Publication

Long-term dietary intervention with low Phe and/or a specific nutrient combination improve certain aspects of brain functioning in phenylketonuria (PKU)

Bruinenberg, V. M., van Vliet, D., van der Goot, E., Counotte, D. S., Kuhn, M., van Spronsen, F. J. & van der Zee, E. A., 15-Mar-2019, In : PLoS ONE. 14, 3, 20 p., 0213391.

Research output: Contribution to journalArticleAcademicpeer-review

APA

Bruinenberg, V. M., van Vliet, D., van der Goot, E., Counotte, D. S., Kuhn, M., van Spronsen, F. J., & van der Zee, E. A. (2019). Long-term dietary intervention with low Phe and/or a specific nutrient combination improve certain aspects of brain functioning in phenylketonuria (PKU). PLoS ONE, 14(3), [0213391]. https://doi.org/10.1371/journal.pone.0213391

Author

Bruinenberg, Vibeke M. ; van Vliet, Danique ; van der Goot, Els ; Counotte, Danielle S. ; Kuhn, Mirjam ; van Spronsen, Francjan J. ; van der Zee, Eddy A. / Long-term dietary intervention with low Phe and/or a specific nutrient combination improve certain aspects of brain functioning in phenylketonuria (PKU). In: PLoS ONE. 2019 ; Vol. 14, No. 3.

Harvard

Bruinenberg, VM, van Vliet, D, van der Goot, E, Counotte, DS, Kuhn, M, van Spronsen, FJ & van der Zee, EA 2019, 'Long-term dietary intervention with low Phe and/or a specific nutrient combination improve certain aspects of brain functioning in phenylketonuria (PKU)', PLoS ONE, vol. 14, no. 3, 0213391. https://doi.org/10.1371/journal.pone.0213391

Standard

Long-term dietary intervention with low Phe and/or a specific nutrient combination improve certain aspects of brain functioning in phenylketonuria (PKU). / Bruinenberg, Vibeke M.; van Vliet, Danique; van der Goot, Els; Counotte, Danielle S.; Kuhn, Mirjam; van Spronsen, Francjan J.; van der Zee, Eddy A.

In: PLoS ONE, Vol. 14, No. 3, 0213391, 15.03.2019.

Research output: Contribution to journalArticleAcademicpeer-review

Vancouver

Bruinenberg VM, van Vliet D, van der Goot E, Counotte DS, Kuhn M, van Spronsen FJ et al. Long-term dietary intervention with low Phe and/or a specific nutrient combination improve certain aspects of brain functioning in phenylketonuria (PKU). PLoS ONE. 2019 Mar 15;14(3). 0213391. https://doi.org/10.1371/journal.pone.0213391


BibTeX

@article{6f42755d43f4440ca47400c71b8c33c9,
title = "Long-term dietary intervention with low Phe and/or a specific nutrient combination improve certain aspects of brain functioning in phenylketonuria (PKU)",
abstract = "IntroductionIn phenylketonuria (PKU), a gene mutation in the phenylalanine metabolic pathway causes accumulation of phenylalanine (Phe) in blood and brain. Although early introduction of a Phe-restricted diet can prevent severe symptoms from developing, patients who are diagnosed and treated early still experience deficits in cognitive functioning indicating shortcomings of current treatment. In the search for new and/or additional treatment strategies, a specific nutrient combination (SNC) was postulated to improve brain function in PKU. In this study, a long-term dietary intervention with a low-Phe diet, a specific combination of nutrients designed to improve brain function, or both concepts together was investigated in male and female BTBR PKU and WT mice.Material & methods48 homozygous wild-types (WT, +/+) and 96 PKU BTBRPah2 (-/-) male and female mice received dietary interventions from postnatal day 31 till 10 months of age and were distributed in the following six groups: high Phe diet (WT C-HP, PKU C-HP), high Phe plus specific nutrient combination (WT SNC-HP, PKU SNC-HP), PKU low-Phe diet (PKU C-LP), and PKU low-Phe diet plus specific nutrient combination (PKU SNC- LP). Memory and motor function were tested at time points 3, 6, and 9 months after treatment initiation in the open field (OF), novel object recognition test (NOR), spatial object recognition test (SOR), and the balance beam (BB). At the end of the experiments, brain neurotransmitter concentrations were determined.ResultsIn the NOR, we found that PKU mice, despite being subjected to high Phe conditions, could master the task on all three time points when supplemented with SNC. Under low Phe conditions, PKU mice on control diet could master the NOR at all three time points, while PKU mice on the SNC supplemented diet could master the task at time points 6 and 9 months. SNC supplementation did not consistently influence the performance in the OF, SOR or BB in PKU mice. The low Phe diet was able to normalize concentrations of norepinephrine and serotonin; however, these neurotransmitters were not influenced by SNC supplementation.ConclusionThis study demonstrates that both a long-lasting low Phe diet, the diet enriched with SNC, as well as the combined diet was able to ameliorate some, but not all of these PKU-induced abnormalities. Specifically, this study is the first long-term intervention study in BTBR PKU mice that shows that SNC supplementation can specifically improve novel object recognition.",
keywords = "MEMORY, DYSFUNCTION, OUTCOMES, DECLINE, ADULTS, MICE",
author = "Bruinenberg, {Vibeke M.} and {van Vliet}, Danique and {van der Goot}, Els and Counotte, {Danielle S.} and Mirjam Kuhn and {van Spronsen}, {Francjan J.} and {van der Zee}, {Eddy A.}",
year = "2019",
month = "3",
day = "15",
doi = "10.1371/journal.pone.0213391",
language = "English",
volume = "14",
journal = "PLOS-One",
issn = "1932-6203",
publisher = "PUBLIC LIBRARY SCIENCE",
number = "3",

}

RIS

TY - JOUR

T1 - Long-term dietary intervention with low Phe and/or a specific nutrient combination improve certain aspects of brain functioning in phenylketonuria (PKU)

AU - Bruinenberg, Vibeke M.

