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

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.

• Authors: Gemma Sangüesa, Mar Cascales, Christian Griñán, Rosa María Sánchez, Núria Roglans, Mercè Pallàs, Juan Carlos Laguna, Marta Alegret
• Journal: Molecular neurobiology (Mol Neurobiol) Vol. 55 Issue 8 Pg. 6984-6999 (Aug 2018) ISSN: 1559-1182 [Electronic] United States
• PMID: 29372547 (Publication Type: Journal Article)

Chemical References

• Biomarkers
• Brain-Derived Neurotrophic Factor
• Glycation End Products, Advanced
• Insulin
• Insulin Receptor Substrate Proteins
• RNA, Messenger
• Thiobarbituric Acid Reactive Substances
• Triglycerides
• Fructose
• Glucose

Topics

• Animals
• Biomarkers (metabolism)
• Brain (metabolism)
• Brain-Derived Neurotrophic Factor (metabolism)
• Cognition
• Drinking Behavior
• Female
• Fructose (administration & dosage)
• Glucose (administration & dosage)
• Glucose Tolerance Test
• Glycation End Products, Advanced (blood)
• Hippocampus (metabolism)
• Inflammation (pathology)
• Insulin (blood, metabolism)
• Insulin Receptor Substrate Proteins (genetics, metabolism)
• Insulin Resistance
• Memory
• Mitochondrial Dynamics
• Oxidative Stress
• Prefrontal Cortex (metabolism)
• RNA, Messenger (genetics, metabolism)
• Rats
• Rats, Sprague-Dawley
• Recognition, Psychology
• Signal Transduction
• Thiobarbituric Acid Reactive Substances (metabolism)
• Triglycerides (blood)