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Título

Neuroprotective effects of resveratrol in a high-fat diet-fed Alzheimer's deisease mouse model

AutorGatius, Alaó CSIC ORCID; Sarroca, Sara CSIC; Sanfeliu, Coral CSIC ORCID; Corpas, Rubén CSIC ORCID
Fecha de publicación12-nov-2018
CitaciónXI Simposi de Neurobiologia (2018)
ResumenOver the last decades there has been an over consumption of foods rich in animal fats and refined carbohydrates that has led to an obesity pandemic. Obesity increases the risk of many chronic diseases including Alzheimer’s disease (AD). Nevertheless, reducing caloric intake has showed to delay age-related diseases and the natural compound resveratrol has emerged as a potent mimetic of this caloric restriction. The mechanisms underlying both effects are not fully understood and, as potential therapeutic targets, need to be thoroughly analyzed. To this end, we have analyzed molecular pathways involved in memory loss in mice as a result of a high-fat diet (HFD) administration and the role that resveratrol supplementation on this diet may play. We have focused on 6-months-old 5XFAD mice, which are transgenic AD mice with high amyloid burden, and wild type (WT) mice. Both mice strains fed with HFD showed impairment of recognition memory but when resveratrol was added to the HFD, recognition memory was restored. Moreover, our results indicate that HFD boosts amyloid pathology in both, WT and 5XFAD mice, mainly through the potentiation of the amyloidogenic pathway and the mitigation of the non-amyloidogenic one. Namely, we identified an increase in β-secretase 1 protein levels in the cerebral cortex of both strains after HFD administration. Tau pathology was as well aggravated in both strains, showing increased levels of hyperphosphorylated tau. Interestingly, HFD altered the functionality of the ubiquitin-proteasome system, being the most significant changes the induction of proteasome caspase-like and chymotrypsin-like activities that could not prevent the higher accumulation of ubiquitin-tagged proteins for degradation. Remarkably, resveratrol demonstrated the capability to normalize all the pathological changes induced by the HFD in both WT and 5XFAD mice, confirming its preventive and therapeutic potential against neurodegeneration.
DescripciónTrabajo presentado en el XI Simposi de Neurobiologia: Future technical advances, organizado por la Socitat Catalana de Biologia, en Barcelona, los días 12 y 13 de noviembre de 2018
URIhttp://hdl.handle.net/10261/177637
Aparece en las colecciones: (IIBB) Comunicaciones congresos




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