Localization of Lutein in Monkey Brain and its Potential Role in Brain Health

• Main Author: Mohn, Emily Susan
• Format: Dissertation
• Language: English
• Published: ProQuest Dissertations & Theses 01.01.2016
• Subjects: Biochemistry; Health sciences; Nutrition
• ISBN: 9781369108378; 1369108370

Lutein, a carotenoid with antioxidant and anti-inflammatory properties, selectively accumulates in primate brain and may be beneficial for cognition. The combination of lutein with docosahexaenoic acid (DHA), a long-chain n-3 polyunsaturated fatty acid (PUFA), may provide additional cognitive benefits. Lutein is known to incorporate into membranes. However, its distribution in the brain, its interactions with nutrients important for brain health (such as DHA and vitamin E), and its role in brain function remain unclear. Cognitive impairment is caused by brain cell death, which can result from impaired cell signaling, oxidative stress, and gene dysregulation. Furthermore, it is known that brain cell membranes (myelin, neuronal, mitochondrial, and nuclear) are a critical determinant of cell function and viability. Thus, maintaining structurally healthy and functional membranes is essential for cognition. The objective of this thesis was to determine the relationship between lutein and membrane composition and cell viability in regions of the brain known to control different domains of cognitive function. This objective was met through two aims using brain tissue from 11 adult rhesus monkeys (age 7–20 y) obtained from the Oregon National Primate Research Center. Nine monkeys consumed standard chow (containing 16.4 µmol/kg lutein) while two monkeys consumed the same chow plus a daily oral lutein supplement (91.16 µmol/g lutein) for 7–12 months prior to termination. This was done in order to increase the amount of lutein in the brain, thus, increasing the range of lutein concentrations across brain samples. Lutein concentrations and fatty acid profiles were determined in isolated nuclear, myelin, mitochondrial, and neuronal membranes from the striatum, cerebellum, prefrontal cortex, and hippocampus. The association of lutein and DHA levels within membranes and the subcellular deposition of vitamin E (α-tocopherol) in relation to lutein were also evaluated. Secondly, the relationship between region and membrane-specific lutein and brain cell viability was investigated. Membrane lutein concentrations, which did not preferentially accumulate in one membrane over another, were not driven by total membrane PUFA content as is the case with α-tocopherol, an antioxidant found in significantly higher concentrations in the brain. Membrane lutein accumulation was, however, related to DHA accumulation within membranes, lending support to the hypothesis that the two may function together. Lutein was inversely related to DHA in myelin and neuronal plasma membranes but positively related in mitochondrial membranes, indicating the nature of this relationship may be membrane-specific. Lutein concentrations were inversely associated with DHA oxidation more so than arachidonic acid oxidation. Furthermore, this relationship was observed in mitochondrial membranes only, whereas total α-tocopherol (not membrane-specific) was related to PUFA oxidation. Nuclear lutein content was not related to DNA damage, however, nuclear α-tocopherol concentrations were. Lutein in the neuronal plasma membrane was not related to ERK activation, while PUFA concentrations in this membrane were positively associated with activation of this pathway. Although no cause-and-effect conclusions can be drawn from this thesis, the collective findings suggest that lutein may act as an antioxidant in the brain but its role may be related to functions other than that of a free radical scavenger. Results from this thesis provide a critical first step toward understanding how lutein functions in the brain and have generated hypotheses for future studies investigating the mechanism underlying the beneficial effect of lutein on cognition.