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

> **NIH NIH R21** · PURDUE UNIVERSITY · 2021 · $308,499

## Abstract

R21AG068787 is entitled, “PFOS-induced dopaminergic neurodegeneration across nematode, amphibian, and
rodent models”. The primary focus is on Parkinson’s disease (PD) endpoints as part of NIA’s Comparative
Biology of Neurodegeneration (to PAR-17-039) program. 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 data in nematode and amphibian models suggest that
exposure to PFAS, especially perfluorooctane sulfonate (PFOS) induces neurotoxicity. The main project
addresses an important gap on how PFAS exposure leads to long-term neurological disease risk through testing
the following hypothesis: that species-specific responses to PFOS-induced dopaminergic neurodegeneration will
advance understanding of the biology of PD. This hypothesis is being 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. The funded project has 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 neurotoxicity induced by PFOS exposure.
Throughout our examination of the PFAS literature, along with our own preliminary data newly collected from
R21AG068787, it has become apparent that Alzheimer’s disease (AD)-relevant expansion is strongly supported.
PFAS (specifically PFOS) exposure produces modulation of several critical AD proteins in multiple model
systems. Thus, in an effort to be highly responsive to NOT-AG-20-034 (entitled, “Alzheimer’s-focused
administrative supplements for NIH grants that are not focused on Alzheimer’s disease”), we will leverage
R21AG068787 to test the following hypothesis that is aimed at exploring overlap between AD and PD: PFOS
exposure will produce an AD-relevant phenotype and that species-specific responses will advance
understanding of the biology of AD. This supplement leverages the original scope, adding AD-relevant
endpoints, where amyloid beta aggregation, tau aggregation/hyperphosphorylation and other key AD
biochemical events will be assessed. Furthermore, AD-relevant neurobehavioral analyses are added in this
supplement. Given PFAS exposures are widespread (detectable in >99% of human blood), it is critical to
determine if such exposures represent a neurologica...

## Key facts

- **NIH application ID:** 10289079
- **Project number:** 3R21AG068787-01S1
- **Recipient organization:** PURDUE UNIVERSITY
- **Principal Investigator:** Jason R Cannon
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $308,499
- **Award type:** 3
- **Project period:** 2020-09-01 → 2022-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10289079

## Citation

> US National Institutes of Health, RePORTER application 10289079, PFOS-induced dopaminergic neurodegeneration across nematode, amphibian, and rodent models (3R21AG068787-01S1). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10289079. Licensed CC0.

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