Toxins and the brain

By Gretchen Kroeger

A quick search for news stories on the topics of ADHD or learning and behavioral impairments will produce a considerably long list of results, and most written within the last few days. These headlines deal with the use of ADHD prescription drugs, a recent rise in number of women taking ADHD drugs, studies linking chemical X to ADHD in kids, links between chemical Y and autism, etc. But what’s going on? Why are so many children (and adults) being diagnosed with cognitive and behavioral disabilities?

A slew of research, from a variety of academic fields, is working on understanding the things in our lives that could impact the developing brain and lead to various developmental impairments. In March, Duke’s Superfund Research Center and Integrated Toxicology and Environmental Health Program co-hosted a day-long symposium to highlight this body of research, generate discussion, and encourage creativity and collaboration. The symposium, entitled “Cognitive Impairment Caused by Developmental Neurotoxic Exposure: Mechanisms, Consequences, and Therapeutic Treatment,” tackled the topic from a variety of perspectives and approaches.


Why the environment?

“The environment is a powerful determinant of health and disease, especially for children.” –  Dr. Philip Landrigan, from Mount Sinai’s Children’s Environmental Health Center.

If we are concerned about the impaired cognition observed in children and adults, then we should be concerned about the developing brain, since this is when our brain is being hardwired and programmed for the rest of our lives. And, if we’re concerned about the developing brain, then we should be concerned about the chemical environment in which it is developing.

This brings us to the research featured in the symposium. Research that seeks to answer the questions of which chemicals in our environment are impacting the developing brain? And, how are they actually able to impact development? And finally, when those first two questions are answered, what are possible treatments to prevent, reverse, or lessen those impacts to the developing brain?


The chemicals in our environment

Typically, when scientists talk about chemicals and environmental exposures, they’re talking about pharmaceuticals & cosmetics, pesticides, and/or industrial chemicals. There’s increasing concern about pharmaceuticals in drinking water; pesticide exposure for farmworkers, the general public, and honey bees; and communities adjacent to industrial facilities being exposed to contaminated soil, air, and water. But those studying environmental health are also looking at human exposure to things like metals (such as lead), environmental tobacco smoke, and nicotine.

We’ve known about the toxic nature of lead for about 30 years, which resulted in it being removed from gasoline, paint, and other products. Yet, children are still being exposed to lead at levels that are able to negatively affect brain development. Dr. Kim Dietrich, an MD at Cincinnati Children’s Hospital, is involved in a 35 year long prospective study in Cincinnati (1979-2014). Scientists are tracking the health of those enrolled in the study from conception or the first trimester through their 30’s by taking blood samples from kids every 3 months through age 5, biannually between ages 5 and 6, and then annually after that. With the results of the testing, they’re looking at links between lead exposure and behavioral outcomes such as criminality.

In her presentation, Dr. Frederica Perera addressed the fact that these environmental exposures to these chemicals don’t take place in isolation, but that people are also experiencing social stress, have their own genetic factors, and a unique diet. These factors are likely to influence the ways in which our bodies handle the environmental exposures to chemicals such as PAHs, environmental tobacco smoke (or secondhand smoke), and metals. To illustrate this, Perera discussed one of her studies in NYC in which she is collecting information about environmental exposures and psychosocial health for 720 mother-child pairs. The goal is to understand how pollution interacts with stressors such as material hardship (an example of a metric of psychosocial health).


Chemicals in our brain

We know we’re exposed to a variety of chemicals, but how exactly are they impacting the brain? This is the question tackled in the second half of the symposium.

Neurotransmitter signals control the fate of a cell; they tell the cell at various points in development what that cell should do: replicate, differentiate, grow, die, and/or learn. The issue with chemicals in the environment is that they are able to interfere with those normal signals and, thus, change the fate of cells.

Examples of this are seen in a few of Dr. Ed Levin’s findings shared during the symposium: 1) rats exposed to nicotine in utero and their ability to carry out learning tests when compared to rats not exposed to nicotine (they do much worse), 2) the brains of female rats are able to “bounce back” from exposure to chlorpyrifos much better than their male counterparts, and 3) the lessening or disappearance of normal sex-differences in learning and performance after exposure to neurotoxins. (For more of Levin’s recent findings, visit this summary of one of his recent publications.) Levin’s hypothesis for the mechanism of action? Males and females make differential use of parts of the brain: the frontal cortex vs. the hippocampus.

Dr. Ted Slotkin brought up the effects of cigarette smoking on the developing brain as another prime example. What are the effects of women smoking while pregnant? Consider a study that found kids of mothers who didn’t smoke performed better (higher IQ) than those whose mother’s did smoke. That may seem obvious, but what the study also found was that adolescents who smoked (and whose mothers smoked while pregnant) performed better than adolescents who didn’t smoke (and whose mothers smoked while pregnant). This is because smoking relieved the impact; thus, when adolescents tried to quit, there was a profound loss of synaptic activity.

The final speaker for the symposium, Dr. Charles Vorhees, spoke on the cognitive and behavioral effects of developmental exposure to manganese and stress in rats. There are a few reasons to be concerned about exposure to manganese during development: there is greater absorption in an underdeveloped gastrointestinal tract, it’s easier for manganese to cross the blood-brain barrier and enter the central nervous system, it accumulates in the basal ganglia, and it induces oxidative stress. The issue is that manganese and iron share the same transporter across membranes, meaning they compete with each other. Thus, impacts on child development (such as motor deficits) are more likely to be observed in areas where there are high levels of manganese exposure and high rates of iron deficiency.


So what now?

A recent Atlantic article highlighted research by Dr. Philip Landrigan and others looking at toxins and brain development. It’s definitely a topic that is increasingly in the public eye. So what now? The symposium was about presenting research and strengthening the network of those studying the impacts of neurotoxins. In addition to ideas being shared on Duke’s campus in March, conversations and brainstorming will continue as scientists continue to elucidate the impacts of toxins on brain development.