Correlations of blood and brain biochemistry in phenylketonuria: Results from the Pah-enu2 PKU mouse


Background: In phenylketonuria (PKU), treatment monitoring is based on frequent blood phenylalanine (Phe) measurements, as this is the predictor of neurocognitive and behavioural outcome by reflecting brain Phe concentrations and brain biochemical changes. Despite clinical studies describing the relevance of blood Phe to outcome in PKU patients, blood Phe does not explain the variance in neurocognitive and behavioural outcome completely. Methods: In a PKU mouse model we investigated 1) the relationship between plasma Phe and brain biochemistry (Brain Phe and monoaminergic neurotransmitter concentrations), and 2) whether blood non-Phe Large Neutral Amino Acids (LNAA) would be of additional value to blood Phe concentrations to explain brain biochemistry. To this purpose, we assessed blood amino acid concentrations and brain Phe as well as monoaminergic neurotransmitter levels in in 114 Pah-Enu2 mice on both B6 and BTBR backgrounds using (multiple) linear regression analyses. Results: Plasma Phe concentrations were strongly correlated to brain Phe concentrations, significantly negatively correlated to brain serotonin and norepinephrine concentrations and only weakly correlated to brain dopamine concentrations. From all blood markers, Phe showed the strongest correlation to brain biochemistry in PKU mice. Including non-Phe LNAA concentrations to the multiple regression model, in addition to plasma Phe, did not help explain brain biochemistry. Conclusion: This study showed that blood Phe is still the best amino acid predictor of brain biochemistry in PKU. Nevertheless, neurocognitive and behavioural outcome cannot fully be explained by blood or brain Phe concentrations, necessitating a search for other additional parameters. Take-home message: Brain biochemistry in PKU is still best explained by blood phenylalanine. Nevertheless, neurocognitive and behavioural outcome cannot fully be explained by blood or brain phenylalanine concentrations, necessitating a search for other additional parameters.

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Divisions: College of Health & Life Sciences > School of Psychology
College of Health & Life Sciences > Clinical and Systems Neuroscience
College of Health & Life Sciences > School of Optometry > Vision, Hearing and Language
College of Health & Life Sciences
Additional Information: © 2021, Elsevier. Licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International
Uncontrolled Keywords: Brain biochemistry,Large Neutral Amino Acids (LNAA),Monoaminergic neurotransmitters,Neurocognitive outcome,Phenylketonuria,Plasma amino acids,Endocrinology, Diabetes and Metabolism,Biochemistry,Molecular Biology,Genetics,Endocrinology
Publication ISSN: 1096-7206
Last Modified: 09 Apr 2024 07:26
Date Deposited: 05 Oct 2021 09:08
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Related URLs: https://linking ... 096719221007800 (Publisher URL)
http://www.scop ... tnerID=8YFLogxK (Scopus URL)
PURE Output Type: Article
Published Date: 2021-11
Published Online Date: 2021-10-02
Accepted Date: 2021-09-18
Authors: Dijkstra, Allysa M.
Van Vliet, Ninke
Van Vliet, Danique
Romani, Cristina (ORCID Profile 0000-0002-5693-4131)
Huijbregts, Stephan C.j.
Van Der Goot, Els
Hovens, Iris B.
Van Der Zee, Eddy A.
Kema, Ido P.
Heiner-fokkema, M. Rebecca
Van Spronsen, Francjan J.

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