Cardiotrophin-1 (CT-1) Improves High Fat Diet-Induced Cognitive Deficits in Mice

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• 作者：Dongmei Wang ; Ling Liu ; Junqiang Yan ; Wenlan Wu ; Xiaoying Zhu…
• 关键词：CT ; 1 ; High fat diet ; Cognitive deficits ; Insulin/IGF signaling ; Neuroinflammation
• 刊名：Neurochemical Research
• 出版年：2015
• 出版时间：April 2015
• 年：2015
• 卷：40
• 期：4
• 页码：843-853
• 全文大小：923 KB
• 参考文献：1. Poirier, P, Giles, TD, Bray, GA, Hong, Y, Stern, JS, Pi-Sunyer, FX, Eckel, RH (2006) Obesity and cardiovascular disease: pathophysiology, evaluation, and effect of weight loss: an update of the 1997 American Heart Association Scientific Statement on Obesity and Heart Disease from the Obesity Committee of the Council on Nutrition, Physical Activity, and Metabolism. Circulation 113: pp. 898-918 CrossRef
  2. Olufadi, R, Byrne, CD (2008) Clinical and laboratory diagnosis of the metabolic syndrome. J Clin Pathol 61: pp. 697-706 CrossRef
  3. Park, EJ, Lee, JH, Yu, GY, He, G, Ali, SR, Holzer, RG, Osterreicher, CH, Takahashi, H, Karin, M (2010) Dietary and genetic obesity promote liver inflammation and tumorigenesis by enhancing IL-6 and TNF expression. Cell 140: pp. 197-208 CrossRef
  4. Ozcan, U, Cao, Q, Yilmaz, E, Lee, AH, Iwakoshi, NN, Ozdelen, E, Tuncman, G, Gorgun, C, Glimcher, LH, Hotamisligil, GS (2004) Endoplasmic reticulum stress links obesity, insulin action, and type 2 diabetes. Science 306: pp. 457-461 CrossRef
  5. Puglielli, L, Tanzi, RE, Kovacs, DM (2003) Alzheimer’s disease: the cholesterol connection. Nat Neurosci 6: pp. 345-351 CrossRef
  6. Casserly, IP, Topol, EJ (2004) Convergence of atherosclerosis and Alzheimer’s disease: cholesterol, inflammation, and misfolded proteins. Discov Med 4: pp. 149-156
  7. Lu, J, Wu, DM, Zheng, YL, Sun, DX, Hu, B, Shan, Q, Zhang, ZF, Fan, SH (2009) Trace amounts of copper exacerbate beta amyloid-induced neurotoxicity in the cholesterol-fed mice through TNF-mediated inflammatory pathway. Brain Behav Immun 23: pp. 193-203 CrossRef
  8. Taghibiglou, C, Bradley, CA, Gaertner, T, Li, Y, Wang, Y, Wang, YT (2009) Mechanisms involved in cholesterol-induced neuronal insulin resistance. Neuropharmacology 57: pp. 268-276 CrossRef
  9. Sinclair, AJ, Girling, AJ, Bayer, AJ (2000) Cognitive dysfunction in older subjects with diabetes mellitus: impact on diabetes self-management and use of care services. All Wales Research into Elderly (AWARE) Study. Diabetes Res Clin Pract 50: pp. 203-212 CrossRef
  10. Schubert, M, Gautam, D, Surjo, D, Ueki, K, Baudler, S, Schubert, D, Kondo, T, Alber, J, Galldiks, N, Kustermann, E (2004) Role for neuronal insulin resistance in neurodegenerative diseases. Proc Natl Acad Sci USA 101: pp. 3100-3105 CrossRef
  11. Craft, S (2005) Insulin resistance syndrome and Alzheimer’s disease: age- and obesity-related effects on memory, amyloid, and inflammation. Neurobiol Aging 26: pp. 65-69 CrossRef
  12. Stranahan, AM, Arumugam, TV, Cutler, RG, Lee, K, Egan, JM, Mattson, MP (2008) Diabetes impairs hippocampal function through glucocorticoid-mediated effects on new and mature neurons. Nat Neurosci 11: pp. 309-317 CrossRef
  13. Stranahan, AM, Norman, ED, Lee, K, Cutler, RG, Telljohann, RS, Egan, JM, Mattson, MP (2008) Diet-induced insulin resistance impairs hippocampal synaptic plasticity and cognition in middle-aged rats. Hippocampus 18: pp. 1085-1088 CrossRef
  14. Felice, FG (2013) Alzheimer’s disease and insulin resistance: translating basic science into clinical applications. J Clin Invest 123: pp. 531-539 CrossRef
  15. Pennica, D, Arce, V, Swanson, TA, Vejsada, R, Pollock, RA, Armanini, M, Dudley, K, Phillips, HS, Rosenthal, A, Kato, AC (1996) Cardiotrophin-1, a cytokine present in embryonic muscle, supports long-term survival of spinal motoneurons. Neuro
• 刊物类别：Biomedical and Life Sciences
• 刊物主题：Biomedicine
  Neurosciences
  Biochemistry
  Neurology
  
• 出版者：Springer Netherlands
• ISSN：1573-6903

文摘

Previous studies demonstrated that a high fat diet (HFD) results in a loss of working memory in mice correlated with neuroinflammatory changes as well as synaptodendritic abnormalities and brain insulin resistance. Cardiotrophin-1 (CT-1), a member of the gp130 cytokine family, has been shown to potentially play a critical role in obesity and the metabolic syndrome. Our recent studies have demonstrated that CT-1 attenuates cognitive impairment and glucose-uptake defects induced by amyloid-β in mouse brain through inhibiting GSK-3β activity. In this study, we evaluated the effect of CT-1 on cognitive impairment induced by brain insulin resistance in mice fed a HFD, and explored its potential mechanism. CT-1 (1?μg/day, intracerebroventricular injection) was given for 14?days to mice that were fed with either a HFD or normal diet for 18?weeks. After 20?weeks of treatment, our results showed that in the HFD group, CT-1 significantly improved learning and memory deficits and alleviated neuroinflammation demonstrated by decreasing brain levels of proinflammatory cytokine tumour necrosis factor-α and interleukin-1β,?and increasing brain levels of?anti-inflammatory cytokine IL-10. CT-1 significantly reduced body weight gain, restored normal levels of blood glucose, fatty acids and cholesterol. Furthermore, CT-1 significantly enhanced insulin/IGF signaling pathway as indicated by increasing the expression levels of insulin receptor substrate 1 (IRS-1) and the phosphorylation of Akt/GSK-3β, and reducing the phosphorylation of IRS-1?in the hippocampus compared to control. Moreover, CT-1 increased the level of the post-synaptic protein, PSD95, and drebrin, a dendritic spine-specific protein in the hippocampus. These results indicate a previously unrecognized potential of CT-1 in alleviating high-fat diet induced cognitive impairment.