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

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 (A beta) 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 A beta load thus, setting the starting point for the development of a new drug for the treatment of AD.