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Resveratrol Protects SAMP8 Brain Under Metabolic Stress: Focus on Mitochondrial Function and Wnt Pathway

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Abstract

Metabolic stress induced by high-fat (HF) diet leads to cognitive dysfunction and aging, but the physiological mechanisms are not fully understood. Senescence-accelerated prone mouse (SAMP8) models were conducted under metabolic stress conditions by feeding HF for 15 weeks, and the preventive effect of resveratrol was studied. This dietary strategy demonstrates cognitive impairment in SAMP8-HF and significant preventive effect by resveratrol-treated animals. Hippocampal changes in the proteins involved in mitochondrial dynamics optic atrophy-1 protein (OPA1) and mitofusin 2 (MFN2) comprised a differential feature found in SAMP8-HF that was prevented by resveratrol. Electronic microscopy showed a larger mitochondria in SAMP8-HF + resveratrol (SAMP8-HF + RV) than in SAMP8-HF, indicating increases in fusion processes in resveratrol-treated mice. According to the mitochondrial morphology, significant increases in the I-NDUFB8, II-SDNB, III-UQCRC2, and V-ATPase complexes, in addition to that of voltage-dependent anion channel 1 (VDAC1)/porin, were found in resveratrol-treated animals with regard to SAMP8-HF, reaching control-animal levels. Moreover, tumor necrosis factor alpha (TNF-α) and interleukin (IL-6) were increased after HF, and resveratrol prevents its increase. Moreover, we found that the HF diet affected the Wnt pathway, as demonstrated by β-catenin inactivation and modification in the expression of several components of this pathway. Resveratrol induced strong activation of β-catenin. The metabolic stress rendered in the cognitive and cellular pathways altered in SAMP8 focus on different targets in order to act on preventing cognitive impairment in neurodegeneration, and resveratrol can offer therapeutic possibilities for preventive strategies in aging or neurodegenerative conditions.

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Acknowledgments

We thank Maggie Brunner, M.A., for revising the language and style of the manuscript. This study was supported by grant SAF-2012-39852 from the Ministerio de Educación y Ciencia and FEDER founds. P-A V, CG-F, AC, and MP are affiliated with 2014SGR 525 and CIBERNED.

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Authors and Affiliations

  1. Department of Pharmacology, Toxicology and Therapeutic Chemistry (Pharmacology Section) and Institute of Neuroscience, University of Barcelona, Avda. Joan XXIII s/n, 08028, Barcelona, Spain

    V. Palomera-Avalos, C. Griñán-Ferré, D. Puigoriol-Ilamola, A. Camins, A. M. Canudas & M. Pallàs

  2. Institut d’Investigacions Biomèdiques de Barcelona (IIBB), CSIC, and IDIBAPS, 08036, Barcelona, Spain

    C. Sanfeliu

  3. Unitat de Farmacologia i Farmacognòsia, Facultat de Farmàcia, Universitat de Barcelona, Avda. Joan XXIII s/n, 08028, Barcelona, Spain

    M. Pallàs

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  1. V. Palomera-Avalos
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Palomera-Avalos, V., Griñán-Ferré, C., Puigoriol-Ilamola, D. et al. Resveratrol Protects SAMP8 Brain Under Metabolic Stress: Focus on Mitochondrial Function and Wnt Pathway. Mol Neurobiol 54, 1661–1676 (2017). https://doi.org/10.1007/s12035-016-9770-0

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