Lutein accumulates in subcellular membranes of brain regions in adult rhesus macaques: Relationship to DHA oxidation products

Abstract

ObjectivesLutein, a carotenoid with anti-oxidant functions, preferentially accumulates in primate brain and is positively related to cognition in humans. Docosahexaenoic acid (DHA), an omega-3 polyunsaturated fatty acid (PUFA), is also beneficial for cognition, but is susceptible to oxidation. The present study characterized the membrane distribution of lutein in brain regions important for different domains of cognitive function and determined whether membrane lutein was associated with brain PUFA oxidation.MethodsAdult rhesus monkeys were fed a stock diet (~2 mg/day lutein or ~0.5 μmol/kg body weight/day) (n = 9) or the stock diet plus a daily supplement of lutein (~4.5 mg/day or~1 μmol/kg body weight/day) and zeaxanthin (~0.5 mg/day or 0.1 μmol/kg body weight/day) for 6–12 months (n = 4). Nuclear, myelin, mitochondrial, and neuronal plasma membranes were isolated using a Ficoll density gradient from prefrontal cortex (PFC), cerebellum (CER), striatum (ST), and hippocampus (HC). Carotenoids, PUFAs, and PUFA oxidation products were measured using HPLC, GC, and LC-GC/MS, respectively.ResultsAll-trans-lutein (ng/mg protein) was detected in all regions and membranes and was highly variable among monkeys. Lutein/zeaxanthin supplementation significantly increased total concentrations of lutein in serum, PFC and CER, as well as lutein in mitochondrial membranes and total DHA concentrations in PFC only (P<0.05). In PFC and ST, mitochondrial lutein was inversely related to DHA oxidation products, but not those from arachidonic acid (P <0.05).DiscussionThis study provides novel data on subcellular lutein accumulation and its relationship to DHA oxidation in primate brain. These findings support the hypothesis that lutein may be associated with antioxidant functions in the brain.

The Subcellular Distribution of Alpha-Tocopherol in the Adult Primate Brain and Its Relationship with Membrane Arachidonic Acid and Its Oxidation Products

“…Rhesus monkey ( Macaca mulatta ) brains, analyzed in the present study, were from a subgroup of a larger parent study sample, which investigated the effect of lutein supplementation on lutein accumulation in brain regions and membranes of primates [ 23 ]. Our study samples included serum and brain tissue from 6 female and 3 male adult monkeys (mean age: 11.7 ± 3.3 years; mean body weight: 7.87 ± 2.24 kg) that were obtained through the Oregon National Primate Research Center (ONPRC) (Beaverton, Oregon) Tissue Distribution Program; animals were not euthanized specifically for this study, but were euthanized for other projects or for veterinary reasons.…”

“…The n-3 PUFA content was 0.13% of ration, mainly contributed by linolenic acid (0.10% of ration), but also containing DHA (~0.01% of ration). Our previous study [ 23 ] also included tissue from 4 monkeys receiving lutein supplementation, but these animals were not included in the current study, due to potential confounding effects on measures of oxidation.…”

Nutritional Gaps and Supplementation in the First 1000 Days

“…Additionally, the clarity of the lens and the short optical distance between the lens and the retina may allow significant transmission of all wavelengths of visible light into the eye [133,134]. As lutein and zeaxanthin are concentrated in the area of the retina that is most immature [135], they protect the developing retina through a number of mechanisms, namely absorption of blue wavelengths of visible light [136,137], antioxidant capacity [138,139], anti-inflammatory properties [140], and neuroprotective activity [141]. Beyond protection, they can also support transmission and processing of visual information [133,134].…”

Neural Activation During Visual Attention Differs in Individuals with High versus Low Macular Pigment Density

“…One possible mechanism is simply prophylactic: L and Z could prevent the cumulative deleterious effects of oxidative and/or inflammatory damage in the brain, as they do in the retina. Recent research investigating this hypothesis using a rhesus macaque model found associations between membrane L levels and docosahexaenoic acid oxidative byproducts in prefrontal cortex myelin and striatal myelin, as well as mitochondria in prefrontal cortex, cerebellum, and striatum, which certainly supports this hypothesis. There are a number of other antioxidants that accumulate in cortical tissues, however, so it is unlikely that even if L and Z are serving this function, they are uniquely or exclusively serving this function.…”