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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Main Authors: Kewarin Jinawong, Nattayaporn Apaijai, Supawit Wongsuchai, Wasana Pratchayasakul, Nipon Chattipakorn, Siriporn C. Chattipakorn
Format: Journal
Published: 2020
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http://cmuir.cmu.ac.th/jspui/handle/6653943832/70807
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spelling 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
institution Chiang Mai University
building Chiang Mai University Library
continent Asia
country Thailand
Thailand
content_provider Chiang Mai University Library
collection CMU Intellectual Repository
topic Medicine
spellingShingle 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
description © 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.
format Journal
author 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
author_sort 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
publishDate 2020
url 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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