AU - van Vliet, Danique

AU - van der Goot, Els

AU - Counotte, Danielle S.

AU - Kuhn, Mirjam

AU - van Spronsen, Francjan J.

AU - van der Zee, Eddy A.

PY - 2019/3/15

Y1 - 2019/3/15

N2 - IntroductionIn phenylketonuria (PKU), a gene mutation in the phenylalanine metabolic pathway causes accumulation of phenylalanine (Phe) in blood and brain. Although early introduction of a Phe-restricted diet can prevent severe symptoms from developing, patients who are diagnosed and treated early still experience deficits in cognitive functioning indicating shortcomings of current treatment. In the search for new and/or additional treatment strategies, a specific nutrient combination (SNC) was postulated to improve brain function in PKU. In this study, a long-term dietary intervention with a low-Phe diet, a specific combination of nutrients designed to improve brain function, or both concepts together was investigated in male and female BTBR PKU and WT mice.Material & methods48 homozygous wild-types (WT, +/+) and 96 PKU BTBRPah2 (-/-) male and female mice received dietary interventions from postnatal day 31 till 10 months of age and were distributed in the following six groups: high Phe diet (WT C-HP, PKU C-HP), high Phe plus specific nutrient combination (WT SNC-HP, PKU SNC-HP), PKU low-Phe diet (PKU C-LP), and PKU low-Phe diet plus specific nutrient combination (PKU SNC- LP). Memory and motor function were tested at time points 3, 6, and 9 months after treatment initiation in the open field (OF), novel object recognition test (NOR), spatial object recognition test (SOR), and the balance beam (BB). At the end of the experiments, brain neurotransmitter concentrations were determined.ResultsIn the NOR, we found that PKU mice, despite being subjected to high Phe conditions, could master the task on all three time points when supplemented with SNC. Under low Phe conditions, PKU mice on control diet could master the NOR at all three time points, while PKU mice on the SNC supplemented diet could master the task at time points 6 and 9 months. SNC supplementation did not consistently influence the performance in the OF, SOR or BB in PKU mice. The low Phe diet was able to normalize concentrations of norepinephrine and serotonin; however, these neurotransmitters were not influenced by SNC supplementation.ConclusionThis study demonstrates that both a long-lasting low Phe diet, the diet enriched with SNC, as well as the combined diet was able to ameliorate some, but not all of these PKU-induced abnormalities. Specifically, this study is the first long-term intervention study in BTBR PKU mice that shows that SNC supplementation can specifically improve novel object recognition.

AB - IntroductionIn phenylketonuria (PKU), a gene mutation in the phenylalanine metabolic pathway causes accumulation of phenylalanine (Phe) in blood and brain. Although early introduction of a Phe-restricted diet can prevent severe symptoms from developing, patients who are diagnosed and treated early still experience deficits in cognitive functioning indicating shortcomings of current treatment. In the search for new and/or additional treatment strategies, a specific nutrient combination (SNC) was postulated to improve brain function in PKU. In this study, a long-term dietary intervention with a low-Phe diet, a specific combination of nutrients designed to improve brain function, or both concepts together was investigated in male and female BTBR PKU and WT mice.Material & methods48 homozygous wild-types (WT, +/+) and 96 PKU BTBRPah2 (-/-) male and female mice received dietary interventions from postnatal day 31 till 10 months of age and were distributed in the following six groups: high Phe diet (WT C-HP, PKU C-HP), high Phe plus specific nutrient combination (WT SNC-HP, PKU SNC-HP), PKU low-Phe diet (PKU C-LP), and PKU low-Phe diet plus specific nutrient combination (PKU SNC- LP). Memory and motor function were tested at time points 3, 6, and 9 months after treatment initiation in the open field (OF), novel object recognition test (NOR), spatial object recognition test (SOR), and the balance beam (BB). At the end of the experiments, brain neurotransmitter concentrations were determined.ResultsIn the NOR, we found that PKU mice, despite being subjected to high Phe conditions, could master the task on all three time points when supplemented with SNC. Under low Phe conditions, PKU mice on control diet could master the NOR at all three time points, while PKU mice on the SNC supplemented diet could master the task at time points 6 and 9 months. SNC supplementation did not consistently influence the performance in the OF, SOR or BB in PKU mice. The low Phe diet was able to normalize concentrations of norepinephrine and serotonin; however, these neurotransmitters were not influenced by SNC supplementation.ConclusionThis study demonstrates that both a long-lasting low Phe diet, the diet enriched with SNC, as well as the combined diet was able to ameliorate some, but not all of these PKU-induced abnormalities. Specifically, this study is the first long-term intervention study in BTBR PKU mice that shows that SNC supplementation can specifically improve novel object recognition.

KW - MEMORY

KW - DYSFUNCTION

KW - OUTCOMES

KW - DECLINE

KW - ADULTS

KW - MICE

U2 - 10.1371/journal.pone.0213391

DO - 10.1371/journal.pone.0213391

M3 - Article

VL - 14

JO - PLOS-One

JF - PLOS-One

SN - 1932-6203

IS - 3

M1 - 0213391

ER -

ID: 80568507