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Title

Resveratrol protects SAMP8 brain under metabolic stress: focus on mitochondrial function and Wnt pathway

AuthorsPalomera-Ávalos, Verónica; Griñán-Ferré, Christian; Puigoriol-Illamola, Dolors; Camins, Antoni; Sanfeliu, Coral CSIC ORCID; Canudas, Anna Maria; Pallàs, Mercè
KeywordsAging
Neurodegeneration
Behaviour
Cognition
Diabetes metabolic stress
Mitochondrial dynamics
Resveratrol
Mitochondria
Fission
Fusion β-catenin
Learning
Issue DateApr-2017
PublisherSpringer
CitationMolecular Neurobiology 54(3): 1661–1676 (2017)
AbstractMetabolic 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.
Publisher version (URL)https://doi.org/10.1007/s12035-016-9770-0
URIhttp://hdl.handle.net/10261/176882
DOI10.1007/s12035-016-9770-0
ISSN0893-7648
E-ISSN1559-1182
Appears in Collections:(IIBB) Artículos

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