posted on 2020-04-28, 21:30authored byAda AdminAda Admin, Kewarin Jinawong, Nattayaporn Apaijai, Supawit Wongsuchai, Wasana Pratchayasakul, Nipon Chattipakorn, Siriporn C Chattipakorn
Previous
studies show that 12-week
of high-fat diet (HFD) consumption
caused not only prediabetes, but also cognitive decline
and brain pathologies. Recently, necrostatin-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 prediabetic rats. Rats
(n=32) were fed
with either normal diet (ND) or high-fat
diet (HFD) for 20 weeks. At week 13, ND-fed
rats were given a vehicle (n=8) and HFD-fed rats were randomly assigned into 3 subgroups (n=8/subgroup) with vehicle, nec-1 or metformin for 8 weeks. Metabolic parameters, cognitive function,
brain insulin receptor function, synaptic plasticity, dendritic spine density,
microglial morphology, brain mitochondrial function, Alzheimer’s
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 morphology, brain mitochondrial function, 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.
Funding
This work was supported by Thailand Research Fund grants: RTA 6080003 (SCC), TRG6280005 (NA); the NSTDA Research Chair grant from the National Science and Technology Development Agency Thailand (NC), and the Chiang Mai University Center of Excellence Award (NC).