Ultrafine particles (UFPs), which are the tiniest components of air pollution, have been found to interfere with the function of mitochondria in cells of the human olfactory mucosa, according to a recent study. The research revealed that UFPs originating from traffic sources disrupt the functioning of mitochondria in primary human olfactory mucosa cells by affecting processes such as oxidative phosphorylation and redox balance.
This study, led by the University of Eastern Finland, highlights the impact of traffic-related UFPs on mitochondrial functions in primary human olfactory mucosa cells, showing how these particles can hinder oxidative phosphorylation and disrupt redox balance. Notably, the responses of olfactory mucosa cells from individuals with Alzheimer’s disease differed from those of cognitively healthy individuals. The findings from this research have been published in the journal Redox Biology.
Air pollution is a significant global health concern and has been identified as a risk factor for neurodegenerative diseases, including Alzheimer’s disease (AD). Despite increasing evidence, the exact role of UFPs in the cellular and molecular changes in the human brain that lead to Alzheimer’s disease remains unclear.
The olfactory mucosa is a sensory tissue responsible for detecting odors and is directly exposed to the environment and in contact with the brain. Interestingly, one of the early clinical symptoms of Alzheimer’s disease is a diminished sense of smell. Researchers at the Kanninen Lab at the University of Eastern Finland use a physiologically relevant human-based in-vitro model of the olfactory mucosa, which is created from cells obtained from volunteer donors in collaboration with Kuopio University Hospital. Previous studies by the Kanninen Lab have demonstrated that this model mimics AD-related changes, making it well-suited for investigating the impact of air pollution on AD.
“Mitochondrial dysfunction is a crucial factor in the development and progression of neurodegenerative diseases like AD, and mitochondria are particularly vulnerable to environmental toxins. However, the relationship between UFPs and mitochondrial functions concerning AD has not been explored in the human olfactory mucosa before,” said Doctoral Researcher Laura Mussalo, the first author of the study from the Kanninen Lab at the University of Eastern Finland.
The study delved into the molecular mechanisms by which UFPs influence mitochondrial function in olfactory mucosa cells from individuals with normal cognitive function and those with Alzheimer’s disease. The researchers compared how mitochondria in these two groups responded by analyzing gene expression and conducting functional assessments. They also investigated whether different types of diesel fuels, such as fossil and renewable sources, had varying effects, and how modern engine aftertreatment devices, like particulate filters, impacted mitochondrial responses.
The research provided evidence that traffic-related UFPs can penetrate the inner mitochondrial membrane, disrupt oxidative phosphorylation, and lead to mitochondrial dysfunction. Changes in gene expression and functional studies confirmed disruptions in mitochondrial respiration, reduced levels of ATP, and disturbances in redox balance, resulting in increased oxidative stress. These effects were most pronounced when exposed to emissions from an untreated engine. However, emissions from an engine with aftertreatment devices had only minor effects. The responses observed in cells from individuals with AD differed slightly from those of the control group, indicating AD-related changes in olfactory mucosa cells following UFP exposure.
It is crucial to understand how air pollutants affect human health to guide policy decisions aimed at reducing air pollution effectively, ultimately alleviating the economic burden of associated health issues. This study sheds light on the heightened sensitivity of individuals with AD to the impacts of air pollution exposure and offers insights to support efforts to mitigate and prevent health issues stemming from UFP exposure.
This study is part of the TUBE project, which received funding from the European Union’s Horizon 2020 program. Additionally, the research was supported by grants from various organizations, including the Kuopio Area Respiratory Foundation, the Finnish Brain Foundation, Yrjö Jahnsson Foundation, Päivikki and Sakari Sohlberg Foundation, and The Finnish Cultural Foundation’s North Savo Regional Fund.
