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

• DOI: 10.1007/s10522-013-9461-4
• Publication Date: 2013-10-10T08:27:21Z
• Authors: Maria A. Fiol-deR...; Raquel Gutierrez-...; Silvia Terés; Manuel Torres; Pere Barceló; Rubén V. Rial; Alexei Verkhratsky; Pablo V. Escribá; Xavier Busquets; José J. Rodríguez
• Keywords: Male; 0301 basic medicine; Docosahexaenoic Acids; Neurogenesis; Mice, Transgenic; Amyloid beta-Protein Precursor; Mice; 03 medical and health sciences; Cognition; Alzheimer Disease; Memory; Animals; Humans; 5XFAD Alzheimer model; Maze Learning; Nootropic Agents; Cell Proliferation; Behavior, Animal; Alzheimer's disease; 3. Good health; Disease Models, Animal; Lipid metabolism; Dentate Gyrus; Mutation; 2OHDHA

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.