Impairment of Novel Object Recognition Memory and Brain Insulin Signaling in Fructose- but Not Glucose-Drinking Female Rats


Excessive sugar intake has been related to cognitive alterations, but it remains unclear whether these effects are related exclusively to increased energy intake, and the molecular mechanisms involved are not fully understood. We supplemented Sprague-Dawley female rats with 10% w/v fructose in drinking water or with isocaloric glucose solution for 7 months. Cognitive function was assessed through the Morris water maze (MWM) and the novel object recognition (NOR) tests. Plasma parameters and protein/mRNA expression in the frontal cortex and hippocampus were determined. Results showed that only fructose-supplemented rats displayed postprandial and fasting hypertriglyceridemia (1.4 and 1.9-fold, p < 0.05) and a significant reduction in the discrimination index in the NOR test, whereas the results of the MWM test showed no differences between groups. Fructose-drinking rats displayed an abnormal glucose tolerance test and impaired insulin signaling in the frontal cortex, as revealed by significant reductions in insulin receptor substrate-2 protein levels (0.77-fold, p < 0.05) and Akt phosphorylation (0.72-fold, p < 0.05), and increased insulin-degrading enzyme levels (1.86-fold, p < 0.001). Fructose supplementation reduced the expression of antioxidant enzymes and altered the amount of proteins involved in mitochondrial fusion/fission in the frontal cortex. In conclusion, cognitive deficits induced by chronic liquid fructose consumption are not exclusively related to increased caloric intake and are correlated with hypertriglyceridemia, impaired insulin signaling, increased oxidative stress and altered mitochondrial dynamics, especially in the frontal cortex.

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We are a Consolidated Research Group of the Autonomous Government of Catalonia (SGR13-00066). We would like to thank the University of Barcelona’s Language Advisory Service for revising the manuscript.


This study was supported by the Fundació Privada Catalana de Nutrició i Lípids, Ministry of Economy and Competitiveness (grant number SAF2013-42982-R) and European Commission FEDER funds. Miguel Baena and Gemma Sangüesa were supported by FPI and FPU grants from the Spanish Ministry of Science and Innovation.

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Correspondence to Juan Carlos Laguna or Marta Alegret.

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Sangüesa, G., Cascales, M., Griñán, C. et al. Impairment of Novel Object Recognition Memory and Brain Insulin Signaling in Fructose- but Not Glucose-Drinking Female Rats. Mol Neurobiol 55, 6984–6999 (2018).

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  • Simple sugars
  • Cognitive deficit
  • Frontal cortex
  • Hippocampus
  • Metabolic dysfunctions