Abstract
Although numerous studies have demonstrated the harmful effect of excessive fructose consumption at the systemic level, there is little information on its effects in the central nervous system. The purpose of the present work was to study the cellular alterations related to oxidative stress and protein quality control systems induced by a high-fructose diet in the brain of Syrian hamsters and their possible attenuation by exogenous melatonin. High-fructose intake induced type II diabetes together with oxidative damage, led to alterations of the unfolded protein response by activating the eIF2α branch, and impaired the macroautophagic machinery in the brain, favoring the accumulation of aggregates labeled for selective degradation and neurodegeneration markers such as β-amyloid (1–42), tau-p-S199, and tau-p-S404. Melatonin attenuated the manifestation of type II diabetes and reduced oxidative stress, deactivated eIF2α, and decreased tau-p-S404 levels in the brain of animals fed a high-fructose diet.
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Acknowledgements
This work was supported by the Instituto de Salud Carlos III (Spanish Ministry of Economy and Competitiveness) under grants RD12/0043/0030, RD12/0043/0017, PI13/02741 and PI17/02009; and the Government of the Principality of Asturias under grant GRUPIN14-071, all of them co-financed by the European Regional Development Fund. J.C.B.M. acknowledges his MSc thesis award from AINDACE (Ayuda a la Investigación del Daño Cerebral) foundation (Spain). M.R.M.G acknowledges her postdoctoral fellowship (2013-2586/001-001-EMA2) from the PUEDES Program (European Commission). Y.P. acknowledges her predoctoral fellow (FI14/00405) from the Instituto de Salud Carlos III (Spanish Ministry of Economy and Competitiveness).
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The Oviedo University Local Animal Care and Use Committee approved the experimental protocol. All experiments were carried out according to the Spanish Government Guide and the European Community Guide for Animal Care.
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Bermejo-Millo, J.C., Guimarães, M.R.M., de Luxán-Delgado, B. et al. High-Fructose Consumption Impairs the Redox System and Protein Quality Control in the Brain of Syrian Hamsters: Therapeutic Effects of Melatonin. Mol Neurobiol 55, 7973–7986 (2018). https://doi.org/10.1007/s12035-018-0967-2
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DOI: https://doi.org/10.1007/s12035-018-0967-2