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

TLDR

Docosahexaenoic acid (DHA) is a major brain n‑3 fatty acid linked to memory restoration and enhancement. The study examined whether dietary DHA pre‑administration could protect avoidance learning in a rat model of Alzheimer’s disease induced by intracerebroventricular amyloid‑β (Aβ) peptide. Rats received Aβ or vehicle via a mini‑osmotic pump and were then tested in an active shuttle‑avoidance task. DHA pre‑administration preserved avoidance learning, raised the cortico‑hippocampal DHA/arachidonic acid ratio, reduced neuronal apoptosis, increased glutathione and glutathione‑reductase activity, and lowered lipid peroxides and reactive oxygen species, suggesting enhanced antioxidant defense and a potential prophylactic strategy against Alzheimer’s‑related learning deficits.

Abstract

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‐β (Aβ) 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 Aβ peptide‐produced Alzheimer's disease model rats. After a mini‐osmotic pump filled with Aβ 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.