# Neurotoxic and neurodegenerative risks from chronic exposure to metal mixtures in e-cigarette aerosol

> **NIH NIH R01** · COLUMBIA UNIVERSITY HEALTH SCIENCES · 2024 · $81,124

## Abstract

SUMMARY
Recent research, done as part of the parent grant, resulted in the important revelation that e-cigarette (e-cig)
operating power may be more relevant for metal exposure and associated brain metal accumulation and
neurotoxicity than total aerosol dose (aerosol concentration times exposure duration). Our data show that metal
accumulation in e-cig aerosol from an open e-cig device massively and dose-dependently increases with
operating power within the range recommended by the manufacturer (30-50 W). Moreover, while our previous
2-month mouse exposure experiment, performed with e-cig aerosol produced at 40 W, revealed significant and
dose-dependent metal deposition and dyshomeostasis in mouse brain (Re et al., 2021), our latest data indicates
that the lower levels of metals measured in e-cig aerosol generated at 30 W do not cause overt metal deposition
in mouse brain even after 6 months of chronic exposure. Yet, this exposure paradigm caused some neurotoxicity,
especially in males carrying the Parkinson’s Disease (PD)-linked mutation, as shown by motor deficit and gait
impairment, potentially attributable to other aerosol components such as aldehydes. This recent finding leads to
the central hypothesis of this diversity supplement, that e-cig operating power may be more relevant for metal
exposure and associated brain metal accumulation and neurotoxicity than total aerosol dose. Leveraging the
experiments from the parent grant, we will rigorously evaluate the effects of operating power on the levels of
neurotoxic metals and aldehydes produced in e-cig aerosol, and the neurotoxic consequences of chronic
inhalation exposure to these aerosols. We will expand the aims of the parent grant by: 1) measuring metal and
aldehyde mixtures in e-cig aerosol produced at 30, 40 and 50 W, 2) examining cognitive/motor deficit progression
and endpoint brain neurotoxicity in mice exposed at 30 or 50 W and contrast these with our previous exposure
study performed at 40 W, and finally 3) untangling the modulatory effects of sex and genetic susceptibility to PD
on these neurotoxic outcomes. In Aim 1, we will determine metal and aldehyde mixture composition of e-cig
aerosols as a function of e-cig operating power by collecting e-cig aerosols from a device operated at three
different powers (30, 40 and 50 W). We will also evaluate coil aging effects on aerosol chemical composition, by
taking samples for several weeks over consecutive days (to cool down the device between uses). For Aim 2, we
will investigate whether operating power is a critical determinant of brain metal accumulation, neurobehavioral
toxicity and neuropathology in mice chronically exposed to e-cig aerosol. In Aim 3, we will evaluate whether sex
and genetic susceptibility to PD modify the dependence of the aerosol mixture neurotoxicity in mice on e-cig
operating power (30-50 W). Our findings could support regulatory interventions (e.g., limiting operating power)
ultimately resulting in reduced neur...

## Key facts

- **NIH application ID:** 11101461
- **Project number:** 3R01ES032954-04S1
- **Recipient organization:** COLUMBIA UNIVERSITY HEALTH SCIENCES
- **Principal Investigator:** Markus Hilpert
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $81,124
- **Award type:** 3
- **Project period:** 2021-09-08 → 2026-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/11101461

## Citation

> US National Institutes of Health, RePORTER application 11101461, Neurotoxic and neurodegenerative risks from chronic exposure to metal mixtures in e-cigarette aerosol (3R01ES032954-04S1). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/11101461. Licensed CC0.

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