Summary of Study ST002442
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 PR001573. The data can be accessed directly via it's Project DOI: 10.21228/M8CD9V 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 | ST002442 |
| Study Title | Alterations in CSF Urea Occur in Late Manifest Stage Huntington Disease |
| Study Type | untargeted metabolomics analysis |
| Study Summary | Huntington Disease (HD) is a neurodegenerative disorder caused by expanded cytosine-adenine-guanine (CAG) repeats in the Huntingtin gene, resulting in the production of mutant huntingtin proteins (mHTT). Previous research has identified urea as a key metabolite elevated in HD animal models and post-mortem tissues of HD patients. The exact timing of these elevations in urea and the molecular mechanism(s) responsible for these disturbances remain unknown. To better understand the pathophysiologic mechanisms responsible for elevations in urea in HD, we completed a global metabolomic profile of cerebrospinal fluid (CSF) from individuals who were at several stages of disease: pre-manifest (PRE), manifest (MAN), and late-manifest (LATE) HD participants compared to controls. We found approximately 500 metabolites were significantly altered in pre-manifest participants compared to controls, although no significant difference in CSF urea or urea metabolites. Interestingly, CSF urea was only significantly elevated in LATE participants compared to controls. There were no changes in the urea metabolites, citrulline, ornithine and arginine throughout disease; however, we did observe changes in acetate, creatinine, 4-acetamidobutanoate and 4-aminobutyraldehyde which are indirect modifiers of urea. Overall, our study confirms that elevations in urea do occur in HD, albeit later in disease and that these changes may reflect more central impairments to cellular energy metabolism yet to be explored. |
| Institute | Vanderbilt University |
| Department | Chemistry |
| Laboratory | Center for Innovative Technology |
| Last Name | CODREANU |
| First Name | SIMONA |
| Address | 1234 STEVENSON CENTER LANE |
| SIMONA.CODREANU@VANDERBILT.EDU | |
| Phone | 6158758422 |
| Submit Date | 2023-01-12 |
| Num Groups | 4 |
| Total Subjects | 60 |
| Raw Data Available | Yes |
| Raw Data File Type(s) | raw(Thermo) |
| Analysis Type Detail | LC-MS |
| Release Date | 2023-01-25 |
| Release Version | 1 |
Select appropriate tab below to view additional metadata details:
Combined analysis:
| Analysis ID | AN003979 |
|---|---|
| Analysis type | MS |
| Chromatography type | HILIC |
| Chromatography system | Thermo Vanquish |
| Column | Waters ACQUITY UPLC BEH HILIC (100 x 2.1mm,1.7um) |
| MS Type | ESI |
| MS instrument type | Orbitrap |
| MS instrument name | Thermo Q Exactive HF hybrid Orbitrap |
| Ion Mode | POSITIVE |
| Units | time_m/z |
Chromatography:
| Chromatography ID: | CH002942 |
| Chromatography Summary: | CSF extracts (5uL injection volume) were separated on an ACQUITY UPLC BEH Amide HILIC 1.7μm, 2.1 × 100 mm column (Waters Corporation, Milford, MA) held at 30°C as previously described (cite). Briefly, liquid chromatography was performed at 200 µL min−1 using solvent A (5 mM ammonium formate in 90% water, 10% acetonitrile and 0.1% formic acid) and solvent B (5 mM ammonium formate in 90% acetonitrile, 10% water and 0.1% formic acid) with a gradient length of 30 min. |
| Methods Filename: | Metabolomics_Analyses.pdf |
| Instrument Name: | Thermo Vanquish |
| Column Name: | Waters ACQUITY UPLC BEH HILIC (100 x 2.1mm,1.7um) |
| Column Temperature: | 30 |
| Flow Gradient: | 30 min |
| Flow Rate: | 0.20mL/min |
| Solvent A: | 90% water, 10% acetonitrile, 5mM Ammonium Formate, 0.1%FA |
| Solvent B: | 10% water, 90% acetonitrile, 5mM Ammonium Formate, 0.1%FA |
| Chromatography Type: | HILIC |
