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: | , , , , , |
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| Format: | Journal |
| Published: |
2020
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| Subjects: | |
| Online Access: | 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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| Institution: | Chiang Mai University |
| Summary: | © 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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