Fish oil improves learning impairments of diabetic rats by blocking PI3K/AKT/nuclear factor-κB-mediated inflammatory pathways.

Previous research has demonstrated that diabetes induces learning and memory deficits. However, the mechanism of memory impairment induced by diabetes is poorly understood. Dietary fatty acids, especially polyunsaturated fatty acids, have been shown to enhance learning and memory and prevent memory deficits in various experimental conditions. The present study investigated the effects of fish oil supplementation on the lipid peroxidation, inflammation and neuron apoptosis in the hippocampus of streptozotocin (STZ)-induced diabetes rats. The effects of diabetes and fish oil treatment on the spatial learning and memory were also evaluated using the Morris Water Maze. STZ-induced diabetes impaired spatial learning and memory of rats, which was associated with the inflammation, oxidative stress and apoptosis of hippocampal neurons. Fish oil administration ameliorated cognitive deficit, reduced oxidative stress and tumor necrosis factor α (TNF-α), protected the hippocampal neurons by increasing Protein Kinase B (AKT) phosphorylation and decreasing caspase-9 expression. These results suggested that the principle mechanisms involved in the antidiabetic and neuroprotective effect of fish oil were its antioxidant, anti-inflammatory and anti-apoptosis potential, supporting a potential role for fish oil as an adjuvant therapy for the prevention and treatment of diabetic complications.