Spatial transcriptomic profiling uncovers the molecular effects of the neurotoxicant polychlorinated biphenyls (PCBs) in the brains of adult mice

Budhaditya Basu; Nicole M. Breese; Sal Lombardi; Hui Wang; Xueshu Li; Destiny Tiburcio; Zachary Niemasz; Stacy E. Beyer; Laura E. Dean; Rachel F. Marek; Michal Toborek; Hans-Joachim Lehmler; Snehajyoti Chatterjee

doi:10.1101/2025.07.24.665575

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Spatial transcriptomic profiling uncovers the molecular effects of the neurotoxicant polychlorinated biphenyls (PCBs) in the brains of adult mice

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Spatial transcriptomic profiling uncovers the molecular effects of the neurotoxicant polychlorinated biphenyls (PCBs) in the brains of adult mice

Budhaditya Basu, Nicole M. Breese, Sal Lombardi, Hui Wang, Xueshu Li, Destiny Tiburcio, Zachary Niemasz, Stacy E. Beyer, Laura E. Dean, Rachel F. Marek, …

bioRxiv

Cold Spring Harbor Laboratory

07/26/2025

DOI: 10.1101/2025.07.24.665575

PMCID: PMC12330554

PMID: 40777386

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Preprint (Author's original)This preprint has not been evaluated by subject experts through peer review. Preprints may undergo extensive changes and/or become peer-reviewed journal articles. Open Access

Abstract

Environmental toxicants, such as polychlorinated biphenyls (PCBs), are highly stable synthetic organic compounds that are present in air, water, and soil. PCBs have been identified in post-mortem human brains of individuals with neurodegenerative diseases, indicating a possible link between environmental factors and disease risk. Research has revealed an association between PCB exposure and cognitive decline. Therefore, it is crucial to evaluate how PCB mixtures relevant to humans affect brain function and cognition. To investigate the effects of PCBs on memory and transcriptomic profiles, we exposed adult male C57BL/6J mice orally to a synthetic PCB mixture daily. After seven weeks of exposure, the mice were assessed in a spatial object recognition task (SOR) to evaluate long-term spatial memory. Our findings showed that mice exposed to PCBs exhibited deficits in long-term spatial memory. To examine the molecular effects of PCB on the brain, we used a spatial transcriptomics technique to analyze gene expression changes in five brain regions: the hippocampus, neocortex, thalamus, caudal putamen, and fiber tracts. Our analysis of spatial gene expression revealed the molecular signatures influenced by PCB in these susceptible brain regions of mice. Network analysis suggests that these changes are associated with higher chlorinated PCBs present in the brain. Additionally, we show that PCB exposure disrupts the expression of tight junction proteins, which are crucial for maintaining the integrity of the blood-brain barrier (BBB). Thus, our results offer mechanistic insights into how PCB exposure affects brain function and cognition.

Details

Title: Subtitle: Spatial transcriptomic profiling uncovers the molecular effects of the neurotoxicant polychlorinated biphenyls (PCBs) in the brains of adult mice
Creators: Budhaditya Basu - University of Iowa
Nicole M. Breese - University of Iowa
Sal Lombardi - University of Iowa, Neuroscience and Pharmacology
Hui Wang - University of Iowa
Xueshu Li - University of Iowa
Destiny Tiburcio - University of Miami Health System
Zachary Niemasz - University of Iowa
Stacy E. Beyer - University of Iowa
Laura E. Dean - University of Iowa
Rachel F. Marek - University of Iowa
Michal Toborek - University of Miami Health System
Hans-Joachim Lehmler - University of Iowa
Snehajyoti Chatterjee - University of Iowa
Resource Type: Preprint
Publication Details: bioRxiv
DOI: 10.1101/2025.07.24.665575
PMID: 40777386
PMCID: PMC12330554
NLM abbreviation: bioRxiv
ISSN: 2692-8205
eISSN: 2692-8205
Publisher: Cold Spring Harbor Laboratory
Language: English
Date posted: 07/26/2025
Academic Unit: Public Health Administration; Occupational and Environmental Health; Iowa Neuroscience Institute; IIHR--Hydroscience and Engineering; Neuroscience and Pharmacology
Record Identifier: 9984945084202771

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