Differential effects of low-phenylalanine protein sources on brain neurotransmitters and behavior in C57Bl/6-Pah(enu2) mice.

[phenylketonuria]

Phenylketonuria (PKU ) is an inborn error of metabolism caused by a deficiency of the enzyme phenylalanine hydroxylase , which metabolizes phenylalanine (phe ) to tyrosine . A low -phe diet plus amino acid (AA ) formula is necessary to prevent cognitive impairment ; glycomacropeptide (GMP ) contains minimal phe and provides a palatable alternative to the AA formula . Our objective was to assess neurotransmitter concentrations in the brain and the behavioral phenotype of PKU mice (Pah (enu 2 ) on the C 5 7 Bl /6 background ) and how this is affected by low -phe protein sources . Wild type (WT ) and PKU mice , both male and female , were fed high -phe casein , low -phe AA , or low -phe GMP diets between 3 and 18 weeks of age . Behavioral phenotype was assessed using the open field and marble burying tests , and brain neurotransmitter concentrations were measured using HPLC with electrochemical detection system . Data were analyzed by 3 -way ANOVA with genotype , sex , and diet as the main treatment effects . Brain mass and the concentrations of catecholamines and serotonin were reduced in PKU mice compared to WT mice ; the low -phe AA and GMP diets improved these parameters in PKU mice . Relative brain mass was increased in female PKU mice fed the GMP diet compared to the AA diet . PKU mice exhibited hyperactivity and impaired vertical exploration compared to their WT littermates during the open field test . Regardless of genotype or diet , female mice demonstrated increased vertical activity time and increased total ambulatory and horizontal activity counts compared with male mice . PKU mice fed the high -phe casein diet buried significantly fewer marbles than WT control mice fed casein ; this was normalized in PKU mice fed the low -phe AA and GMP diets . In summary , C 5 7 Bl /6 -Pah (enu 2 ) mice showed an impaired behavioral phenotype and reduced brain neurotransmitter concentrations that were improved by the low -phe AA or GMP diets . These data support lifelong adherence to a low -phe diet for PKU .

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phenylketonuria

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