LNAA supplementation in a PKU mouse model.

Vliet, D. van (Danique) (2013) LNAA supplementation in a PKU mouse model. thesis, Medicine.

Text VlietvanD.pdf Restricted to Registered users only Download (1MB)

Abstract

Phenylketonuria (PKU) is an inborn error of metabolism in which the amino acid phenylalanine (Phe) cannot be converted to tyrosine. Untreated, the markedly elevated blood Phe concentrations lead to severe mental retardation and psychiatric problems. A Phe-restricted diet prevents severe mental retardation, but outcome remains suboptimal and the diet is socially demanding. Supplementation of large neutral amino acids (LNAA) except for Phe has been suggested as a possible new treatment modality. This study investigated the effect of 6 weeks of LNAA supplementation on brain and plasma LNAA concentrations as well as brain neurotransmitter and associated metabolite concentrations in 20-26 month old PKU and wild type (WT) mice. PKU and WT mice on either high-protein diet or normal chow were used as controls. LNAA supplementation in PKU mice significantly reduced plasma Phe concentrations, while brain Phe concentrations remained unchanged. Brain non-Phe LNAA concentrations increased in PKU mice on both LNAA supplemented diet and high-protein diet, but this was only significant for tryptophan on LNAA supplemented diet. Brain serotonin and norepinephrine, but not dopamine, concentrations significantly increased on LNAA supplemented diet. The effects of LNAA supplementation in PKU mice on plasma Phe concentrations as well as on brain serotonin and norepinephrine concentrations are promising. To further develop optimal LNAA treatment for PKU patients, different LNAA treatment regimens and dosages are worth investigating.

Item Type:	Thesis (Thesis)
Supervisor name:	Spronsen, Prof. dr. F.J. van
Faculty:	Medical Sciences
Date Deposited:	25 Jun 2020 10:48
Last Modified:	25 Jun 2020 10:48
URI:	https://umcg.studenttheses.ub.rug.nl/id/eprint/959

Actions (login required)

View Item