Docosahexaenoic acid-induced protective effect against impaired learning in amyloid beta-infused rats is associated with increased synaptosomal membrane fluidity.
In the present study, we investigated the relationship between the docosahexaenoic acid (DHA)-induced protection of learning deficit of amyloid beta(1-40)-infused Alzheimer's disease (AD) model rats and changes in synaptosomal plasma membrane fluidity of the cerebral cortex. Synaptosomal membrane lateral and rotational fluidity were measured using pyrene excimer spectroscopy and fluorescence polarization of 1,6-diphenyl-1,3,5-hexatriene (DPH), respectively. Avoidance learning ability, as assessed by a two-way active avoidance paradigm, decreased significantly in the AD model rats. Pyrene-determined annular/non-annular fluidity ratio and the DPH-determined bulk fluidity of the synaptosomal plasma membrane decreased in the amyloid beta(1-40)-infused rats. Oral pre-administration of DHA (300 mg/kg per day for 12 weeks) significantly increased both lateral and rotational fluidity. The synaptosomal membrane DHA content increased and the cholesterol to phospholipid molar ratio and lipid peroxidation decreased. The annular to non-annular fluidity ratio of the synaptic plasma membrane was positively correlated with total avoidance learning. The present results indicate that DHA-induced alterations in synaptic plasma membrane fluidity may contribute to the synaptic plasma membrane-related functions that constitute avoidance learning-related memory in amyloid beta(1-40)-infused rats.
Hashimoto
Michio
M
Department of Environmental Physiology, Shimane University, Faculty of Medicine, Izumo, Japan. michio1@med.shimane-u.ac.jp
Hossain
Shahdat
S
Shimada
Toshio
T
Shido
Osamu
O
D000544:Alzheimer Disease / Q000139:chemically induced* / Q000188:drug therapy; D016229:Amyloid beta-Peptides; D000818:Animals; D001362:Avoidance Learning / Q000187:drug effects; D004281:Docosahexaenoic Acids / Q000494:pharmacology* / Q000627:therapeutic use; D007858:Learning / Q000187:drug effects*; D007859:Learning Disabilities / Q000139:chemically induced / Q000517:prevention & control*; D008051:Lipid Bilayers / Q000737:chemistry; D015227:Lipid Peroxidation / Q000187:drug effects; D008297:Male; D008560:Membrane Fluidity / Q000187:drug effects*; D008563:Membrane Lipids / Q000032:analysis; D008954:Models, Biological; D008962:Models, Theoretical; D010446:Peptide Fragments; D051381:Rats; D017208:Rats, Wistar; D013570:Synaptic Membranes / Q000187:drug effects*
D016229:Amyloid beta-Peptides; D008051:Lipid Bilayers; D008563:Membrane Lipids; D010446:Peptide Fragments; C078592:amyloid beta-protein (1-40); D004281:Docosahexaenoic Acids