# Toxicant-induced neurotoxicity mediated by glia-neuron and gene-environment interactions in Parkinson's disease

> **NIH NIH R35** · FLORIDA INTERNATIONAL UNIVERSITY · 2023 · $16,193

## Abstract

The long term goal of our laboratory is to study the pathogenic mechanisms induced by
environmental toxicants, genetic mutations and gene-environment interactions in Parkinson’s
disease (PD) with the ultimate goal of developing disease-modifying therapeutics for this brain
disorder. Overall, our research projects address the following fundamental questions: 1) Gene-
environment interactions: Do mutations linked to PD render dopamine neurons more
susceptible to environmental toxicants? 2) Glia-neuron interactions: How do glial cells contribute
to the vulnerability of dopamine neurons in PD? 3) Excessive mitochondrial fission has been
demonstrated in genetic and toxicant-induced models of PD. Can mitochondrial fission and
fusion be targeted for PD treatment? These research topics are currently funded by the parent
grant (R35ES030523). This supplement is requested to support a summer student.
In the parent grant, we hypothesized that blocking Drp1 would attenuate autophagy impairment
induced by manganese (Mn). Since then, we have generated both in vitro and in vivo data to
support this hypothesis. However, so far, the focus has been on neurons. Given that Mn also
affects astrocytes and microglia, it is critical to also assess the effects of Mn and Drp1 in these
glial cells. For this summer project, the student will use primary astrocytes and microglia from
Drp1-KO mice and WT to study the effects of Mn on autophagy in these cell types and whether
Drp1-KO would be protective. This study is highly relevant and complementary to the parent
project. Successful completion of this study will provide preliminary data to advance the parent
project to using in vivo models to further investigate these in vitro data.

## Key facts

- **NIH application ID:** 10772772
- **Project number:** 3R35ES030523-05S1
- **Recipient organization:** FLORIDA INTERNATIONAL UNIVERSITY
- **Principal Investigator:** KIM TIEU
- **Activity code:** R35 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2023
- **Award amount:** $16,193
- **Award type:** 3
- **Project period:** 2019-06-01 → 2027-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10772772

## Citation

> US National Institutes of Health, RePORTER application 10772772, Toxicant-induced neurotoxicity mediated by glia-neuron and gene-environment interactions in Parkinson's disease (3R35ES030523-05S1). Retrieved via AI Analytics 2026-06-12 from https://api.ai-analytics.org/grant/nih/10772772. Licensed CC0.

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