Fructose consumption reduces hippocampal synaptic plasticity underlying cognitive performance

Pedro Cisternas, Paulina Salazar, Felipe G. Serrano, Carla Montecinos-Oliva, Sebastián B. Arredondo, Lorena Varela-Nallar, Salesa Barja, Carlos P. Vio, Fernando Gomez-Pinilla, Nibaldo C. Inestrosa

Research output: Contribution to journalArticlepeer-review

57 Citations (Scopus)


Metabolic syndrome (MetS) is a global epidemic, which involves a spectrum of metabolic disorders comprising diabetes and obesity. The impact of MetS on the brain is becoming to be a concern, however, the poor understanding of mechanisms involved has limited the development of therapeutic strategies. We induced a MetS-like condition by exposing mice to fructose feeding for 7. weeks. There was a dramatic deterioration in the capacity of the hippocampus to sustain synaptic plasticity in the forms of long-term potentiation (LTP) and long-term depression (LTD). Mice exposed to fructose showed a reduction in the number of contact zones and the size of postsynaptic densities (PSDs) in the hippocampus, as well as a decrease in hippocampal neurogenesis. There was an increase in lipid peroxidation likely associated with a deficiency in plasma membrane excitability. Consistent with an overall hippocampal dysfunction, there was a subsequent decrease in hippocampal dependent learning and memory performance, i.e., spatial learning and episodic memory. Most of the pathological sequel of MetS in the brain was reversed three month after discontinue fructose feeding. These results are novel to show that MetS triggers a cascade of molecular events, which disrupt hippocampal functional plasticity, and specific aspects of learning and memory function. The overall information raises concerns about the risk imposed by excessive fructose consumption on the pathology of neurological disorders.

Original languageEnglish
Pages (from-to)2379-2390
Number of pages12
JournalBiochimica et Biophysica Acta - Molecular Basis of Disease
Issue number11
Publication statusPublished - 1 Nov 2015


  • Diabetes
  • Fructose
  • Metabolic syndrome
  • Neuronal dysfunction

ASJC Scopus subject areas

  • Molecular Medicine
  • Molecular Biology


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