論文 - 詳細
| RRC ID | 79080 |
|---|---|
| 著者 | Paquette SE, Martin NR, Rodd A, Manz KE, Allen E, Camarillo M, Weller HI, Pennell K, Plavicki JS. |
| タイトル | Evaluation of Neural Regulation and Microglial Responses to Brain Injury in Larval Zebrafish Exposed to Perfluorooctane Sulfonate. |
| ジャーナル | Environ Health Perspect |
| Abstract |
BACKGROUND:Per- and polyfluoroalkyl substances (PFAS) are biopersistent, global pollutants. Although some in vitro and epidemiological studies have explored the neurotoxic potential of perfluorooctane sulfonate (PFOS), a prevalent PFAS congener, it is unknown how developmental PFOS exposure affects neuronal signaling, microglia development, and microglial-neuron communication. OBJECTIVES:We sought to determine the extent to which PFOS exposure disrupts brain health, neuronal activity, and microglia-neuron communication during development. In addition, although PFOS impairs humoral immunity, its impact on innate immune cells, including resident microglia, is unclear. As such, we investigated whether microglia are cellular targets of PFOS, and, if so, whether disrupted microglial development or function could contribute to or is influenced by PFOS-induced neural dysfunction. METHODS:Zebrafish were chronically exposed to either a control solution [0.1% dimethyl sulfoxide (DMSO)], RESULTS:Developmental PFOS exposure resulted in a shift away from the homeostatic microglia state, as determined by functional and morphological differences in exposed larvae, as well as up-regulation of the microglia activation gene p2ry12. PFOS-induced effects on microglia state exacerbated microglia responses to brain injury in the absence of increased cell death or inflammation. PFOS exposure also heightened neural activity, and optogenetic silencing of neurons or microglia independently was sufficient to normalize microglial responses to injury. An untargeted MWAS of larval brains revealed PFOS-exposed larvae had neurochemical signatures of excitatory-inhibitory imbalance. Behaviorally, PFOS-exposed larvae also exhibited anxiety-like thigmotaxis. To test whether the neuronal and microglial phenotypes were specific to PFOS, we exposed embryos to PFOA, a known immunotoxic PFAS. PFOA did not alter thigmotaxis, neuronal activity, or microglial responses, further supporting a role for neuronal activity as a critical modifier of microglial function following PFOS exposure. DISCUSSION:Together, this study provides, to our knowledge, the first detailed account of the effects of PFOS exposure on neural cell types in the developing brain in vivo and adds neuronal hyperactivity as an important end point to assess when studying the impact of toxicant exposures on microglia function. https://doi.org/10.1289/EHP12861. |
| 巻・号 | 131(11) |
| ページ | 117008 |
| 公開日 | 2023-11-1 |
| DOI | 10.1289/EHP12861 |
| PMID | 37966802 |
| PMC | PMC10650473 |
| MeSH | Animals Brain Injuries* Calcium Fluorocarbons* / toxicity Microglia Zebrafish |
| リソース情報 | |
| ゼブラフィッシュ | Tg(Huc:Kaede)rw0130a |