Summary of Study ST002768
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 PR001725. The data can be accessed directly via it's Project DOI: 10.21228/M8QX5M 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 | ST002768 |
| Study Title | Dysregulation of neural activity and microglia function following exposure to the global environmental contaminant perfluorooctane sulfonate (PFOS) |
| Study Summary | Humans are chronically exposed to complex chemical mixtures and, correspondingly, researchers are disentangling the contribution of different contaminants to human neuropathologies. Per- and polyfluoroalkyl substances (PFAS) are biopersistent pollutants and, due to their diverse applications, have become global contaminants. Perfluorooctane sulfonate (PFOS), a prevalent PFAS congener, impairs humoral immunity; however, its impact on innate immunity is unclear. Given the critical roles of innate immune cells, namely microglia, in brain development and homeostasis, we asked whether exposure adversely affects microglial function. Herein, we demonstrate developmental PFOS exposure produces microglial activation and upregulation of the microglia activation gene p2ry12. PFOS-induced microglial activation heightened microglial responses to brain injury, in the absence of increased cell death or inflammation. Use of the photoconvertible calcium indicator CaMPARI revealed PFOS exposure heightened neural activity, while optogenetic silencing of neurons was sufficient to normalize microglial responses to injury. Through an untargeted metabolome wide association study (MWAS), we further determined that PFOS-exposed larvae exhibit significant neurochemical imbalances. Exposure to the perfluorooctanoic acid, an immunotoxic PFAS, did not alter neuronal activity or microglial behavior, further supporting a role for neural activity as a critical modifier of microglial function. Together, this study reveals how contaminant-induced changes in brain activity can shape brain health. |
| Institute | Brown University |
| Last Name | Paquette |
| First Name | Shannon |
| Address | 70 Ship Street |
| shannon_paquette@brown.edu | |
| Phone | 4018636125 |
| Submit Date | 2022-09-28 |
| Raw Data Available | Yes |
| Raw Data File Type(s) | cdf |
| Analysis Type Detail | LC-MS |
| Release Date | 2023-09-28 |
| Release Version | 1 |
Select appropriate tab below to view additional metadata details:
Combined analysis:
| Analysis ID | AN004504 | AN004505 |
|---|---|---|
| Analysis type | MS | MS |
| Chromatography type | Reversed phase | HILIC |
| Chromatography system | Thermo Vanquish | Thermo Vanquish |
| Column | Thermo Hypersil Gold Vanquish, 50 mm X 2.1 mm x 1.9 µm | Thermo Syncronis HILIC 50 mm X 2.1 mm x 3 µm |
| MS Type | ESI | ESI |
| MS instrument type | Orbitrap | Orbitrap |
| MS instrument name | Thermo Q Exactive HF-X Orbitrap | Thermo Q Exactive HF-X Orbitrap |
| Ion Mode | NEGATIVE | POSITIVE |
| Units | unitless | unitless |
Chromatography:
| Chromatography ID: | CH003384 |
| Chromatography Summary: | The reverse-phase LC was performed with a C18 column at a constant temperature of 60ºC. Mobile phase A contained 2 mM aqueous ammonium acetate and mobile phase B contained 2 mM ammonium acetate in acetonitrile. Metabolites were eluted from the column at a constant flow rate of 0.5 mL/minute using a mobile phase gradient as follows: equilibration with 2.5% B for 1 minute, increase to 100% B over 11 minutes and held for 2 minutes, and back to 2.5% B over 1 minute and held for 1.5 minutes (total run time 16.5 minutes, data were collected from 0.05 to 12.5 minutes). |
| Instrument Name: | Thermo Vanquish |
| Column Name: | Thermo Hypersil Gold Vanquish, 50 mm X 2.1 mm x 1.9 µm |
| Column Temperature: | 60ºC |
| Flow Gradient: | equilibration with 2.5% B for 1 minute, increase to 100% B over 11 minutes and held for 2 minutes, and back to 2.5% B over 1 minute and held for 1.5 minutes (total run time 16.5 minutes, data were collected from 0.05 to 12.5 minutes) |
| Flow Rate: | 0.5 mL/minute |
| Solvent A: | 2 mM aqueous ammonium acetate |
| Solvent B: | 2 mM ammonium acetate in acetonitrile |
| Chromatography Type: | Reversed phase |
| Chromatography ID: | CH003385 |
| Chromatography Summary: | The normal-phase LC was performed with a HILIC column at a constant temperature of 25ºC. Mobile phase A contained 2 mM ammonium acetate in acetonitrile and mobile phase B contained 2 mM aqueous ammonium acetate. Metabolites were eluted from the column at a constant flow rate of 0.2 mL/minute using a solvent gradient as follows: equilibrate with 10% B for 1 minute, increase to 65% B for 9 minutes and hold for 3 minutes, decrease to 10% over 1 minute and hold for 1 minute. |
| Instrument Name: | Thermo Vanquish |
| Column Name: | Thermo Syncronis HILIC 50 mm X 2.1 mm x 3 µm |
| Column Temperature: | 25ºC |
| Flow Gradient: | equilibrate with 10% B for 1 minute, increase to 65% B for 9 minutes and hold for 3 minutes, decrease to 10% over 1 minute and hold for 1 minute |
| Flow Rate: | 0.2 mL/minute |
| Solvent A: | 2 mM ammonium acetate in acetonitrile |
| Solvent B: | 2 mM aqueous ammonium acetate |
| Chromatography Type: | HILIC |
