Summary of Study ST002179
This data is available at the NIH Common Fund's National Metabolomics Data Repository (NMDR) website, the Metabolomics Workbench, https://www.metabolomicsworkbench.org, where it has been assigned Project ID PR001387. The data can be accessed directly via it's Project DOI: 10.21228/M8FB0C This work is supported by NIH grant, U2C- DK119886.
See: https://www.metabolomicsworkbench.org/about/howtocite.php
This study contains a large results data set and is not available in the mwTab file. It is only available for download via FTP as data file(s) here.
| Study ID | ST002179 |
| Study Title | Impact of nitisinone on the cerebrospinal fluid metabolome of a murine model of alkaptonuria |
| Study Summary | Background: Nitisinone induced hypertyrosinaemia is well documented in Alkaptonuria (AKU), and there is uncertainty over whether it may contribute to a decline in cognitive function and or mood by altering neurotransmitter metabolism. The aim of this work was to evaluate the impact of nitisinone on the cerebrospinal fluid (CSF) metabolome in a murine model of AKU, with a view to providing additional insight into metabolic changes that occur following treatment with nitisinone. Methods: 17 CSF samples were collected from BALB/c Hgd-/-mice (n=8, treated with nitisinone – 4 mg/L and n=9, no treatment). Samples were diluted 1:1 with deionised water and analysed using a 1290 Infinity II liquid chromatography system coupled to a 6550 quadrupole time-of-flight mass spectrometry (Agilent, Cheadle, UK). Raw data were processed using a targeted feature extraction algorithm and an established in-house accurate mass retention time database. Matched entities (±10 ppm theoretical accurate mass and ±0.3 minutes retention time window) were filtered based on their frequency and variability. Experimental groups were compared using a moderated t-test with Benjamini-Hochberg false-discovery rate adjustment. Results: Tyrosine, acetyl-tyrosine, γ-glutamyl-tyrosine, p-hydroxyphenylacetic acid and 3-(4-hydroxyphenyl)lactic acid were shown to increase in abundance (log2 fold change 2.6-6.9, 3/5 were significant p<0.05) in the mice that received nitisinone. Several other metabolites of interest were matched but no significant differences were observed, including the aromatic amino acids phenylalanine and tryptophan, and monoamine metabolites adrenaline, 3-methoxy-4-hydroxyphenylglycol and octopamine. Conclusions: Evaluation of the CSF metabolome of a murine model of AKU showed a significant difference in the abundance of a limited number of metabolites. None of these have been reported in CSF from a murine model of AKU previously. Moreover this study confirms that some monoamine metabolites do not appear to be altered following nitisinone therapy. |
| Institute | University of Liverpool Institute of Life Course & Medical Sciences |
| Last Name | Davison |
| First Name | Andrew |
| Address | 1. Department of Clinical Biochemistry and Metabolic Medicine, Liverpool Clinical Laboratories, Liverpool University Hospitals NHS Foundation Trust, Liverpool, UK; 2. Department of Musculoskeletal and Ageing Science, Institute of Life Course and Medical Sciences, University of Liverpool, Liverpool, UK 3. School of Exercise Science, Liverpool John Moores University, Liverpool, UK |
| andrew.davison@liverpoolft.nhs.uk | |
| Phone | 0151 706 4011 |
| Submit Date | 2022-05-13 |
| Num Groups | 2 |
| Total Subjects | 17 |
| Raw Data Available | Yes |
| Raw Data File Type(s) | d, mzML |
| Analysis Type Detail | LC-MS |
| Release Date | 2022-06-08 |
| Release Version | 1 |
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Project:
| Project ID: | PR001387 |
| Project DOI: | doi: 10.21228/M8FB0C |
| Project Title: | Impact of nitisinone on the cerebrospinal fluid metabolome of a murine model of alkaptonuria |
| Project Summary: | Background: Nitisinone induced hypertyrosinaemia is well documented in Alkaptonuria (AKU), and there is uncertainty over whether it may contribute to a decline in cognitive function and or mood by altering neurotransmitter metabolism. The aim of this work was to evaluate the impact of nitisinone on the cerebrospinal fluid (CSF) metabolome in a murine model of AKU, with a view to providing additional insight into metabolic changes that occur following treatment with nitisinone. Methods: 17 CSF samples were collected from BALB/c Hgd-/-mice (n=8, treated with nitisinone – 4 mg/L and n=9, no treatment). Samples were diluted 1:1 with deionised water and analysed using a 1290 Infinity II liquid chromatography system coupled to a 6550 quadrupole time-of-flight mass spectrometry (Agilent, Cheadle, UK). Raw data were processed using a targeted feature extraction algorithm and an established in-house accurate mass retention time database. Matched entities (±10 ppm theoretical accurate mass and ±0.3 minutes retention time window) were filtered based on their frequency and variability. Experimental groups were compared using a moderated t-test with Benjamini-Hochberg false-discovery rate adjustment. Results: Tyrosine, acetyl-tyrosine, γ-glutamyl-tyrosine, p-hydroxyphenylacetic acid and 3-(4-hydroxyphenyl)lactic acid were shown to increase in abundance (log2 fold change 2.6-6.9, 3/5 were significant p<0.05) in the mice that received nitisinone. Several other metabolites of interest were matched but no significant differences were observed, including the aromatic amino acids phenylalanine and tryptophan, and monoamine metabolites adrenaline, 3-methoxy-4-hydroxyphenylglycol and octopamine. Conclusions: Evaluation of the CSF metabolome of a murine model of AKU showed a significant difference in the abundance of a limited number of metabolites. None of these have been reported in CSF from a murine model of AKU previously. Moreover this study confirms that some monoamine metabolites do not appear to be altered following nitisinone therapy. |
| Institute: | University of Liverpool Institute of Life Course & Medical Sciences |
| Last Name: | Davison |
| First Name: | Andrew |
| Address: | 1. Department of Clinical Biochemistry and Metabolic Medicine, Liverpool Clinical Laboratories, Liverpool University Hospitals NHS Foundation Trust, Liverpool, UK; 2. Department of Musculoskeletal and Ageing Science, Institute of Life Course and Medical Sciences, University of Liverpool, Liverpool, UK 3. School of Exercise Science, Liverpool John Moores University, Liverpool, UK |
| Email: | andrew.davison@liverpoolft.nhs.uk |
| Phone: | 0151 706 4011 |
| Contributors: | Davison AS1,2,*, Norman BP2, Sutherland H2,3, Milan AM1,2, Jarvis JC3, Gallagher JA2, Ranganath LR1,2 |
