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Molecular Neurobiology

, Volume 55, Issue 8, pp 6984–6999 | Cite as

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

  • Gemma Sangüesa
  • Mar Cascales
  • Christian Griñán
  • Rosa María Sánchez
  • Núria Roglans
  • Mercè Pallàs
  • Juan Carlos LagunaEmail author
  • Marta AlegretEmail author
Article

Abstract

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.

Keywords

Simple sugars Cognitive deficit Frontal cortex Hippocampus Metabolic dysfunctions 

Notes

Acknowledgements

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.

Funding Information

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.

Supplementary material

12035_2017_863_MOESM1_ESM.docx (21 kb)
Supplemental Table 1 (DOCX 21 kb)
12035_2017_863_MOESM2_ESM.docx (20 kb)
Supplemental Table 2 (DOCX 20 kb)

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Authors and Affiliations

  1. 1.Department of Pharmacology, Toxicology and Therapeutic Chemistry, School of Pharmacy and Food SciencesUniversity of BarcelonaBarcelonaSpain
  2. 2.CIBER Enfermedades Neurodegenerativas (CIBERNED)Instituto de Salud Carlos III (ISCIII)MadridSpain
  3. 3.Institute of BiomedicineUniversity of BarcelonaBarcelonaSpain
  4. 4.CIBER Fisiología de la Obesidad y Nutrición (CIBEROBN)Instituto de Salud Carlos III (ISCIII)MadridSpain

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