Necrostatin-1 mitigates cognitive dysfunction in prediabetic rats with no alteration in insulin sensitivity
© 2020 by the American Diabetes Association. Previous studies showed that 12 weeks of high-fat diet (HFD) consumption caused not only prediabetes but also cognitive decline and brain pathologies. Recently, necros-tatin-1 (nec-1), a necroptosis inhibitor, showed beneficial effects in brain against st...
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th-cmuir.6653943832-708072020-10-14T08:41:48Z Necrostatin-1 mitigates cognitive dysfunction in prediabetic rats with no alteration in insulin sensitivity Kewarin Jinawong Nattayaporn Apaijai Supawit Wongsuchai Wasana Pratchayasakul Nipon Chattipakorn Siriporn C. Chattipakorn Medicine © 2020 by the American Diabetes Association. Previous studies showed that 12 weeks of high-fat diet (HFD) consumption caused not only prediabetes but also cognitive decline and brain pathologies. Recently, necros-tatin-1 (nec-1), a necroptosis inhibitor, showed beneficial effects in brain against stroke. However, the comparative effects of nec-1 and metformin on cognition and brain pathologies in prediabetes have not been investigated. We hypothesized that nec-1 and metformin equally attenuated cognitive decline and brain pathologies in pre-diabetic rats. Rats (n = 32) were fed with either normal diet (ND) or HFD for 20 weeks. At week 13, ND-fed rats were given a vehicle (n = 8) and HFD-fed rats were randomly assigned into three subgroups (n = 8/subgroup) with ve-hicle, nec-1, or metformin for 8 weeks. Metabolic param-eters, cognitive function, brain insulin receptor function, synaptic plasticity, dendritic spine density, microglial mor-phology, brain mitochondrial function, Alzheimer protein, and cell death were determined. HFD-fed rats exhibited prediabetes, cognitive decline, and brain pathologies. Nec-1 and metformin equally improved cognitive function, synaptic plasticity, dendritic spine density, microglial mor-phology, and brain mitochondrial function and reduced hyperphosphorylated Tau and necroptosis in HFD-fed rats. Interestingly, metformin, but not nec-1, improved brain insulin sensitivity in those rats. In conclusion, necroptosis inhibition directly improved cognition in prediabetic rats without alteration in insulin sensitivity. 2020-10-14T08:41:48Z 2020-10-14T08:41:48Z 2020-07-01 Journal 1939327X 00121797 2-s2.0-85086771033 10.2337/db19-1128 https://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=85086771033&origin=inward http://cmuir.cmu.ac.th/jspui/handle/6653943832/70807 |
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Medicine Kewarin Jinawong Nattayaporn Apaijai Supawit Wongsuchai Wasana Pratchayasakul Nipon Chattipakorn Siriporn C. Chattipakorn Necrostatin-1 mitigates cognitive dysfunction in prediabetic rats with no alteration in insulin sensitivity |
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© 2020 by the American Diabetes Association. Previous studies showed that 12 weeks of high-fat diet (HFD) consumption caused not only prediabetes but also cognitive decline and brain pathologies. Recently, necros-tatin-1 (nec-1), a necroptosis inhibitor, showed beneficial effects in brain against stroke. However, the comparative effects of nec-1 and metformin on cognition and brain pathologies in prediabetes have not been investigated. We hypothesized that nec-1 and metformin equally attenuated cognitive decline and brain pathologies in pre-diabetic rats. Rats (n = 32) were fed with either normal diet (ND) or HFD for 20 weeks. At week 13, ND-fed rats were given a vehicle (n = 8) and HFD-fed rats were randomly assigned into three subgroups (n = 8/subgroup) with ve-hicle, nec-1, or metformin for 8 weeks. Metabolic param-eters, cognitive function, brain insulin receptor function, synaptic plasticity, dendritic spine density, microglial mor-phology, brain mitochondrial function, Alzheimer protein, and cell death were determined. HFD-fed rats exhibited prediabetes, cognitive decline, and brain pathologies. Nec-1 and metformin equally improved cognitive function, synaptic plasticity, dendritic spine density, microglial mor-phology, and brain mitochondrial function and reduced hyperphosphorylated Tau and necroptosis in HFD-fed rats. Interestingly, metformin, but not nec-1, improved brain insulin sensitivity in those rats. In conclusion, necroptosis inhibition directly improved cognition in prediabetic rats without alteration in insulin sensitivity. |
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Kewarin Jinawong Nattayaporn Apaijai Supawit Wongsuchai Wasana Pratchayasakul Nipon Chattipakorn Siriporn C. Chattipakorn |
author_facet |
Kewarin Jinawong Nattayaporn Apaijai Supawit Wongsuchai Wasana Pratchayasakul Nipon Chattipakorn Siriporn C. Chattipakorn |
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Kewarin Jinawong |
title |
Necrostatin-1 mitigates cognitive dysfunction in prediabetic rats with no alteration in insulin sensitivity |
title_short |
Necrostatin-1 mitigates cognitive dysfunction in prediabetic rats with no alteration in insulin sensitivity |
title_full |
Necrostatin-1 mitigates cognitive dysfunction in prediabetic rats with no alteration in insulin sensitivity |
title_fullStr |
Necrostatin-1 mitigates cognitive dysfunction in prediabetic rats with no alteration in insulin sensitivity |
title_full_unstemmed |
Necrostatin-1 mitigates cognitive dysfunction in prediabetic rats with no alteration in insulin sensitivity |
title_sort |
necrostatin-1 mitigates cognitive dysfunction in prediabetic rats with no alteration in insulin sensitivity |
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2020 |
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https://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=85086771033&origin=inward http://cmuir.cmu.ac.th/jspui/handle/6653943832/70807 |
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