Use of Dietary Supplementation of Unsaturated Fatty Acids to Delay Onset of Learning and Memory Deficits in TgCRND8 Mice

Abstract

Alzheimer’s disease (AD) is a complex neurodegenerative disorder, involving metabolic dysfunction, pathogenic aggregation of amyloid beta, and deteriorating cognitive function. Patients exhibit deficiency in omega-3,-6,-9 unsaturated fatty acids (UFAs) in plasma and brain membrane phospholipids, suggesting aberrant fatty acid metabolism influences pathology. Cognitive benefits of omega UFAs in AD remain unknown. Here, I examined effects of a four-month dietary supplementation with UFAs for capacity to alter learning and memory behaviour in an AD mouse model. Cognitive impairment in a fifth generation backcross (N5) C57BL/6Crl X C3H/HeJ TgCRND8 (Tg) mice was compared to control (NonTg) littermates, with respect to both males and females, at six months of age using the Morris Water Maze (MWM). Impairment differed between sexes; female Tg mice were severely impaired, whereas male Tg mice displayed delayed learning. A reduced visual acuity in Tg and NonTg mice, shown by adapted SLAG reflex test, did not impair spatial navigation in cued MWM. A four-month omega-6/-9 UFA oral treatment (75 mg/kg/day) improved learning and memory of Tg mice as compared to vehicle and untreated controls. Omega-3 UFAs, or vehicle alone, did not alter learning and memory of Tg and NonTg mice. Thus, dietary supplementation, particularly when enriched in omega-6/9 UFAs, can affect neural function, and delay conversion from a presymptomatic to symptomatic state in the TgCRND8 mouse model.