-3 PUFA Attenuates LPS-Induced Neuro-Injury of Neonatal Rats through the PI3K/AKT Pathway.

Inflammation may result in periventricular leukomalacia, which is the leading cause of preterm brain encephalopathy. Moreover, -3 polyunsaturated fatty acids (-3 PUFAs) play a pivotal role against central nervous system injury, which is likely related to its anti-inflammatory effect. However, the mechanism regarding the remedial effects of -3 PUFA for LPS-induced neuro-injury has remained unclear. In this study, newborn SD rats were intraperitoneally injected with LPS or < omega>-3 PUFA, and the proliferation and apoptosis of neurocytes in the hippocampus were measured by TUNEL and BrdU. Quantitative real-time PCR (qPCR) and Western blot assay were used to analyze the mRNA and protein levels of PI3K, AKT and β-catenin in vitro and in vivo. We found that -3 PUFA promoted the proliferation and migration of neurocytes in vitro and in vivo and inhibited apoptosis. Furthermore, we confirmed that -3 PUFA through the PI3K/AKT signaling pathway positively regulated the expression of PI3K and further caused the phosphorylation of AKT activation, followed by the upregulation of β-catenin expression. Interestingly, this phenomenon became more noticeable with the combined application of -3 PUFA and a PI3K/AKT agonist. In conclusion, we confirm that -3 PUFA plays an important role in neuroprotection by activating the PI3K/AKT/β-catenin pathway. It may be a promising strategy against brain injury.

Pubmed ID: 31260648