Summary of project PR001725
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
| Project ID: | PR001725 |
| Project DOI: | doi: 10.21228/M8QX5M |
| Project Title: | Targeted Analysis of PFOS in Larval Zebrafish using LC-HRMS & Untargeted Metabolome Wide Association Study (MWAS) |
| Project 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 |
| Department: | Pathology and Laboratory Medicine |
| Last Name: | Paquette |
| First Name: | Shannon |
| Address: | 70 Ship Street |
| Email: | shannon_paquette@brown.edu |
| Phone: | 4018636125 |
| Funding Source: | NSF Major Research Instrumentation (MRI) award |
Summary of all studies in project PR001725
| Study ID | Study Title | Species | Institute | Analysis(* : Contains Untargted data) | Release Date | Version | Samples | Download(* : Contains raw data) |
|---|---|---|---|---|---|---|---|---|
| ST002768 | Dysregulation of neural activity and microglia function following exposure to the global environmental contaminant perfluorooctane sulfonate (PFOS) | Danio rerio | Brown University | MS* | 2023-09-28 | 1 | 36 | Uploaded data (23.1G)* |
