In recent weeks, wildfires — and the potential health effects of resulting poor air quality — have drawn attention from millions of Americans. Smoke from Canadian wildfires made its way to the United States and at times seemed to blanket many parts of the country. In June, as smoke-filled skies made national headlines, I participated in the Human Health and the Environment Research Symposium at the University of Rochester Medical Center (URMC), located in New York. Among other topics, I shared how NIEHS is helping to lead the National Institutes of Health Climate Change and Health Initiative, which will advance critical research into how climate-related weather events, including wildfires, may affect human health.
During the symposium, long-time NIEHS grant recipient Deborah Cory-Slechta, Ph.D., delivered a thought-provoking presentation on potential connections between air pollution, attention-deficit hyperactivity disorder (ADHD), and other neurodevelopmental challenges. Dr. Cory-Slechta is an internationally renowned scientist who has worked for more than four decades to shed light on how environmental agents can affect brain development and influence neurodevelopmental disorders. A professor at URMC, she holds appointments in the departments of environmental medicine, neuroscience, and public health sciences.
After the conference, I caught up with Dr. Cory-Slechta to learn more about her research and the state of the science on how air pollution affects the brain and its development. I also asked what inspired her to become a researcher, and she described her early interest in science.
Links to Alzheimer’s, Parkinson’s, and more
Rick Woychik: What do we know about links between air pollution and neurological disorders?
Deborah Cory-Slechta: For many years, most air pollution research examined cardiopulmonary effects, and it seemed that the fact that the head was attached to the rest of the body was sort of ignored [laughs]. It has only been in the last 10 or 15 years that scientists have started to pay attention to how air pollution influences the brain.
There is now a significant amount of epidemiological literature that shows associations between air pollution and many neurodevelopmental disorders and neurodegenerative diseases. Scientists have found links between air pollution and autism spectrum disorder, ADHD, Alzheimer’s disease, Parkinson’s disease, schizophrenia, and even multiple sclerosis. Still, there are many unanswered questions, and research into how air pollution affects the brain is in its infancy.
One thing we know is that when it comes to air pollution, particle size matters. I have focused on what scientists call ultrafine particles, or UFPs, which are 100 nanometers or less in size and invisible to the human eye. Because UFPs have a greater surface area-to-mass ratio than larger particles, they also carry more contaminants on their carbon base. When individuals breathe these particles, they go into the bloodstream, but they can also go up the nose and directly into the brain, bypassing the blood-brain barrier.
Ultrafine particles can result from wildfires, burn pits, and any scenario where particulate matter is being generated. Our understanding so far is that wildfires tend to generate a greater number of these smaller particles. Importantly, the composition of contaminants will depend on where that wildfire is and what is included. When homes, cars, and other such things start burning, you can just imagine the pollutants that are getting into the smoke.
Studying real-world exposures
RW: Among its other efforts, your group uses rodent models to investigate the potential effects of ultrafine particles. Can you expand on that work for Environmental Factor readers?
DC-S: We have one of the very few facilities left in the country where we can study real-world exposure to ultrafine particles and assess how such exposures may affect development. My colleagues can actually pull in air from outside the building, separate its components by particle size, and then use our rodent models to examine exposures involving ultrafine particles. Being able to study such ambient air is important if we are to mimic actual exposures in humans.
With that ability to study ultrafine particles, we started conducting studies involving developmental exposures, looking for biological and behavioral changes that are shared across a variety of neurodevelopmental and neurodegenerative disorders. One thing that became clear in mice was a vulnerability of the male brain to these early exposures. They tended to show more pathological changes and behavioral changes than females. The male vulnerability has largely involved the equivalent of third trimester human exposures.
Also, in our mice, we have done gestational exposures during the equivalent of first and second human trimesters, and there we see that both sexes are affected, but they are affected in different ways. Scientists have known for years that there clearly are sex differences in the brain, but we do not yet know what specifically accounts for these differences in vulnerability to exposures during different developmental periods.
One question our team wants to address is what components of air pollution from wildfires and other sources may be harming the brain during development. If we know what the contaminants are, then we could potentially monitor them, regulate them, and protect public health.
Right now, we know that ultrafine particles can carry all kinds of metals and trace elements into the brain. For example, iron is elevated in the brain in every neurodegenerative disease I have looked at, and now we are seeing it in some neurodevelopmental disorders.
Our team can build exposure chambers to generate metal aerosols such as iron, copper, and so forth, and we have started to assess developmental exposures as well as adult exposures in our rodent models. We are excited about a forthcoming paper that examines high levels of iron exposure in adults, where we are looking for characteristics of Alzheimer’s disease and assessing sex differences.
Removing metals from the brain
RW: Is there any evidence that excess iron or other metals can eventually leave the brain?
DC-S: Interestingly, one of the things that we found with our collaborator are these things in the brain called corpora amylacea, which appear to be there to take up neuronal cellular debris and remove it from the brain. We discovered that they contain both exogenous and endogenous iron after iron exposures. These waste containers can get pretty large, and not a lot is known about how they form, how they leave the brain, and so forth.
They have been found in the cervical lymph nodes, which would suggest that they can get out of the brain. But what happens if the brain is making too many or they get too large? Do they break back down and create a re-exposure? We do not yet have answers to these questions.
Going forward, we want to look at the brain’s lateral ventricle. Corpora amylacea should be moving back into the cerebrospinal fluid to leave the brain through that portal specifically. And we will study other brain regions because obviously these particles move. When I see metal imbalances, they seem to be worse in the cortex, so perhaps there is vulnerability in that region.
(Rick Woychik, Ph.D., directs NIEHS and the National Toxicology Program.)