• Ana Djordjevic, Biljana Bursać, Nataša Veličković, Ana Vasiljević, and Gordana Matić.
• Nutr Neurosci. 2015 Feb 1; 18 (2): 66-75.

ObjectivesHigh fructose diet has been shown to have damaging effects on the hippocampus, a brain region critical for learning and memory. Fructose-induced hippocampal dysfunction may arise from insulin resistance and inflammation, and from concomitant changes in plasticity-related presynaptic proteins. We hypothesized that long-term access to fructose (10% and 60% solutions over a period of 9 weeks) affects insulin sensitivity, hippocampal inflammation, and synaptic plasticity in male Wistar rats.MethodsWe used the area under curve (AUC) glucose value and inhibitory Ser³⁰⁷ phosphorylation of hippocampal insulin receptor substrate 1 (IRS-1) as hallmarks of insulin resistance. To examine inflammatory state, we analysed protein levels and intracellular redistribution of glucocorticoid receptor and nuclear factor-κB (NFκB), as well as mRNA levels of tumour necrosis factor-α (TNF-α), interleukin-6 (IL-6), and interleukin-1β (IL-1β). Polysialylated neural cell adhesion molecule (PSA-NCAM) protein was used as a synaptic plasticity marker.ResultsThe results indicate different impacts of diverse fructose-enriched diets on insulin sensitivity and hippocampal inflammation and plasticity. Long-term ingestion of 10% fructose solution led to increase in AUC glucose value, as well as to elevation in hippocampal IRS-1 Ser³⁰⁷ phosphorylation and increase in IL-6 mRNA. In rats consuming 60% fructose, the level of PSA-NCAM was reduced, in parallel with augmented glucocorticoid signalization.DiscussionThe results showed that long-term consumption of 10% fructose solution induces hippocampal insulin resistance and inflammation, with no concomitant plasticity changes. Interestingly, rats fed with higher concentrations of fructose displayed impaired plastic response of the hippocampus, coinciding with augmented glucocorticoid signalling, which may provide a basis for cognitive deficits associated with metabolic syndrome.

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