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Doctoral defence of Liudmila Saveleva, MSc, 22 Sept 2023: Investigating the effects of air pollution on the brain

The doctoral dissertation in the field of Neurobiology will be examined at the Faculty of Health Sciences at Kuopio campus.

What is the topic of your doctoral research? Why is it important to study the topic?

The aim of my doctoral research was to explore the effects of ultrafine particles (UFPs), a prevalent component of air pollution, on brain health and find the main cellular and molecular mechanisms altered by UFP exposure. Additionally, since recent epidemiological studies found that life in highly polluted areas contributes to the incidence of Alzheimer's Disease (AD), we placed a special emphasis on understanding the relationship between UFP exposure and AD.

Studying the impact of UFPs and air pollution in general on brain health is of paramount importance for several reasons. According to the World Health Organization (WHO), 99% of humanity breathes polluted air. UFPs are the smallest fraction of particulate matter comprising air pollution that has been recently recognized as extremely hazardous to human health. Due to their size of ≤ 0.1 µm, UFPs have the high potential to reach deep areas of our lungs, travel in our bloodstream, and translocate to the brain. Meanwhile, contrary to bigger particles found in polluted air, WHO still have not included UFPs in air quality guidelines, and there is no legislation to limit UFP concentrations. Recently, WHO stated that further research on UFPs-triggered health effects and approaches for monitoring those particles in the ambient air are urgently warranted. By understanding the adverse effects of UFPs on brain health, especially in the context of neurodegenerative diseases like AD, we can gain a clearer picture of the public health challenges posed by air pollution. This knowledge is vital not only for the scientific community but also for policymakers, as it can guide interventions and shape policies to mitigate the detrimental effects of air pollution on societal health.

What are the key findings or observations of your doctoral research?

The research found that even short-term exposure to UFPs at relatively low doses can lead to elevated cytokine levels, alter the expression of brain membrane drug transporter proteins, and affect gene expression in the olfactory bulb, the brain area responsible for odour discrimination. By using a mouse model of AD, we found that UFPs can induce oxidative stress in the AD hippocampi without altering toxic amyloid-beta load. The study offers the first-ever evidence of the effects of air pollution exposure on the brain drug transporter system. It also provides a detailed description of the transcriptomic responses of the olfactory bulb to UFP exposure, advancing the understanding of the effects of environmental insults on the olfactory system. The identification of novel transcripts and pathways affected by UFP exposure opens new avenues for research into the molecular mechanisms underlying pollution-induced toxicity and proposes new exposure biomarkers.

How can the results of your doctoral research be utilised in practice?

My research findings emphasise the urgent need for revisions to air quality policies worldwide, particularly concerning UFP levels in ambient air. It provides valuable insights for policymakers, healthcare professionals, and other researchers. By understanding the effects of UFPs on the brain, policymakers can make informed decisions about air quality standards. Healthcare professionals can use this knowledge to advise patients, especially those in high-risk groups or those living in heavily polluted areas. The identification of potential biomarkers and affected pathways can guide future research and interventions aimed at mitigating the effects of air pollution on brain health.

What are the key research methods and materials used in your doctoral research?

The research utilized inhalation exposure to UFPs in the whole-body chambers to study effects of air pollution on the brains of both wild-type and mouse model of AD. Key methods included: subacute exposure to UFPs (mice received 2 weeks of inhalation exposure to freshly generated UFPs to study their effects on the brain), analysis of brain membrane transporter proteins, and transcriptomic analysis using Next-Generation Sequencing technology.

This is a multidisciplinary research project that required combined efforts from Finnish, German and Czech scientists from environmental toxicology, emission chemistry, neuroscience, molecular biology, and pharmacology fields trying together to decipher how small particles from polluted air can affect brain homeostasis.

The doctoral dissertation of Liudmila Saveleva, MSc, entitled Investigating effects of exposure to ultrafine particulate matter in the brain will be examined at the Faculty of Health Sciences. The Opponent in the public examination will be Associate Professor Paola Palestini of the University of Milano-Bicocca, Italy, and the Custos will be Professor Katja Kanninen of the University of Eastern Finland.

Doctoral defence