Summary of Study ST001281
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 PR000866. The data can be accessed directly via it's Project DOI: 10.21228/M8R963 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 | ST001281 |
| Study Title | Transgenic Parkinson's Mice Following Immunotherapy |
| Study Summary | An UHPLC-HRMS Metabolomics and Lipidomics Study of Stool from Transgenic Parkinson's disease Mice Following Immunotherapy. Parkinson’s disease (PD) is characterized by the loss of dopaminergic neurons in the substantia nigra pars compacta of the brain as well as degeneration of motor and non-motor circuitry. The cause of neuronal death is currently unknown, although chronic neuroinflammation, aggregated α-synuclein, mitochondrial dysfunction and oxidative stress have all been implicated. Gliosis has been shown to exacerbate neuroinflammation via secretion of pro-inflammatory cytokines, and there is a subsequent infiltration of T lymphocytes (T-cells), into the brain of PD patients. Using liquid chromatography-high resolution mass spectrometry (LC-HRMS), we have observed metabolomic changes in stool samples, thought to be associated with the potential disease-modifying effect of an immunotherapy administered to transgenic Parkinsonian (A53T) mice. Significant elevations (p<0.05) in metabolites associated with immune response (taurine, histamine and its methylated product, 3-methylhistamine) are identified as being higher in the mice undergoing immunotherapy. Furthermore, a reduction in triacylglycerols (TG) and diacylglyceols (DG) expression in stool following immunotherapy suggests a regulation of lipid breakdown or biosynthesis with the vaccine. These “omics” markers (among others reported in this article) along with weight gain and increased life expectancy suggest that the immunotherapy is positively modifying the disease state. |
| Institute | University of Florida |
| Department | CHEMISTRY |
| Last Name | Gill |
| First Name | Emily |
| Address | BUCKMAN DRIVE, GAINESVILLE,FL ,32611, USA |
| emilygill2014@ufl.edu | |
| Phone | (352) 222-9749 |
| Submit Date | 2019-10-23 |
| Raw Data Available | Yes |
| Raw Data File Type(s) | raw(Thermo) |
| Analysis Type Detail | LC-MS |
| Release Date | 2020-01-13 |
| Release Version | 1 |
Select appropriate tab below to view additional metadata details:
Project:
| Project ID: | PR000866 |
| Project DOI: | doi: 10.21228/M8R963 |
| Project Title: | Transgenic Parkinson's Mice Following Immunotherapy |
| Project Summary: | An UHPLC-HRMS Metabolomics and Lipidomics Study of Stool from Transgenic Parkinson's disease Mice Following Immunotherapy. Parkinson’s disease (PD) is characterized by the loss of dopaminergic neurons in the substantia nigra pars compacta of the brain as well as degeneration of motor and non-motor circuitry. The cause of neuronal death is currently unknown, although chronic neuroinflammation, aggregated α-synuclein, mitochondrial dysfunction and oxidative stress have all been implicated. Gliosis has been shown to exacerbate neuroinflammation via secretion of pro-inflammatory cytokines, and there is a subsequent infiltration of T lymphocytes (T-cells), into the brain of PD patients. Using liquid chromatography-high resolution mass spectrometry (LC-HRMS), we have observed metabolomic changes in stool samples, thought to be associated with the potential disease-modifying effect of an immunotherapy administered to transgenic Parkinsonian (A53T) mice. Significant elevations (p<0.05) in metabolites associated with immune response (taurine, histamine and its methylated product, 3-methylhistamine) are identified as being higher in the mice undergoing immunotherapy. Furthermore, a reduction in triacylglycerols (TG) and diacylglyceols (DG) expression in stool following immunotherapy suggests a regulation of lipid breakdown or biosynthesis with the vaccine. These “omics” markers (among others reported in this article) along with weight gain and increased life expectancy suggest that the immunotherapy is positively modifying the disease state. |
| Institute: | University of Florida |
| Department: | CHEMISTRY |
| Last Name: | Gill |
| First Name: | Emily |
| Address: | BUCKMAN DRIVE, GAINESVILLE, FL, 32611, USA |
| Email: | emilygill2014@ufl.edu |
| Phone: | (352) 222-9749 |
| Funding Source: | Southeast Center for Intergrated Metabolomics |
| Publications: | J Proteome Res, 2019. |
| Contributors: | Emily L. Gill, Jeremy P. Koelmel, Laurel Meke, Richard A. Yost, Timothy J. Garrett, Michael S. Okun, Catherine Flores, and Vinata Vedam-Mai |
