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Blood and Brain Biochemistry and Behaviour in NTBC and Dietary Treated Tyrosinemia Type 1 Mice

Tyrosinemia type 1 (TT1) is a rare metabolic disease caused by a defect in the tyrosine degradation pathway. Neurocognitive deficiencies have been described in TT1 patients, that have, among others, been related to changes in plasma large neutral amino acids (LNAA) that could result in changes in br...

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Autores principales: van Ginkel, Willem G., van Vliet, Danique, van der Goot, Els, Faassen, Martijn H. J. R., Vogel, Arndt, Heiner-Fokkema, M. Rebecca, van der Zee, Eddy. A., van Spronsen, Francjan J.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6836052/
https://www.ncbi.nlm.nih.gov/pubmed/31623189
http://dx.doi.org/10.3390/nu11102486
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author van Ginkel, Willem G.
van Vliet, Danique
van der Goot, Els
Faassen, Martijn H. J. R.
Vogel, Arndt
Heiner-Fokkema, M. Rebecca
van der Zee, Eddy. A.
van Spronsen, Francjan J.
author_facet van Ginkel, Willem G.
van Vliet, Danique
van der Goot, Els
Faassen, Martijn H. J. R.
Vogel, Arndt
Heiner-Fokkema, M. Rebecca
van der Zee, Eddy. A.
van Spronsen, Francjan J.
author_sort van Ginkel, Willem G.
collection PubMed
description Tyrosinemia type 1 (TT1) is a rare metabolic disease caused by a defect in the tyrosine degradation pathway. Neurocognitive deficiencies have been described in TT1 patients, that have, among others, been related to changes in plasma large neutral amino acids (LNAA) that could result in changes in brain LNAA and neurotransmitter concentrations. Therefore, this project aimed to investigate plasma and brain LNAA, brain neurotransmitter concentrations and behavior in C57 Bl/6 fumarylacetoacetate hydrolase deficient (FAH−/−) mice treated with 2-(2-nitro-4-trifluoromethylbenoyl)-1,3-cyclohexanedione (NTBC) and/or diet and wild-type mice. Plasma and brain tyrosine concentrations were clearly increased in all NTBC treated animals, even with diet (p < 0.001). Plasma and brain phenylalanine concentrations tended to be lower in all FAH−/− mice. Other brain LNAA, were often slightly lower in NTBC treated FAH−/− mice. Brain neurotransmitter concentrations were usually within a normal range, although serotonin was negatively correlated with brain tyrosine concentrations (p < 0.001). No clear behavioral differences between the different groups of mice could be found. To conclude, this is the first study measuring plasma and brain biochemistry in FAH−/− mice. Clear changes in plasma and brain LNAA have been shown. Further research should be done to relate the biochemical changes to neurocognitive impairments in TT1 patients.
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spelling pubmed-68360522019-11-25 Blood and Brain Biochemistry and Behaviour in NTBC and Dietary Treated Tyrosinemia Type 1 Mice van Ginkel, Willem G. van Vliet, Danique van der Goot, Els Faassen, Martijn H. J. R. Vogel, Arndt Heiner-Fokkema, M. Rebecca van der Zee, Eddy. A. van Spronsen, Francjan J. Nutrients Article Tyrosinemia type 1 (TT1) is a rare metabolic disease caused by a defect in the tyrosine degradation pathway. Neurocognitive deficiencies have been described in TT1 patients, that have, among others, been related to changes in plasma large neutral amino acids (LNAA) that could result in changes in brain LNAA and neurotransmitter concentrations. Therefore, this project aimed to investigate plasma and brain LNAA, brain neurotransmitter concentrations and behavior in C57 Bl/6 fumarylacetoacetate hydrolase deficient (FAH−/−) mice treated with 2-(2-nitro-4-trifluoromethylbenoyl)-1,3-cyclohexanedione (NTBC) and/or diet and wild-type mice. Plasma and brain tyrosine concentrations were clearly increased in all NTBC treated animals, even with diet (p < 0.001). Plasma and brain phenylalanine concentrations tended to be lower in all FAH−/− mice. Other brain LNAA, were often slightly lower in NTBC treated FAH−/− mice. Brain neurotransmitter concentrations were usually within a normal range, although serotonin was negatively correlated with brain tyrosine concentrations (p < 0.001). No clear behavioral differences between the different groups of mice could be found. To conclude, this is the first study measuring plasma and brain biochemistry in FAH−/− mice. Clear changes in plasma and brain LNAA have been shown. Further research should be done to relate the biochemical changes to neurocognitive impairments in TT1 patients. MDPI 2019-10-16 /pmc/articles/PMC6836052/ /pubmed/31623189 http://dx.doi.org/10.3390/nu11102486 Text en © 2019 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
van Ginkel, Willem G.
van Vliet, Danique
van der Goot, Els
Faassen, Martijn H. J. R.
Vogel, Arndt
Heiner-Fokkema, M. Rebecca
van der Zee, Eddy. A.
van Spronsen, Francjan J.
Blood and Brain Biochemistry and Behaviour in NTBC and Dietary Treated Tyrosinemia Type 1 Mice
title Blood and Brain Biochemistry and Behaviour in NTBC and Dietary Treated Tyrosinemia Type 1 Mice
title_full Blood and Brain Biochemistry and Behaviour in NTBC and Dietary Treated Tyrosinemia Type 1 Mice
title_fullStr Blood and Brain Biochemistry and Behaviour in NTBC and Dietary Treated Tyrosinemia Type 1 Mice
title_full_unstemmed Blood and Brain Biochemistry and Behaviour in NTBC and Dietary Treated Tyrosinemia Type 1 Mice
title_short Blood and Brain Biochemistry and Behaviour in NTBC and Dietary Treated Tyrosinemia Type 1 Mice
title_sort blood and brain biochemistry and behaviour in ntbc and dietary treated tyrosinemia type 1 mice
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6836052/
https://www.ncbi.nlm.nih.gov/pubmed/31623189
http://dx.doi.org/10.3390/nu11102486
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