Docosahexaenoic acid provides protection from impairment of learning ability in Alzheimer's disease model rats

Abstract

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-b (Ab) 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 Ab peptide-produced Alzheimer's disease model rats. After a mini-osmotic pump filled with Ab 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.

Oligomers of the amyloid-β protein disrupt working memory: Confirmation with two behavioral procedures

“…In the current study, CM from Aβ oligomer-containing 7PA2 cells significantly increased Switching and Perseveration errors under ALCR. These findings are consistent with those of Cleary et al Aβ oligomer-induced errors under ALCR have been associated with reference memory [4] and such errors in the Morris Water Maze [13] also are thought to be related to reference memory.…”

“…In view of the remarkable sensitivity of the ACLR procedure [39], however, it is not clear whether Aβ oligomers that disrupt performance under that procedure also disrupt cognitive performance in other more commonly used models of animal memory. To make this determination, the present study compared effects of natural oligomers of amyloid-β protein in separate groups of rats tested in different laboratories under an ALCR schedule and in a radial arm maze, which has been used previously with rats to demonstrate memory impairment induced by exogenous Aβ(1-40) [4,5,29] and of Aβ (25-35 [7,27,28]. In previous studies of natural oligomers of amyloid-β, only reference memory performance or performance under tasks influenced by executive function has been assessed under Aβ oligomer challenge.…”

Evidence for defective retinoid transport and function in late onset Alzheimer's disease

“…APOE regulates the transport and synthesis in neuronal membranes of docosahexaenoic acid (49), a ligand for the RXRs (50). Docosahexaenoic acid has recently been shown to protect against memory impairment in rats (51). In feedback fashion, the transcriptional expression of APOE in brain astrocytes is strongly up-regulated by RA (52).…”

Assessment of nutritional interventions for modification of age-associated cognitive decline using a canine model of human aging

“…In Alzheimer's patients, cholestryl ester-DHA levels, a biomarker for DHA, is negatively correlated with the severity of dementia (Tully et al 2003). DHA also is thought to possess antioxidant properties (Gamoh et al 2001;Hashimoto et al 2002); thus supplementation should serve to replace oxidized DHA present in phospholipids. Furthermore, DHA readily toggles between several conformations, thereby allowing the membrane phospholipids to adapt to the changes in receptor or ion channel conformations (Huber et al 2002;Koenig et al 1997).…”

“…Furthermore, DHA readily toggles between several conformations, thereby allowing the membrane phospholipids to adapt to the changes in receptor or ion channel conformations (Huber et al 2002;Koenig et al 1997). DHA also may have beneficial anti-inflammatory effects [reviewed in Horrocks and Yeo (1999)] and has been shown to have positive effects in rodent models of Alzheimer's disease (Hashimoto et al 2002;Calon et al 2004).…”