Seminar Recap: Sex Dependent Neurotoxicity of Ambient Ultrafine Particulate Matter

Between its contributions to heart disease, stroke, lower respiratory infections in children, and chronic obstructive pulmonary disease, air pollution plays a big role in our health. In fact, the World Health Organization believes that air pollution contributes to over 7 million premature deaths annually.

Joshua Allen, Ph.D.

Joshua Allen, Ph.D.

“So they’re really making this firm statement now that air pollution is the largest single environmental health risk,” said Joshua Allen, Ph.D., research assistant professor of environmental medicine.

But the health risks don’t end there, as there are now close to a dozen studies linking autism and schizophrenia to early air pollution exposure. Hoping to expand on these findings, Allen is now studying how the ultrafine particles (UFPs) that accompany air pollution into the lungs can affect the growing brain.

His work has shown significant differences between how these UFPs affects neonatal male and female mice. He shared his results at the CTSI Seminar Series on Women’s Health on Oct. 28.

UFP study

To administer his study, Allen collected air using a device that draws in 5,000 liters of air per minute, and  concentrating it 10- to 20-fold. The resulting enriched air contained approximately 200,000 UFPs per cubic centimeter, or about the same amount present in the air around an active expressway.

He then exposed neonatal mice to the UFP-enriched air, and used a variety of tests to measure their neurological development.

In one learning test, the mice were rewarded with food after pressing a sequence of levers. Normally-developing mice would improve their test accuracy over time, but that didn’t happen for the male mice exposed to the UFP-enrich air. During the test, if they pressed an incorrect lever, a light would turn off, shutting the reward system down temporarily.

“What’s really interesting in males is that they don’t stop responding,” said Allen. “The whole box shuts down, and for a normal animal, you would expect the response to then stop, because they would never be reinforced when the lights areoff. But the males didn’t stop. They just kept whaling away on the levers.”

This effect adversely impacted their ability to learn, and also had implications for impulsivity. Allen said that it wasn’t his intention to study how the exposures affected males and females differently, but rather that the data pushed him in that direction.

Conclusions and future directions

Ultimately, both males and females did show some neurological damage after exposure, but males were significantly more sensitive to the UFP-enrich air.

“We think the protection in females is probably related to differences in microglia colonization, and it might be a testosterone-mediated mechanism,” said Allen.

Allen is now following up on several other studies that have shown certain types of air pollution, such as diesel exhaust particles, can affect males and females differently. He’s also looking at early-life air pollution exposure in humans and looking at whether home location correlates with the onset of the autism.

“This was all very surprising to us,” said Allen. “We didn’t start out as experts in this type of thing, and we’re learning as we go, but given the links between autism and air pollution, we want to know more about this topic.”

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