Molecular Neurobiology

, Volume 55, Issue 4, pp 2869–2883 | Cite as

Short-Term Fructose Feeding Induces Inflammation and Oxidative Stress in the Hippocampus of Young and Adult Rats

  • Luisa Cigliano
  • Maria Stefania Spagnuolo
  • Raffaella Crescenzo
  • Rosa Cancelliere
  • Lucia Iannotta
  • Arianna Mazzoli
  • Giovanna Liverini
  • Susanna Iossa


The drastic increase in the consumption of fructose encouraged the research to focus on its effects on brain physio-pathology. Although young and adults differ largely by their metabolic and physiological profiles, most of the previous studies investigated brain disturbances induced by long-term fructose feeding in adults. Therefore, we investigated whether a short-term consumption of fructose (2 weeks) produces early increase in specific markers of inflammation and oxidative stress in the hippocampus of young and adult rats. After the high-fructose diet, plasma lipopolysaccharide and tumour necrosis factor (TNF)-alpha were found significantly increased in parallel with hippocampus inflammation, evidenced by a significant rise in TNF-alpha and glial fibrillar acidic protein concentrations in both the young and adult groups. The fructose-induced inflammatory condition was associated with brain oxidative stress, as increased levels of lipid peroxidation and nitro-tyrosine were detected in the hippocampus. The degree of activation of the protein kinase B, extracellular signal-regulated kinase 1/2, and insulin receptor substrate 1 pathways found in the hippocampus after fructose feeding indicates that the detrimental effects of the fructose-rich diet might largely depend on age. Mitochondrial function in the hippocampus, together with peroxisome proliferator-activated receptor gamma coactivator 1-alpha content, was found significantly decreased in fructose-treated adult rats. In vitro studies with BV-2 microglial cells confirmed that fructose treatment induces TNF-alpha production as well as oxidative stress. In conclusion, these results suggest that unbalanced diet, rich in fructose, may be highly deleterious in young people as in adults and must be strongly discouraged for the prevention of diet-associated neuroinflammation and neurological diseases.


Fructose Hippocampus Lipid peroxidation Mitochondrion Nitro-tyrosine TNF-alpha 



This work was supported by a grant from the University of Naples Federico II—Ricerca Dip 2015—and by a FIRB-Futuro in Ricerca grant (RBFR12QW4I_004) from the Italian Ministry of Education, University and Research (MIUR). The authors wish to thank Dr. Emilia de Santis for the skillful management of the animal house.

Compliance with Ethical Standards

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.

Conflict of Interest

The authors declare that they have no conflict of interest.


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© Springer Science+Business Media New York 2017

Authors and Affiliations

  1. 1.Department of BiologyUniversity of Naples Federico IINaplesItaly
  2. 2.Department of Bio-Agrofood Science, Institute for Animal Production System in Mediterranean EnvironmentNational Research CouncilNaplesItaly

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