Lutein selectively accumulates in the neonatal rat brain via breast milk
Authors: Gong Xiaoming , Sambalingam Devaraj , Li Min , Ferruzzi Mario G , Rubin Lewis P 
Published: November 2023

BackgroundLutein is the principal carotenoid accumulated in primate (including human) brain throughout the lifespan. Although several epidemiological studies and clinical trials in aged individuals have pointed to a relationship between lutein status and cognitive health, mechanisms of selective lutein (and zeaxanthin) brain uptake and potential functions of lutein in early neurodevelopment and cognitive health remain poorly understood. The objective of this study is to demonstrate if a rat model of maternal and neonatal lutein supplementation can be used to interrogate maternal/fetal and milk‐to‐pup lutein uptake and brain accumulation. The model is a clinically relevant and validated simulation of human neonatal hypoxic‐ischemic (HI) brain injury.MethodsThe rat HI model consists of left carotid artery ligation on postnatal day 7 (P7) and subsequent exposure to 8% O2 for 2.5 h. In order to assess the suitability of this species for nutritional neurodevelopmental studies (here, lutein), rat dams were fed 0.25% lutein‐supplemented or control (standard) rat chow throughout pregnancy and lactation. Pups were sacrificed on P10. Gastric aspirates for ingested milk, maternal and neonatal plasma, and neonatal brain were collected and analyzed for lutein content by HPLC.ResultsMaternal dietary supplementation with lutein significantly increased lutein content in milk (~100–250 pmol/g rat milk coagulates). Maternal and neonatal lutein supplementation yielded P10 brain lutein accumulation (~12–15 pmol/g wet wt), concentrations similar in magnitude to brain lutein accumulation in other species investigated. In the absence of maternal lutein supplementation, lutein was not detectable in brain samples. When neonatal rats received dietary lutein via suckling and were additionally treated with daily i.p. injections of lutein in oil vehicle, brain lutein content was even higher than when pups received lutein only via dietary (milk) intake. In preliminary experiments, brain lutein accumulation was slightly enhanced when pups were recovering from HI brain injury. In parallel analyses, maternal lutein supplementation during gestation and lactation suppressed consequences of neonatal (P7) HI brain injury including histological injury scores, neuroinflammation, hypoxic stress pathways, and neuronal apoptosis/necrosis.ConclusionThese investigations demonstrate for the first time that at least some rodent species (here, rats) are suitable for studying maternal/fetal and neonatal dietary (milk) delivery of lutein. When dams are supplemented with dietary lutein in pregnancy and during nursing, lutein is transferred, presumably in utero, and via milk. Ingested (and injected) lutein reaches and accumulates in the developing rodent brain. This rat and, potentially, genetically manipulated mouse models, offer numerous experimental advantages for studying carotenoid effects on recovery from brain injury, other brain disorders, and behavior.Support or Funding InformationSeed grant from TTUHSC