Yao-Wu Liu1, Xia Zhu2, Liang Zhang2, Qian Lu2, Fan Zhang2, Hao Guo2, Xiao-Xing Yin3. 1. Key Laboratory of New Drugs and Clinical Application, Xuzhou Medical College, Xuzhou 221004, Jiangsu, China; Department of Pharmacology, Nanjing General Hospital of Nanjing Military Command, Nanjing 210002, Jiangsu, China. 2. Key Laboratory of New Drugs and Clinical Application, Xuzhou Medical College, Xuzhou 221004, Jiangsu, China. 3. Key Laboratory of New Drugs and Clinical Application, Xuzhou Medical College, Xuzhou 221004, Jiangsu, China; Department of Pharmacology, Nanjing General Hospital of Nanjing Military Command, Nanjing 210002, Jiangsu, China. Electronic address: yinxx@xzmc.edu.cn.
Abstract
OBJECTIVE: Diabetic encephalopathy is characterised by cognitive impairment, neurochemical and structural abnormalities. The aim of the study was to investigate the effects of ibuprofen on diabetic encephalopathy and potential mechanisms. RESEARCH DESIGN AND METHOD: Diabetes was induced through a single intraperitoneal injection of streptozotocin (60 mg/kg). Diabetic rats were treated with ibuprofen (40 mg/kg) by gavage for 8 weeks. Cognitive performances were evaluated using Morris water maze. The temporal cortex and hippocampus were obtained to evaluate the levels of advanced glycation endproducts (AGEs) and their receptor (RAGE), the activity, protein expression, and mRNA levels of β-amyloid precursor protein cleaving enzyme 1 (BACE1), the protein and mRNA expression of peroxisome proliferator-activated receptor γ (PPARγ), and the protein expression of cyclooxygenase 2 (COX-2) and inducible nitric oxide synthase (iNOS). Blood was obtained for the evaluation of interleukin 1β level. RESULTS: Chronic ibuprofen treatment significantly prevented the decline in learning and memory ability of diabetic rats and loss of neurons in the CA1 and CA3 areas of the hippocampus. Moreover, ibuprofen treatment markedly reduced the activity, protein, and mRNA levels of BACE1, AGE level, protein expression of RAGE, COX-2, and iNOS in the brain, and interleukin 1β level in serum, while increasing the protein and mRNA expression of PPARγ in the brain of diabetic rats. However, ibuprofen had no effects on the hyperglycaemia and the body weight of diabetic rats. CONCLUSION: These findings demonstrated that ibuprofen markedly ameliorated diabetic encephalopathy, potentially reflecting the down-regulation of BACE1, the suppression of the AGE/RAGE axis, and the anti-inflammation in diabetic rat brain.
OBJECTIVE:Diabetic encephalopathy is characterised by cognitive impairment, neurochemical and structural abnormalities. The aim of the study was to investigate the effects of ibuprofen on diabetic encephalopathy and potential mechanisms. RESEARCH DESIGN AND METHOD:Diabetes was induced through a single intraperitoneal injection of streptozotocin (60 mg/kg). Diabeticrats were treated with ibuprofen (40 mg/kg) by gavage for 8 weeks. Cognitive performances were evaluated using Morris water maze. The temporal cortex and hippocampus were obtained to evaluate the levels of advanced glycation endproducts (AGEs) and their receptor (RAGE), the activity, protein expression, and mRNA levels of β-amyloid precursor protein cleaving enzyme 1 (BACE1), the protein and mRNA expression of peroxisome proliferator-activated receptor γ (PPARγ), and the protein expression of cyclooxygenase 2 (COX-2) and inducible nitric oxide synthase (iNOS). Blood was obtained for the evaluation of interleukin 1β level. RESULTS: Chronic ibuprofen treatment significantly prevented the decline in learning and memory ability of diabeticrats and loss of neurons in the CA1 and CA3 areas of the hippocampus. Moreover, ibuprofen treatment markedly reduced the activity, protein, and mRNA levels of BACE1, AGE level, protein expression of RAGE, COX-2, and iNOS in the brain, and interleukin 1β level in serum, while increasing the protein and mRNA expression of PPARγ in the brain of diabeticrats. However, ibuprofen had no effects on the hyperglycaemia and the body weight of diabeticrats. CONCLUSION: These findings demonstrated that ibuprofen markedly ameliorated diabetic encephalopathy, potentially reflecting the down-regulation of BACE1, the suppression of the AGE/RAGE axis, and the anti-inflammation in diabeticrat brain.
Authors: Isabella Caroline da Silva Dias; Bruno Carabelli; Daniela Kaori Ishii; Helen de Morais; Milene Cristina de Carvalho; Luiz E Rizzo de Souza; Silvio M Zanata; Marcus Lira Brandão; Thiago Mattar Cunha; Anete Curte Ferraz; Joice Maria Cunha; Janaina Menezes Zanoveli Journal: Mol Neurobiol Date: 2015-12-15 Impact factor: 5.590