Docosahexaenoic acid provides protection from impairment of learning ability in Alzheimer's disease model rats.
Docosahexaenoic acid (C22:6, n-3), a major n-3 fatty acid of the brain, has been implicated in restoration and enhancement of memory-related functions. Because Alzheimer's disease impairs memory, and infusion of amyloid-beta (Abeta) peptide (1-40) into the rat cerebral ventricle reduces learning ability, we investigated the effect of dietary pre-administration of docosahexaenoic acid on avoidance learning ability in Abeta peptide-produced Alzheimer's disease model rats. After a mini-osmotic pump filled with Abeta peptide or vehicle was implanted in docosahexaenoic acid-fed and control rats, they were subjected to an active avoidance task in a shuttle avoidance system apparatus. Pre-administration of docosahexaenoic acid had a profoundly beneficial effect on the decline in avoidance learning ability in the Alzheimer's disease model rats, associated with an increase in the cortico-hippocampal docosahexaenoic acid/arachidonic acid molar ratio, and a decrease in neuronal apoptotic products. Docosahexaenoic acid pre-administration furthermore increased cortico-hippocampal reduced glutathione levels and glutathione reductase activity, and suppressed the increase in lipid peroxide and reactive oxygen species levels in the cerebral cortex and hippocampus of the Alzheimer's disease model rats, suggesting an increase in antioxidative defence. Docosahexaenoic acid is thus a possible prophylactic means for preventing the learning deficiencies of Alzheimer's disease.
Hashimoto
Michio
M
Department of Physiology, Shimane Medical University, Izumo, Japan. michio1@shimane-med.ac.jp
Hossain
Shahdat
S
Shimada
Toshio
T
Sugioka
Kozo
K
Yamasaki
Hiroshi
H
Fujii
Yoshimi
Y
Ishibashi
Yutaka
Y
Oka
Jun-Ichiro
J
Shido
Osamu
O
D000284:Administration, Oral; D000544:Alzheimer Disease / Q000139:chemically induced / Q000517:prevention & control*; D016229:Amyloid beta-Peptides; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D016718:Arachidonic Acid / Q000032:analysis; D001362:Avoidance Learning / Q000187:drug effects*; D001522:Behavior, Animal / Q000187:drug effects; D001835:Body Weight / Q000187:drug effects; D002540:Cerebral Cortex / Q000737:chemistry / Q000187:drug effects; D004032:Diet; D004195:Disease Models, Animal; D004281:Docosahexaenoic Acids / Q000008:administration & dosage / Q000032:analysis / Q000494:pharmacology*; D004353:Drug Evaluation, Preclinical; D006624:Hippocampus / Q000737:chemistry / Q000187:drug effects; D007276:Injections, Intraventricular; D008297:Male; D009474:Neurons / Q000187:drug effects; D018696:Neuroprotective Agents / Q000008:administration & dosage / Q000032:analysis / Q000494:pharmacology; D010084:Oxidation-Reduction / Q000187:drug effects; D010446:Peptide Fragments; D051381:Rats; D017208:Rats, Wistar; D017382:Reactive Oxygen Species / Q000032:analysis; D016896:Treatment Outcome
D016229:Amyloid beta-Peptides; D018696:Neuroprotective Agents; D010446:Peptide Fragments; D017382:Reactive Oxygen Species; C078592:amyloid beta-protein (1-40); D004281:Docosahexaenoic Acids; D016718:Arachidonic Acid