Sucrose-induced memory deficits

Both prediabetes and type 2 diabetes mellitus - a heterogeneous metabolic disorder with high prevalence rates - are associated with an increased risk for central nervous system disorders. “Diabetic encephalopathy” is a relatively unknown diabetes complication, characterized by electrophysiological, structural, neurochemical and degenerative neuronal changes which lead to cognitive functioning limitations. The hippocampus, a relevant brain region for learning and memory processes, presents a high degree of susceptibility to the adverse environment of diabetes. The purpose of this work was to characterize the cognitive function (learning and memory) along with hippocampal dysfunction in a sucrose-induced insulin resistance/prediabetes animal model. 17-weeks-old male Wistar rats were given free access to a standard chow and divided into two groups: control (Cont) (drinking water) and high-sucrose (HSu) (35 % sucrose solution). The consumption of a 35 % sucrose solution for an extended period of time (9 weeks) resulted in fasting normoglycemia accompanied by hyperinsulinemia and hypertriglyceridemia in a fed state, and insulin resistance associated with impaired glucose tolerance. The sucrose effect on rats learning and memory performance was assessed using the Morris Water-Maze and the Y-Maze tests, which convincingly showed that hippocampus-dependent spatial memory was dramatically impaired on the HSu rats. In order to corroborate the hippocampal dysfunction underlying this memory alterations, the expression of several proteins was determined by Western Blotting including insulin signaling pathway markers (IR-β, IRS-1, IRS-1 pSer636/639, PI3K), synaptic plasticity markers (1-glutamatergic: GluR1, NR1, PSD-95; 2-exocytotic machinery markers: synaptophysin) and neurotoxicity markers (GS, GFAP, RAGE, HNE, TNF-α) .Herein it was found a reduction in IR-β expression for HSu rats compared to Cont. This was not accompanied by changes in basal levels of further insulin signaling molecules: IRS-1 and PI3K. The results also showed an upregulation of both AMPA and NMDA receptor subunits GluR1 and NR1, respectively, which were not accompanied by a neurotoxic phenotype. Overall, we found that 9 weeks of sucrose consumption resulted in a metabolic condition suggestive of a prediabetic state, which translated into a deficit of rats’ memory performance, accompanied by altered insulin receptor expression as well as altered glutamatergic synapses.