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.

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Study IDST002768
Study TitleDysregulation of neural activity and microglia function following exposure to the global environmental contaminant perfluorooctane sulfonate (PFOS)
Study SummaryHumans 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 NamePaquette
First NameShannon
Address70 Ship Street
Emailshannon_paquette@brown.edu
Phone4018636125
Submit Date2022-09-28
Raw Data AvailableYes
Raw Data File Type(s)cdf
Analysis Type DetailLC-MS
Release Date2023-09-28
Release Version1
Shannon Paquette Shannon Paquette
https://dx.doi.org/10.21228/M8QX5M
ftp://www.metabolomicsworkbench.org/Studies/ application/zip

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Subject:

Subject ID:SU002875
Subject Type:Fish
Subject Species:Danio rerio
Taxonomy ID:7955
Age Or Age Range:24-120 hours post-fertilization
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