Docosahexanoic acid signals through the Nrf2–Nqo1 pathway to maintain redox balance and promote neurite outgrowth

We found that primary cortical neurons treated with docosohexanoic acid showed a dose-dependent increase in Nrf2 transcriptional activity and Nrf2-target gene expression

Jennifer Drolet; Brodie Buchner-Duby; Morgan G. Stykel; Carla Coackley; Jing X. Kang; David W. L. Ma; Scott D. Ryan

2021

Scholarcy highlights

  • In a healthy cell, redox imbalance is controlled by enzymes that detoxify the cell of free radicals
  • Exposure of neurons to agrochemicals triggers cellular stress events that mechanistically overlap with those evoked by mutations of the αsynuclein gene that result in familial Parkinson’s disease, including neuritic retraction, axodendritic pathology, and oxidative stress
  • We find that docosohexanoic acid increases expression of Nrf2 target genes in both Fat1 transgenic mouse brain relative to wild type and in primary rat cortical neurons treated with DHA relative to steric acid
  • Analysis of total cellular lipids composition of Fat-1 and WT brain tissue has shown that DHA is the most abundant PUFA synthesized as a result of Fat-1 transgene expression, and yields highly consistent DHA levels in brain tissue between animals
  • Quantitative PCR analysis of brain tissue isolated from WT and Fat-1 mouse brain confirmed that expression of Nrf2-transcriptional target genes was enhanced in Fat-1 animals relative to control
  • These data suggest heightened basal Nrf2 transcriptional activity in the Fat-1 brain is coincident with differentially expressed genes associated with neurite outgrowth and neuronal development, consistent with reports of enhanced neuritogenesis in Fat-1 brain
  • Gene expression analysis Microarray data from Fat-1 and wild type animals were collected previously and RAW data was downloaded and analyzed to clusters of differentially expressed genes associated with neuronal development and regulation of transcription

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