7,10,13,16-Docosatetraenoic acid impairs neurobehavioral development by increasing reactive oxidative species production in Caenorhabditis elegans

Abstract

Aims: To investigate human breast milk (HBM) lipids that may adversely affect infant neurodevelopment.

Main methods: We performed multivariate analyses that combined lipidomics and psychologic Bayley-III scales to identify which HBM lipids are involved in regulating infant neurodevelopment. We observed a significant moderate negative correlation between 7,10,13,16-docosatetraenoic acid (omega-6, C₂₂H₃₆O₂, the common name adrenic acid, AdA) and adaptive behavioral development. We further studied the effects of AdA on neurodevelopment by using Caenorhabditis elegans (C. elegans) as a model. Worms from larval stages L1 to L4 were supplemented with AdA at 5 nominal concentrations (0 μM [control], 0.1 μM, 1 μM, 10 μM, and 100 μM) and subjected to behavioral and mechanistic analyses.

Key findings: Supplementation with AdA from larval stages L1 to L4 impaired neurobehavioral development, such as locomotive behaviors, foraging ability, chemotaxis behavior, and aggregation behavior. Furthermore, AdA upregulated the production of intracellular reactive oxygen species. AdA-induced oxidative stress blocked serotonin synthesis and serotoninergic neuron activity and inhibited expression of daf-16 and the daf-16-regulated genes mtl-1, mtl-2, sod-1, and sod-3, resulting in attenuation of the lifespan in C. elegans.

Significance: Our study reveals that AdA is a harmful HBM lipid that may have adverse effects on infant adaptive behavioral development. We believe this information may be critical for AdA administration guidance in children's health care.

Keywords: 7,10,13,16-Docosatetraenoic acid (adrenic acid); Caenorhabditis elegans; Human breast milk; Neurobehavioral development; Reactive oxidative species (ROS).