Effect of docosahexaenoic acid on hippocampal neurons in high-glucose condition: Involvement of PI3K/AKT/nuclear factor-κB-mediated inflammatory pathways

• High glucose increases the lipid peroxidation of the cultured hippocampal neurons.
• High glucose promotes the IKKβ/NF-κB activation and inflammatory level in neurons.
• High glucose impairs insulin signaling by suppressing PI3K/AKT activities.
• Docosahexaenoic acid prevents the neuron apoptosis induced by high glucose.

Accumulating evidence suggested that hyperglycemia played a critical role in hippocampus dysfunction in patients with diabetes mellitus. However, the multifactorial pathogenesis of hyperglycemia-induced impairments of hippocampal neurons has not been fully elucidated. Docosahexaenoic acid (DHA) has been shown to enhance learning and memory and affect neural function in various experimental conditions. The present study investigated the effects of DHA on the lipid peroxidation, the level of inflammatory cytokines and neuron apoptosis in the hippocampal neurons in high-glucose condition. High-glucose administration increased the level of tumor necrosis factor α (TNF-α) and IL-6, induced oxidative stress and apoptosis of hippocampal neurons in vitro. DHA treatment reduced oxidative stress and TNF-α expression, protected the hippocampal neurons by increasing AKT phosphorylation and decreasing caspase-3 and caspase-9 expression. These results suggested that high-glucose exposure induced injury of hippocampal neurons in vitro, and the principle mechanisms involved in the neuroprotective effect of DHA were its antioxidant and anti-apoptotic potential. DHA may thus be of use in preventing or treating neuron-degeneration resulting from hyperglycemia.