World Trade Center dust induces nasal and neurological tissue injury while propagating reduced olfaction capabilities and increased anxiety behaviors

Abstract

Objective: Previous in vitro and in vivo World Trade Center particulate matter (WTC_PM) exposure studies have provided evidence of exposure-driven oxidative/nitrative stress and inflammation on respiratory tract and aortic tissues. What remains to be fully understood are secondary organ impacts due to WTC_PM exposure. This study was designed to test if WTC particle-induced nasal and neurologic tissue injury may result in unforeseen functional and behavioral outcomes.

Material and Methods: WTC_PM was intranasally administered in mice, evaluating genotypic, histopathologic, and olfaction latency endpoints.

Results: WTC_PM exposure was found to incite neurologic injury and olfaction latency in intranasally (IN) exposed mice. Single high-dose and repeat low-dose nasal cavity insults from WTC_PM dust resulted in significant olfaction delays and enduring olfaction deficits. Anxiety-dependent behaviors also occurred in mice experiencing olfaction loss including significant body weight loss, increased incidence and time spent in hind stretch postures, as well as increased stationary time and decreased exploratory time. Additionally, WTC_PM exposure resulted in increased whole brain wet/dry ratios and wet whole brain to body mass ratios that were correlated with exposure and increased exposure dose (p<0.05).

Discussion: The potential molecular drivers of WTC_PM-driven tissue injury and olfaction latency may be linked to oxidative/nitrative stress and inflammatory cascades in both upper respiratory nasal and brain tissues.

Conclusion: Cumulatively, these data provide evidence of WTC_PM exposure in relation to tissue damage related to oxidative stress-driven inflammation identified in the nasal cavity, propagated to olfactory bulb tissues and, potentially, over extended periods, to other CNS tissues.

Keywords:

• World Trade Center dust
• particulate matter exposure
• central nervous system
• intranasal instillation

View correction statement:

Correction

Correction Statement

This article was originally published with errors, which have now been corrected in the online version. Please see Correction (http://dx.doi.org/10.1080/08958378.2022.2126145).

Acknowledgements

Authors would also like to acknowledge the following persons for their courageous task of collecting WTC dusts on Sep. 12 and 13 near the Ground Zero. The field team was led by Dr. Mitchell Cohen and consisted of: M. Blaustein, SI Hsu, J Duffey, J Clemente, K Schermerhorn, G Chee, C Prophete, and J Gorczynski. Acknowledgements are also extended to the Mary Sano Alzheimer’s Disease Research Center (ADRC) P30 grant at the Icahn School of Medicine at Mount Sinai and their contribution to critical review of this manuscript.

Disclosure statement

No potential conflict of interest was reported by the author(s).

Authors’ contributions

MH conceived, designed, coordinated, and performed all experiments, as well as statistical analyses and manuscript drafts. JV, TG, ML, SG and LCC assisted in study design and manuscript editing. All authors read and approved the final manuscript.

Authors’ information

MH received her Ph.D. from New York University and holds MS degrees in Exposure Assessment from New York University and Molecular Biology from Montclair State University. She has worked as a consultant to life science, medical device, and contract research companies for the last decade. MH currently serves as Associate Director of Occupational Toxicology in Merck Research Laboratories and is Chair of Merck’s Industrial Toxicology Advisory Committee which sets formal health-based exposure limit standards to support worker protection/safety and product quality.

Data availability statement

The datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request.

Additional information

Funding

This research was supported by NYU’s National Institute of Environmental Health Sciences Center of Excellence [ES000260], R21ES026731 and Training Grants [T32ES007324, F31ES 025591].