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Publication : The hydroxylated form of docosahexaenoic acid (DHA-H) modifies the brain lipid composition in a model of Alzheimer's disease, improving behavioral motor function and survival.

First Author  Mohaibes RJ Year  2017
Journal  Biochim Biophys Acta Volume  1859
Issue  9 Pt B Pages  1596-1603
PubMed ID  28284721 Mgi Jnum  J:255677
Mgi Id  MGI:6106242 Doi  10.1016/j.bbamem.2017.02.020
Citation  Mohaibes RJ, et al. (2017) The hydroxylated form of docosahexaenoic acid (DHA-H) modifies the brain lipid composition in a model of Alzheimer's disease, improving behavioral motor function and survival. Biochim Biophys Acta 1859(9 Pt B):1596-1603
abstractText  We have compared the effect of the commonly used omega-3 fatty acid, docosahexaenoic acid ethyl ester (DHA-EE), and of its 2-hydroxylated DHA form (DHA-H), on brain lipid composition, behavior and lifespan in a new human transgenic Drosophila melanogaster model of Alzheimer''s disease (AD). The transgenic flies expressed human Abeta42 and tau, and the overexpression of these human transgenes in the CNS of these flies produced progressive defects in motor function (antigeotaxic behavior) while reducing the animal''s lifespan. Here, we demonstrate that both DHA-EE and DHA-H increase the longer chain fatty acids (>/=18C) species in the heads of the flies, although only DHA-H produced an unknown chromatographic peak that corresponded to a non-hydroxylated lipid. In addition, only treatment with DHA-H prevented the abnormal climbing behavior and enhanced the lifespan of these transgenic flies. These benefits of DHA-H were confirmed in the well characterized transgenic PS1/APP mouse model of familial AD (5xFAD mice), mice that develop defects in spatial learning and in memory, as well as behavioral deficits. Hence, it appears that the modulation of brain lipid composition by DHA-H could have remedial effects on AD associated neurodegeneration. This article is part of a Special Issue entitled: Membrane Lipid Therapy: Drugs Targeting Biomembranes edited by Pablo V. Escriba.
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