Implications of air pollution on brain development and neurological health in children and older women

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A pair of recently published USC studies add to our growing understanding of how fine particle pollution — the tiny, inhalable pollutants from cars and power plants — impacts our brains.

The first study, published in Environment International, found that these fine particles — known as PM2.5 — may alter the size of a child’s developing brain, which may ultimately increase the risk for cognitive and emotional problems later in adolescence.

“At this young age, the neurons in children’s brains are expanding and pruning at an incredible rate. As your brain develops, it wants to create efficient pathways,” said lead author Megan Herting, an assistant professor at the Keck School of Medicine of USC.

“If these pathways are altered by PM2.5 exposure, and different parts of the brain are maturing and making connections at different rates, that might set you up for individual differences later on.”

USC, located in what the American Lung Association frequently cites as the most polluted city in the nation, is home to a robust air pollution research program.

Findings from its studies have led to changes in state and federal guidelines to improve air quality standards. One of its cornerstones is the USC Children’s Health Study, one of the largest and most detailed studies of the long-term effects of air pollution.

Herting’s team used MRI scans from nearly 11,000 children aged 9 and 10 from 21 cities across the United States and matched each scan with yearly pollution data for each child’s residence.

This is the first study of its kind to show that, even at relatively low levels, current PM2.5 exposure may be an important environmental factor that influences patterns of brain development in American children.

When they compared highly exposed kids with those who had less exposure to PM2.5, they saw differences. For example, areas associated with emotion were larger in highly exposed kids, while other areas associated with cognitive functioning were smaller.

Herting plans to follow the progress of the children, who are part of the ABCD Study, the largest long-term study of brain health and child development in the United States.

Eating fish could help protect women’s brains against fine particle pollution
The second study, published in Neurology, found that omega-3 fatty acids from consuming fish may protect against PM 2.5-associated brain shrinkage in older women.

Previous USC research showed that women in their 70s and 80s who were exposed to higher levels of air pollution experienced greater declines in memory and more Alzheimer’s-like brain atrophy than their counterparts who breathed cleaner air.

For this study, researchers looked at the brain MRIs of 1,315 women aged 65 to 80 and blood test results to determine levels of healthy omega-3 fatty acids in their blood.

“We found that women with higher blood levels of omega-3s had larger volumes of white matter in their brains.

Women living in locations with higher PM2.5 tended to have smaller white matter in their brains, but such damage that may be caused by PM2.5 was greatly reduced in women with high blood levels of omega-3 fatty acids,” said corresponding author Jiu-Chiuan Chen, an associate professor at the Keck School of Medicine of USC.

The brain’s white matter, in contrast to gray matter, makes up most of the volume of the brain.

It is the vast, intertwining system of neural connections that unites different regions of the brain that perform various mental operations.

White matter loss may be an early marker of Alzheimer’s disease.

About the Environment International study: In addition to Herting, other authors of the study include Dora Cserbik, Jiu-Chiuan Chen, Rob McConnell, Elizabeth R. Sowell, Daniel A. Hackman, all of USC; Kiros Berhane of Mailman School of Public Health of Columbia University; Eric Kan of Children’s Hospital Los Angeles; Joel Schwartz of Harvard T.H. Chan School of Public Health; and Chun C. Fan of UC San Diego.

Funding: The study was supported with grants from the National Institute of Environmental Health Sciences (P30ES007048-23S1, 3P30ES000002-55S1, P01ES022845), the Environmental Protection Agency (RD 83587201, RD 83544101) and the Rose Hills Foundation. The larger ABCD study is also supported by the National Institutes of Health (U01DA041048, U01DA050989, U01DA051016, U01DA041022, U01DA051018, U01DA051037, U01DA050987, U01DA041174, U01DA041106, U01DA041117, U01DA041028, U01DA041134, U01DA050988, U01DA051039, U01DA041156, U01DA041025, U01DA041120, U01DA051038, U01DA041148, U01DA041093, U01DA041089, U24DA041123 and U24DA041147).

