# PFOS-induced dopaminergic neurodegeneration across nematode, amphibian, and rodent models

> **NIH NIH R21** · PURDUE UNIVERSITY · 2021 · $185,236

## Abstract

Parkinson's disease (PD) is a debilitating movement disorder (affecting ~5 million world‐wide) resulting from
selective death of dopamine (DA) neurons. To date, numerous rarely encountered exposures have been
investigated as risk factors, but none have been clearly linked to PD. Further, the translation of therapeutics that
are promising in animal studies to successful clinical trials has been very poor. These gaps in the field suggest
serious weaknesses in the utilization of animal models in PD research. Most PD studies test hypotheses in single
model systems. However, there are clear advantages with respect to increasing the strength of the findings and
advancing the field through understanding species differences. This R21 aims to be highly responsive to PAR‐
17‐039 (Comparative Biology of Neurodegeneration) by testing PD‐relevant neurodegeneration across three
phylogenetically diverse animal model systems. In the spirit of an R21, the proposal utilizes high risk/high
reward approaches, where novel risk factors will be tested to advance the understanding of the biology of PD.
Per‐ and polyfluoroalkyl substances (PFAS) are widespread environmental contaminants that have been
investigated as developmental toxicants, with little information on long‐term neurotoxicity. Our preliminary
mechanistic and neuropathology data in nematode and amphibian models suggest that exposure to PFAS,
especially perfluorooctane sulfonate (PFOS) induces selective PD‐relevant, DAergic neurotoxicity. This project
will address an important gap on how PFAS exposure leads to long‐term neurological disease risk. We will test
the hypothesis: that species‐specific responses to PFOS‐induced dopaminergic neurodegeneration will advance
understanding of the biology of PD. Importantly, the hypothesis will be tested across 3 animal model systems,
where concordance will strengthen findings, and discordance will identify biological aspects of species‐specific
sensitivity to environmentally‐induced neurodegeneration. We will test our hypothesis through two aims: Aim
1. To identify species specific‐PFOS doses that induce DAergic neurodegeneration. PFOS doses will be
harmonized across systems to achieve brain levels that bear environmental relevance. Harmonization of internal
dose levels to set external applied dosages for each model system will allow us to interrogate mechanistic
hypothesis under comparable insults; Aim 2. Identify neurobiological underpinnings across species that
contribute to differential sensitivity to PFOS‐induced dopaminergic neurodegeneration. Here, we will identify
species‐specific differences in neurodegeneration that may underlie critical aspects of selective dopaminergic
neurotoxicity induced by PFOS exposure. We will conduct comparative biology studies that are both phenotypic
and mechanistic. Resultant data will be critical in determining: 1) Which species is best suited to PFOS
neurodegeneration studies; 2) Identifying which pathogenic pathways directly c...

## Key facts

- **NIH application ID:** 10241311
- **Project number:** 5R21AG068787-02
- **Recipient organization:** PURDUE UNIVERSITY
- **Principal Investigator:** Jason R Cannon
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $185,236
- **Award type:** 5
- **Project period:** 2020-09-01 → 2023-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10241311

## Citation

> US National Institutes of Health, RePORTER application 10241311, PFOS-induced dopaminergic neurodegeneration across nematode, amphibian, and rodent models (5R21AG068787-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10241311. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*