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Chronic Melatonin Administration Reduced Oxidative Damage and Cellular Senescence in the Hippocampus of a Mouse Model of Down Syndrome

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Abstract

Previous studies have demonstrated that melatonin administration improves spatial learning and memory and hippocampal long-term potentiation in the adult Ts65Dn (TS) mouse, a model of Down syndrome (DS). This functional benefit of melatonin was accompanied by protection from cholinergic neurodegeneration and the attenuation of several hippocampal neuromorphological alterations in TS mice. Because oxidative stress contributes to the progression of cognitive deficits and neurodegeneration in DS, this study evaluates the antioxidant effects of melatonin in the brains of TS mice. Melatonin was administered to TS and control mice from 6 to 12 months of age and its effects on the oxidative state and levels of cellular senescence were evaluated. Melatonin treatment induced antioxidant and antiaging effects in the hippocampus of adult TS mice. Although melatonin administration did not regulate the activities of the main antioxidant enzymes (superoxide dismutase, catalase, glutathione peroxidase, glutathione reductase, and glutathione S-transferase) in the cortex or hippocampus, melatonin decreased protein and lipid oxidative damage by reducing the thiobarbituric acid reactive substances (TBARS) and protein carbonyls (PC) levels in the TS hippocampus due to its ability to act as a free radical scavenger. Consistent with this reduction in oxidative stress, melatonin also decreased hippocampal senescence in TS animals by normalizing the density of senescence-associated β-galactosidase positive cells in the hippocampus. These results showed that this treatment attenuated the oxidative damage and cellular senescence in the brain of TS mice and support the use of melatonin as a potential therapeutic agent for age-related cognitive deficits and neurodegeneration in adults with DS.

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Acknowledgments

This work was supported by the Jerome Lejeune Foundation and the Spanish Ministry of Economy and Competitiveness (PSI2012-33652) and by a grant from CAPES/Brazil (proc. 2606/14-13).

Author Contributions

E. B. P. and S. G. performed the experiments. V. V. and S. L. developed the colony and karyotyped the animals. D. W. F. and E. S.-B. discussed the experiments. C. M.-C. and N. R. conceived the project; designed, supervised and interpreted the experiments; analyzed the data; and wrote the manuscript.

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Authors and Affiliations

  1. Department of Ecology and Zoology, Federal University of Santa Catarina, Florianópolis, Brazil

    Eduardo B. Parisotto & Danilo Wilhelm Filho

  2. Laboratory of Neurobiology of Learning, Department of Physiology and Pharmacology, Faculty of Medicine, School of Medicine, University of Cantabria, c/Cardenal Herrera Oria, s/n, 39011, Santander, Spain

    Verónica Vidal, Susana García-Cerro, Sara Lantigua, Emilio J. Sanchez-Barceló, Carmen Martínez-Cué & Noemí Rueda

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  1. Eduardo B. Parisotto
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  2. Verónica Vidal
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  7. Carmen Martínez-Cué
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Correspondence to Noemí Rueda.

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Parisotto, E.B., Vidal, V., García-Cerro, S. et al. Chronic Melatonin Administration Reduced Oxidative Damage and Cellular Senescence in the Hippocampus of a Mouse Model of Down Syndrome. Neurochem Res 41, 2904–2913 (2016). https://doi.org/10.1007/s11064-016-2008-8

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  • DOI: https://doi.org/10.1007/s11064-016-2008-8

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