Large neutral amino acid supplementation exerts its effect through three synergistic mechanisms: Proof of principle in phenylketonuria mice
| Autor: | Eddy A. van der Zee, Priscila Nicolao Mazzola, Pim de Blaauw, Martijn van Faassen, Ido P. Kema, Danique van Vliet, Rogier D. van Anholt, Vibeke M. Bruinenberg, Francjan J. van Spronsen, M. Rebecca Heiner-Fokkema |
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| Přispěvatelé: | Van der Zee lab, Guided Treatment in Optimal Selected Cancer Patients (GUTS), Center for Liver, Digestive and Metabolic Diseases (CLDM) |
| Jazyk: | angličtina |
| Rok vydání: | 2015 |
| Předmět: |
Male
medicine.medical_specialty Serotonin congenital hereditary and neonatal diseases and abnormalities Phenylketonurias Dopamine Neurocognitive Disorders lcsh:Medicine Phenylalanine CEREBRAL PROTEIN-SYNTHESIS DIET chemistry.chemical_compound Norepinephrine Mice Internal medicine Blood plasma Monoaminergic medicine Animals TYROSINE-HYDROXYLASE Neurotransmitter lcsh:Science Multidisciplinary GLUTAMATERGIC SYNAPTIC-TRANSMISSION BLOOD-BRAIN-BARRIER lcsh:R PHENYLALANINE Brain nutritional and metabolic diseases EARLY-TREATED PHENYLKETONURIA TRANSPORT DYSFUNCTION Disease Models Animal Endocrinology Amino Acids Neutral chemistry PKU Dietary Supplements lcsh:Q Female medicine.drug Research Article |
| Zdroj: | PLoS ONE, 10(12):e0143833. PUBLIC LIBRARY SCIENCE PLoS ONE PLoS ONE, Vol 10, Iss 12, p e0143833 (2015) |
| ISSN: | 1932-6203 |
| Popis: | Background Phenylketonuria (PKU) was the first disorder in which severe neurocognitive dysfunction could be prevented by dietary treatment. However, despite this effect, neuropsychological outcome in PKU still remains suboptimal and the phenylalanine-restricted diet is very demanding. To improve neuropsychological outcome and relieve the dietary restrictions for PKU patients, supplementation of large neutral amino acids (LNAA) is suggested as alternative treatment strategy that might correct all brain biochemical disturbances caused by high blood phenylalanine, and thereby improve neurocognitive functioning. Objective As a proof-of-principle, this study aimed to investigate all hypothesized biochemical treatment objectives of LNAA supplementation (normalizing brain phenylalanine, non-phenylalanine LNAA, and monoaminergic neurotransmitter concentrations) in PKU mice. Methods C57Bl/6 Pah-enu2 (PKU) mice and wild-type mice received a LNAA supplemented diet, an isonitrogenic/isocaloric high-protein control diet, or normal chow. After six weeks of dietary treatment, blood and brain amino acid and monoaminergic neurotransmitter concentrations were assessed. Results In PKU mice, the investigated LNAA supplementation regimen significantly reduced blood and brain phenylalanine concentrations by 33% and 26%, respectively, compared to normal chow (p |
| Databáze: | OpenAIRE |
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