About the Neurology study: In addition to Chen, other authors of the study include Xinhui Wang and Helena Chui of Keck; Cheng Chen and Ka He of Columbia University; Pengcheng Xun of Indiana University; Joel Kaufman of the University of Washington; Kathleen Hayden and Mark Espeland of Wake Forest School of Medicine; Eric Whitsel, Marc Serre and William Vizuete of University of North Carolina Chapel Hill; Tonya Orchard of Ohio State University; and William Harris of the University of South Dakota.

Funding: The study was supported with grants from the National Institutes of Health (R01AG033078, RF1AG054068 and RF1AG056111) and the National Institute of Environmental Health Sciences (R01ES025888).


Air pollution is a cocktail of suspended gases, solids, and liquid particles. While this mix contains numerous hazardous ingredients, such as ozone, sulfur dioxide, and carbon monoxide, the component that appears most concerning for the brain is PM.

The US Environmental Protection Agency (EPA) regulates PM10 and PM2.5, defined as particles less than 10 and 2.5 micrometers in diameter, respectively.

PM2.5, also known as fine particulate matter, generally comes from smoke, dust, and vehicle exhaust.

Because PM2.5 is so tiny – 30 times smaller than the width of the average human hair – it can remain airborne for long periods of time, infiltrate buildings, and penetrate the body.

Ultrafine particles, which measure less than 0.1 micrometer across, may be even worse offenders.

Yet the miniscule mass of these particles makes them difficult to monitor. They remain unregulated by the EPA.

Fine and ultrafine particulate matter tends to circumvent the mechanisms that the human body has evolved to deflect, detain, and destroy unwelcome visitors.

“The health effects of air pollution are all about particle size,” says Cory-Slechta. Studies suggest that these tiny particles can even go up the nose and be carried straight to the brain via the olfactory nerve (5) – hence bypassing the blood–brain barrier.

And they don’t travel alone. On their surfaces these particles carry contaminants, from dioxins and other chemical compounds to metals such as iron and lead.

“PM is simply acting as a vector,” says Masashi Kitazawa, a molecular neuropathologist at the University of California, Irvine.

“It might be a number of chemicals that get into the brain and act in different ways to cause damage.”

Because of their large surface area relative to their volume, the smallest particles are the biggest offenders. Cory-Slechta’s research has largely focused on lead and mercury, neurotoxic metals that are abundant in air pollution. “Ultrafine particles are like little Trojan horses,” she says. “Pretty much every metal known to humans is on these.”

Metal-toting particles that reach the brain can directly damage neurons. Both the particles themselves and their toxic hitchhikers can also cause widespread harm by dysregulating the activation of microglia, the immune cells in the brain.

Microglia may mistake the intruders for pathogens, releasing chemicals to try to kill them. Those chemicals can accumulate and trigger inflammation. And chronic inflammation in the brain has been implicated in neurodegeneration (6).

Particles may also afflict the brain via the bloodstream. Research shows that small particles can slip through the plasma membrane of alveoli – the tiny air sacs in the lungs – and get picked up by capillaries.

The particles are then distributed around the body in the blood. Although some of these particles may eventually breach the blood–brain barrier, a pollutant need not enter the brain to cause trouble there. The immune system can react to particles in the lung or bloodstream, too, triggering widespread inflammation that affects the brain.

Even an ingested particle could have indirect neurological effects, via the gut. Researchers now recognize strong connections between the gut microbiome and the brain (7), and studies show that delivering fine particles to the gut can cause systemic inflammation (8).

Figure2
After 14 days of exposure to pollutants during the gestational period, researchers found deposits of trace elements silica (Si), iron (Fe), and aluminum (Al) in rat brains (Top Right). They also found a loss of myelin—the insulating sheath around nerve fibers—in the corpus callosum of male rat brains (Bottom Right). Image credit: Uschi M. Graham (University of Kentucky, Lexington, KY) (Top) and Deborah Cory-Slechta (Bottom).

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Source:
USC

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