Short-Term Fructose Feeding Induces Inflammation and Oxidative Stress in the Hippocampus of Young and Adult Rats Luisa Cigliano 1 & Maria Stefania Spagnuolo 2 & Raffaella Crescenzo 1 & Rosa Cancelliere 1 & Lucia Iannotta 1 & Arianna Mazzoli 1 & Giovanna Liverini 1 & Susanna Iossa 1 Received: 22 December 2016 /Accepted: 4 April 2017 # Springer Science+Business Media New York 2017 Abstract 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 pre- vious studies investigated brain disturbances induced by long- term fructose feeding in adults. Therefore, we investigated whether a short-term consumption of fructose (2 weeks) pro- duces 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, evi- denced 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 as- sociated with brain oxidative stress, as increased levels of lipid peroxidation and nitro-tyrosine were detected in the hippo- campus. 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 un- balanced 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. Keywords Fructose . Hippocampus . Lipid peroxidation . Mitochondrion . Nitro-tyrosine TNF-alpha Introduction The consumption of fructose has increased drastically over the past two centuries [1], mainly because of consumption of su- crose or high-fructose corn syrup in industrial foods and bev- erages. Fructose may have a role in the development of obe- sity by contributing, together with other nutrients, to an overall excessive energy intake [2]. In addition, a high-fructose intake also increases hepatic de novo lipogenesis, very low-density lipoprotein triglyceride secretion, and intrahepatic fat concen- trations [2]. The fructose-fed rat represents a commonly used animal model for studying diet-induced metabolic distur- bances [3]. Using this experimental animal model, we previ- ously showed that long-term treatment with a fructose-rich diet elicits in adult rats the development of obesity, insulin resistance, and hepatic steatosis [4–6]. We also demonstrated that fructose worsened the deleterious effects of a high-fat diet after just 2 weeks of treatment [7, 8], thus suggesting that even short periods of high-fructose intake may induce metabolic perturbations. In the last decade, attention was focused on the harmful effects of fructose intake on the brain as well. Indeed, long- term high-fructose intake was shown to induce a reduction of * Susanna Iossa susiossa@unina.it 1 Department of Biology, University of Naples Federico II, Naples, Italy 2 Department of Bio-Agrofood Science, Institute for Animal Production System in Mediterranean Environment, National Research Council, Naples, Italy Mol Neurobiol DOI 10.1007/s12035-017-0518-2