Docosahexaenoic acid reduces hypoglycemia-induced neuronal necroptosis via the peroxisome proliferator-activated receptor γ/nuclear factor-κB pathway

DHA has been shown to be neuroprotective and important to neurogenesis, but its role in HG-induced brain injury and the underlying mechanisms remain unknown. To elucidate the therapeutic effect of DHA, we established a mouse model with insulin-induced hypoglycemic brain injury and an in vitro model of HT-22 cells using a sugar-free medium. DHA treatment significantly reduced neuronal death and improved HG-induced learning and memory deficits. Moreover, DHA inhibited neuronal necroptosis and decreased the concentrations of TNF-alpha, IL-1 beta and TNFR1. DHA also activated PPAR-gamma and suppressed the NF-kappa B pathway in mouse brain tissues. In vitro, DHA treatment restored the viability and decreased necroptosis of HT-22 cells treated with glucose deprivation. However, the inhibition of PPAR-gamma with T0070907 reversed neuroprotective and anti-necroptosis effects of DHA in HG-induced brain injury, which is associated with the activation of the downstream NF-kappa B pathway. We conclude that DHA displays a protective effect against HG-induced brain injury through the PPAR-gamma/NF-kappa B pathway and represents a promising method to prevent HG-induced brain injury.

Automated summary

DHA has been shown to be neuroprotective and important to neurogenesis, playing a protective role against HG-induced brain injury through the PPAR-gamma/NF-kappa B pathway.