Docosahexaenoic acid-induced amelioration on impairment of memory learning in amyloid beta-infused rats relates to the decreases of amyloid beta and cholesterol levels in detergent-insoluble membrane fractions.
We investigated the effects of dietary administration of docosahexaenoic acid (DHA; C22:6n-3) on the levels of amyloid beta (A beta) peptide (1-40) and cholesterol in the nonionic detergent Triton 100 x-insoluble membrane fractions (DIFs) of the cerebral cortex and, also, on learning-related memory in an animal model of Alzheimer's disease (AD) rats infused with A beta peptide (1-40) into the cerebral ventricle. The infusion increased the levels of A beta peptide and cholesterol in the DIFs concurrently with a significant increase in reference memory errors (measured by eight-arm radial-maze tasks) compared with those of vehicle rats. Conversely, the dietary administration of DHA to AD-model rats decreased the levels of A beta peptide and cholesterol in the DIFs, with the decrease being more prominent in the DHA-administered rats. Regression analysis revealed a significant positive correlation between A beta peptide and each of cholesterol, palmitic acid and stearic acid, and between the number of reference memory errors and each of cholesterol, palmitic, stearic and oleic acid; moreover, a significant negative correlation was observed between the number of reference memory errors and the molar ratio of DHA to palmitic plus stearic acid. These results suggest that DHA-induced protection of memory deficits in AD-model rats is related to the interactions of cholesterol, palmitic acid or stearic acid with A beta peptides in DIFs where DHA ameliorates these interactions.
Hashimoto
Michio
M
Department of Environmental Physiology, Shimane University Faculty of Medicine, Izumo 693-8501, Japan. michio1@med.shimane-u.ac.jp
Hossain
Shahdat
S
Agdul
Haqu
H
Shido
Osamu
O
D000544:Alzheimer Disease / Q000188:drug therapy*; D016229:Amyloid beta-Peptides / Q000187:drug effects / Q000378:metabolism* / Q000494:pharmacology; D000818:Animals; D001835:Body Weight / Q000187:drug effects; D002462:Cell Membrane / Q000737:chemistry / Q000187:drug effects / Q000378:metabolism*; D002540:Cerebral Cortex / Q000187:drug effects; D002784:Cholesterol / Q000378:metabolism*; D003902:Detergents / Q000494:pharmacology; D004195:Disease Models, Animal; D004281:Docosahexaenoic Acids / Q000494:pharmacology*; D005227:Fatty Acids / Q000378:metabolism; D036502:Infusions, Intralesional; D007858:Learning / Q000187:drug effects*; D008568:Memory / Q000187:drug effects*; D017830:Octoxynol / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D012044:Regression Analysis; D012995:Solubility
D016229:Amyloid beta-Peptides; D003902:Detergents; D005227:Fatty Acids; D004281:Docosahexaenoic Acids; D017830:Octoxynol; D002784:Cholesterol