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Title: Exploratory metabolomic analyses reveal compounds correlated with lutein concentration in frontal cortex, hippocampus, and occipital cortex of human infant brain

Author
item LIEBLEIN-BOFF, JACQUELINE - Abbott Nutrition
item JOHNSON, ELIZABETH - Jean Mayer Human Nutrition Research Center On Aging At Tufts University
item KENNEDY, ADAM - Metabolon, Inc
item LAI, CHRON-SI - Abbott Nutrition
item KUCHAN, MATTHEW - Abbott Nutrition

Submitted to: PLOS ONE
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 8/9/2015
Publication Date: 8/28/2015
Citation: Lieblein-Boff, J.C., Johnson, E.J., Kennedy, A.D., Lai, C., Kuchan, M.J. 2015. Exploratory metabolomic analyses reveal compounds correlated with lutein concentration in frontal cortex, hippocampus, and occipital cortex of human infant brain. PLoS One. 10(8):e136904. doi: 10.1371/journal.pone.0136904.

Interpretive Summary: Lutein is a dietary plant pigment (carotenoid) well known for its role in vision and recent reports suggest a role for lutein in cognition. Lutein is the major carotenoid in human brain tissue in early and late life. In addition, cognition in older adults is related to eye and brain lutein levels. Furthermore, lutein was found to selectively accumulate in infant brain compared to other carotenoids that are major in diet. How lutein functions in cognition is not clear. In an effort to understand lutein’s role in cognition, a study relating compounds involved in brain function and lutein was completed. Analyses were performed on human infant brain tissues in regions important for learning and memory. Tissues were obtained from a federally funded tissue bank. Lutein levels were related to pathways involved in brain function (involving certain fats, energy, fluid balance, neurotransmitters, and certain antioxidants). Revealing relationships between lutein and pathways may shed light on important roles of lutein in the human brain during development.

Technical Abstract: Lutein is a dietary carotenoid well known for its role as an antioxidant in the macula and recent reports implicate a role for lutein in cognitive function. Lutein is the dominant carotenoid in both pediatric and geriatric brain tissue. In addition, cognitive function in older adults correlated with macular and post-mortem brain lutein concentrations. Furthermore, lutein was found to preferentially accumulate in the infant brain in comparison to other carotenoids that are predominant in diet. While lutein is consistently related to cognitive function, the mechanisms by which lutein may influence cognition are not clear. In an effort to identify potential mechanisms through which lutein might influence neurodevelopment, an exploratory study relating metabolite signatures and lutein was completed. Post-mortem analyses were performed on human infant brain tissues in three regions important for learning and memory; the frontal cortex, hippocampus, and occipital cortex. Metabolomic profiles were compared to lutein concentration, and correlations were identified and reported here. A total of 1276 correlations were carried out across all brain regions. Of 427 metabolites analyzed, 257 were metabolites of known identity. Unidentified metabolite correlations (510) were excluded. In addition, moderated correlations with xenobiotic relationships (2) or those driven by single outliers (3) were excluded from further study. Lutein concentrations correlated with lipid pathways metabolites, energy pathway metabolites, brain osmolytes, amino acid neurotransmitters, and the antioxidant homocarnosine. These correlations were often brain region specific. Revealing relationships between lutein and metabolic pathways may help identify potential candidates on which to complete further analyses and may shed light on important roles of lutein in the human brain during development.