Subject:
| Subject ID: | SU001353 |
| Subject Type: | Mammal |
| Subject Species: | Mus musculus |
| Taxonomy ID: | 10090 |
Factors:
Subject type: Mammal; Subject species: Mus musculus (Factor headings shown in green)
| mb_sample_id | local_sample_id | Treatment |
|---|---|---|
| SA093490 | Blank | Blank |
| SA093491 | Tg1 | Control |
| SA093492 | Tg3 | Control |
| SA093493 | Tg2 | Control |
| SA093494 | T1 | Vaccinated |
| SA093495 | T2 | Vaccinated |
| SA093496 | T3 | Vaccinated |
| Showing results 1 to 7 of 7 |
Collection:
| Collection ID: | CO001347 |
| Collection Summary: | Stool samples were collected at 12 months, while the mice were under clinical observation. Stool was the chosen sample of analysis because of its ease of collection. |
| Sample Type: | Feces |
| Storage Conditions: | -80℃ |
Treatment:
| Treatment ID: | TR001368 |
| Treatment Summary: | All animal procedures were approved by UF IACUC, at the University of Florida. Animals were housed in a 12h light-12h dark schedule, and were provided with a diet of Envigo Mouse Chow (Huntingdon, England) and water ad libitum. Animals were housed in groups, including 3 PD and 3 vaccinated PD mice. Female, age-matched heterozygous M83 mice were used in all experiments. The immunotherapy was administered at 6 months, prior to the development of any overt physical symptoms of PD. Briefly, dendritic cells (DC) were pulsed with α-syn (A53T) RNA to generate DC vaccine, and A53T α-syn-specific T cells were generated ex vivo for adoptive transfer into M83 mice expressing the α-syn mutation. A53T α-syn-specific T cells were adoptively transferred intravenously after 5-7d of co-culture via a single injection of 107 autologous ex vivo–expanded T cells. |
Sample Preparation:
| Sampleprep ID: | SP001361 |
| Sampleprep Summary: | Folch extraction for lipidomics and protein precipitation for metabolomics. |
Combined analysis:
| Analysis ID | AN002122 | AN002123 | AN002124 | AN002125 |
|---|---|---|---|---|
| Analysis type | MS | MS | MS | MS |
| Chromatography type | Reversed phase | Reversed phase | HILIC | HILIC |
| Chromatography system | Thermo Dionex Ultimate 3000 | Thermo Dionex Ultimate 3000 | Thermo Dionex Ultimate 3000 | Thermo Dionex Ultimate 3000 |
| Column | ACE Excel 2 C18-PFP (100 x 2.1mm, 2um) | ACE Excel 2 C18-PFP (100 x 2.1mm, 2um) | Waters Acquity BEH C18 (50 x 2.1mm,1.7um) | Waters Acquity BEH C18 (50 x 2.1mm,1.7um) |
| MS Type | ESI | ESI | ESI | ESI |
| MS instrument type | Orbitrap | Orbitrap | Orbitrap | Orbitrap |
| MS instrument name | Thermo Q Exactive Orbitrap | Thermo Q Exactive Orbitrap | Thermo Q Exactive Orbitrap | Thermo Q Exactive Orbitrap |
| Ion Mode | POSITIVE | NEGATIVE | POSITIVE | NEGATIVE |
| Units | Peak Height | Peak Height | Peak Height | Peak Height |
Chromatography:
| Chromatography ID: | CH001554 |
| Chromatography Summary: | Metabolomics |
| Instrument Name: | Thermo Dionex Ultimate 3000 |
| Column Name: | ACE Excel 2 C18-PFP (100 x 2.1mm, 2um) |
| Chromatography Type: | Reversed phase |
| Chromatography ID: | CH001555 |
| Chromatography Summary: | Metabolomics |
| Instrument Name: | Thermo Dionex Ultimate 3000 |
| Column Name: | ACE Excel 2 C18-PFP (100 x 2.1mm, 2um) |
| Chromatography Type: | Reversed phase |
| Chromatography ID: | CH001556 |
| Chromatography Summary: | Lipidomics |
| Instrument Name: | Thermo Dionex Ultimate 3000 |
| Column Name: | Waters Acquity BEH C18 (50 x 2.1mm,1.7um) |
| Chromatography Type: | HILIC |
| Chromatography ID: | CH001557 |
| Chromatography Summary: | Lipidomics |
| Instrument Name: | Thermo Dionex Ultimate 3000 |
| Column Name: | Waters Acquity BEH C18 (50 x 2.1mm,1.7um) |
| Chromatography Type: | HILIC |
MS:
| MS ID: | MS001976 |
| Analysis ID: | AN002122 |
| Instrument Name: | Thermo Q Exactive Orbitrap |
| Instrument Type: | Orbitrap |
| MS Type: | ESI |
| MS Comments: | Metabolomics |
| Ion Mode: | POSITIVE |
| MS ID: | MS001977 |
| Analysis ID: | AN002123 |
| Instrument Name: | Thermo Q Exactive Orbitrap |
| Instrument Type: | Orbitrap |
| MS Type: | ESI |
| MS Comments: | Metabolomics |
| Ion Mode: | NEGATIVE |
| MS ID: | MS001978 |
| Analysis ID: | AN002124 |
| Instrument Name: | Thermo Q Exactive Orbitrap |
| Instrument Type: | Orbitrap |
| MS Type: | ESI |
| MS Comments: | Lipidomics |
| Ion Mode: | POSITIVE |
| MS ID: | MS001979 |
| Analysis ID: | AN002125 |
| Instrument Name: | Thermo Q Exactive Orbitrap |
| Instrument Type: | Orbitrap |
| MS Type: | ESI |
| MS Comments: | Lipidomics |
| Ion Mode: | NEGATIVE |
