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Cognitive recovery and restoration of cell proliferation in the dentate gyrus in the 5XFAD transgenic mice model of Alzheimer’s disease following 2-hydroxy-DHA treatment

Abstract

Alzheimer’s disease (AD) is the most common neurodegenerative disorder in the elderly. In the last years, abnormalities of lipid metabolism and in particular of docosahexaenoic acid (DHA) have been recently linked with the development of the disease. According to the recent studies showing how hydroxylation of fatty acids enhances their biological activity, here we show that chronic treatment with a hydroxylated derivative of DHA, the 2-hydroxy-DHA (2OHDHA) in the 5XFAD transgenic mice model of AD improves performance in the radial arm maze test and restores cell proliferation in the dentate gyrus, with no changes in the presence of beta amyloid (Aβ) plaques. These results suggest that 2OHDHA induced restoration of cell proliferation can be regarded as a major component in memory recovery that is independent of Aβ load thus, setting the starting point for the development of a new drug for the treatment of AD.

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Acknowledgements

This work was supported by grants from the Spanish Government: TRACE [grant number PET2008/0172-01 (to X.B.)]; INNPACTO [grant number IPT-010000-2010–16 (to X.B.)]; Plan Nacional de I+D+I 2008–2011 and ISCIII-Subdirección General de Evaluación y Fomento de la investigación co-financed by FEDER [grant number PI10/02738 (to J.J.R. and A.V.)]; and the Government of the Basque Country grants [grant numbers AE-2010-1-28, AEGV10/16 and GV-2011111020 (to J.J.R.)]; as well as by [BIO2010-21132 from the MICINN (to P.E.)]. M.A.F-dR was supported by a fellowship from the Govern de les Illes Balears (Conselleria d’Educació, Cultura i Universitats) operational program co-funded by the European Social Fund. M.A.F-dR and M.T. were also recipients of an IPT-Spanish government fellowship.

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Correspondence to Pablo V. Escribá, Xavier Busquets or José J. Rodríguez.

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Fiol-deRoque, M.A., Gutierrez-Lanza, R., Terés, S. et al. Cognitive recovery and restoration of cell proliferation in the dentate gyrus in the 5XFAD transgenic mice model of Alzheimer’s disease following 2-hydroxy-DHA treatment. Biogerontology 14, 763–775 (2013). https://doi.org/10.1007/s10522-013-9461-4

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Keywords

  • Alzheimer’s disease
  • Lipid metabolism
  • 2OHDHA
  • 5XFAD Alzheimer model
  • Cognition
  • Neurogenesis