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

Abstract

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-α, IL-1β and TNFR1. DHA also activated PPAR-γ and suppressed the NF-κB 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-γ 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-κB pathway. We conclude that DHA displays a protective effect against HG-induced brain injury through the PPAR-γ/NF-κB pathway and represents a promising method to prevent HG-induced brain injury.

• Authors: Lin Huang, Yue Zhou, Zhi-Xian Gou, Feng Zhang, Li-Qun Lu
• Journal: Brain research (Brain Res) Vol. 1774 Pg. 147708 (01 01 2022) ISSN: 1872-6240 [Electronic] Netherlands
• PMID: 34785255 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2021. Published by Elsevier B.V.

Chemical References

• Interleukin-1beta
• NF-kappa B
• PPAR gamma
• Receptors, Tumor Necrosis Factor, Type I
• Tumor Necrosis Factor-alpha
• Docosahexaenoic Acids
• Insulin Glargine

Topics

• Animals
• Cell Line
• Docosahexaenoic Acids (pharmacology)
• Hypoglycemia (chemically induced, metabolism)
• Insulin Glargine
• Interleukin-1beta (metabolism)
• Mice
• NF-kappa B (metabolism)
• Necroptosis (drug effects)
• Neurons (drug effects, metabolism)
• PPAR gamma (metabolism)
• Receptors, Tumor Necrosis Factor, Type I (metabolism)
• Signal Transduction (drug effects)
• Tumor Necrosis Factor-alpha (metabolism)