin type 2 diabetic rats may develop signs of cognitive impairment. This cognitive decline was found to be associated with an increase in acetylcholinesterase activity and loss of hippocampal neurons. Oxidative stress and neuroinflammatory changes in the brain of these animals may be responsible for hippocampal neuronal loss, which could be partly reversed upon glibenclamide treatment.

Ultrasonic Testing of Clinical Effect of Bicyclol on Liver Function Impairment Induced by Antithyroid Drugs

“…Bicyclol, a novel type synthetic antihepatitic drug can control the elevation of aminotransferase induced by chronic hepatitis. For other liver diseases such as cirrhosis, liver fibrosis, drug-induced hepatitis, Bicyclol reduced the liver function impairment induced by antithyroid drugs, which is in line with studies reported [10][11][12][13][14][15] .…”

Treating Chronic Hepatitis B Liver Fibrosis with a Combination of Biejiaruangan Compound Tablet and Entecavir with the aid of Real-time Shear Wave Elastography

“…Application of RTSWE can prevent 50-60 % of patients from undergoing liver puncture. This study proved that the research group had better liver stiffness, liver function indexes and liver fibrosis indexes than the control group, which is consistent with the relevant findings [9][10][11][12][13][14][15] (Tables 1 and 2). RTSWE could accurately determine the degree of liver fibrosis.…”

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

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