title: Fructose consumption reduces hippocampal synaptic plasticity underlying cognitive performance.
abstract: 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 7weeks. 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.
authors: Centro de Envejecimiento y Regeneración (CARE), Facultad de Ciencias Biológicas, Pontificia Universidad Católica de Chile, Santiago, Chile.
authors: Pedro
authors: P
authors: Cisternas
authors: Centro de Envejecimiento y Regeneración (CARE), Facultad de Ciencias Biológicas, Pontificia Universidad Católica de Chile, Santiago, Chile.
authors: Paulina
authors: P
authors: Salazar
authors: Centro de Envejecimiento y Regeneración (CARE), Facultad de Ciencias Biológicas, Pontificia Universidad Católica de Chile, Santiago, Chile.
authors: Felipe G
authors: FG
authors: Serrano
authors: Centro de Envejecimiento y Regeneración (CARE), Facultad de Ciencias Biológicas, Pontificia Universidad Católica de Chile, Santiago, Chile.
authors: Carla
authors: C
authors: Montecinos-Oliva
authors: Center for Biomedical Research, Faculty of Biological Sciences and Faculty of Medicine, Universidad Andres Bello, Santiago, Chile.
authors: Sebastián B
authors: SB
authors: Arredondo
authors: Center for Biomedical Research, Faculty of Biological Sciences and Faculty of Medicine, Universidad Andres Bello, Santiago, Chile.
authors: Lorena
authors: L
authors: Varela-Nallar
authors: Departamento de Pediatria, Facultad de Medicina, Pontificia Universidad Católica de Chile, Santiago, Chile.
authors: Salesa
authors: S
authors: Barja
authors: Centro de Envejecimiento y Regeneración (CARE), Facultad de Ciencias Biológicas, Pontificia Universidad Católica de Chile, Santiago, Chile.
authors: Carlos P
authors: CP
authors: Vio
authors: Department of Integrative Biology and Physiology, University of California, Los Angeles, CA, USA.
authors: Fernando
authors: F
authors: Gomez-Pinilla
authors: Centro de Envejecimiento y Regeneración (CARE), Facultad de Ciencias Biológicas, Pontificia Universidad Católica de Chile, Santiago, Chile; Centre for Healthy Brain Ageing, School of Psychiatry, Faculty of Medicine, University of New South Wales, Sydney, Australia; Centro de Excelencia en Biomedicina de Magallanes (CEBIMA), Universidad de Magallanes, Punta Arenas, Chile; Centro UC Síndrome de Down, Pontificia Universidad Católica de Chile, Santiago, Chile. Electronic address: ninestrosa@bio.puc.cl.
authors: Nibaldo C
authors: NC
authors: Inestrosa
keywords: Diabetes; Fructose; Metabolic syndrome; Neuronal dysfunction