Brain Nrf2 pathway, autophagy, and synaptic function proteins are modulated by a short-term fructose feeding in young and adult rats

Abstract

Objectives: A strong rise of the fructose content in the human diet occurred in the last decade, as corn syrup is widely used as a sweetener for beverages and processed food. Since young people make a widespread consumption of added sugars, we evaluated the effects of a two weeks fructose-rich diet on brain redox homeostasis, autophagy and synaptic plasticity in the cortex of young and adults rats, in order to highlight the early risks to which brain is exposed.

Methods and Results: Short-term fructose feeding was associated with an imbalance of redox homeostasis, as lower amount of Nuclear factor (erythroid derived 2)-like 2, lower activity of Glucose 6-phosphate dehydrogenase and Glutathione reductase, together with lower Glutathione/Oxidized Glutathione ratio, were found in fructose-fed young and adult rats. Fructose-rich diet was also associated with the activation of autophagy, as higher levels of Beclin, LC3 II and P62 were detected in cortex of fructose-fed rats. A diet associated decrease of synaptophysin, synapsin I, and synaptotagmin I, was found in fructose-fed young and adult rats. Interestingly, BDNF amount was significantly lower only in fructose-fed adult rats, while the level of its receptor TrkB decreased in both groups of treated rats. A further marker of brain functioning, Acetylcholinesterase activity, was found increased only in fructose-fed young animals.

Conclusion: Overall, our findings suggest that young rats may severely suffer from the deleterious influence of fructose on brain health as the adults and provide experimental data suggesting the need of targeted nutritional strategies to reduce its amount in foods.

Keywords:

• Fructose diet
• Rat cortex
• Synaptic proteins
• Brain-derived neurotrophic factor
• Redox homeostasis
• Nrf2
• Autophagy

Acknowledgments

The authors thank Dr. Emilia de Santis for skillful management of animal house.

Disclaimer statements

Contributors None.

Funding This work was supported by FIRB-Futuro in Ricerca-Italian Ministry of Education, University and Research (MIUR) [grant number RBFR12QW4I_004].

Conflicts of interest None.

Ethics approval Treatment, housing, and euthanasia of animals met the guidelines set by the Italian Health Ministry. All experimental procedures involving animals were approved by ‘Comitato Etico-Scientifico per la Sperimentazione Animale’ of the University of Naples Federico II and authorized by Italian Health Minister (260/2015-PR). The authors ensure that all steps were taken to minimize the pain and suffering of the animals.

Supplemental data

Supplemental data for this article can be accessed at https://doi.org/10.1080/1028415X.2018.1501532.

ORCID

Paolo Bergamo http://orcid.org/0000-0002-1726-7911

Luisa Cigliano http://orcid.org/0000-0002-5491-9659