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Differential Expression of Genes Involved in Inflammatory Immune Response and Protein Ubiquitination in the Prefrontal Cortex of Rhesus Macaque with High and Low Lutein Content
Author(s) -
Mohn Emily S,
Erdman John W.,
Neuringer Martha,
Kuchan Matthew J,
Johnson Elizabeth J
Publication year - 2016
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.30.1_supplement.913.8
Subject(s) - lutein , rhesus macaque , prefrontal cortex , biology , medicine , endocrinology , immunology , neuroscience , biochemistry , cognition , carotenoid
Lutein, a carotenoid with antioxidant and anti‐inflammatory functions, accumulates in the primate brain. Studies have shown that brain levels of lutein are more consistently related to better cognitive test scores in humans than other antioxidants found in higher concentrations in the brain, such as vitamin E. Supplementation with lutein can improve verbal fluency, memory scores, and rates of learning in older adults. However, the mechanism by which lutein functions in cognition is unclear. The aim of this study was to determine the relationship between lutein concentration and gene expression profiles in rhesus macaque brain. Brain tissue was dissected from monkeys fed a chow diet containing lutein (~16 μmol/kg diet). Next generation RNA sequencing was used to determine differentially expressed genes in the prefrontal cortex of monkeys (11–13y) with high lutein content (mean=34.5 pg/mg wet weight, n=3) versus those with low lutein content (mean=11.8 pg/mg wet weight, n=3). Lutein concentrations were determined in these brain samples using HPLC. A total of 415 genes were differentially expressed between the two groups. Ingenuity Pathway Analysis (IPA) revealed the up‐regulation of pro‐inflammatory immune response pathways, such as chemokine signaling, antigen presentation, leukocyte extravasation, and neuropathic pain signaling, in brains with low lutein content. A total of 16 genes were upregulated in this pro‐inflammatory network, with specific genes of interest including beta‐2‐microglobulin and p38 MAPK (1.5 fold change for each), which are both associated with age‐related cognitive impairment and neurodegeneration. Additionally, up‐regulation of the protein ubiquitination pathway (9 genes), a hallmark of Alzheimer's disease, was observed in brains with low lutein content. These results indicate that lutein may play a role in suppressing neuroinflammation at the transcription level, and provide the first steps towards understanding the mechanisms underlying the beneficial effect of lutein on cognition. Support or Funding Information This work was supported by grants from Abbott Nutrition through the Center for Nutrition, Learning, and Memory at the University of Illinois , USDA (58‐1950‐4‐003) , and NIH grant P51OD011092 to the Oregon National Primate Research Center