Columbia: A study of the brains of rats exposed to lead has uncovered striking
similarities with what is known about the brains of human schizophrenia
patients, adding compelling evidence that lead is a factor in the onset
of schizophrenia. Results of the study by scientists at Columbia University’s Mailman School of Public Health appear in the journal Translational Psychiatry.
The researchers found that lead had a detrimental effect on cells in
three brain areas implicated in schizophrenia: the medial prefrontal
cortex, the hippocampus, and the striatum of rats exposed to lead before
birth and in the early part of their lives. Density of brain cells
known as Parvalbumin-Positive GABAergic interneurons, or PVGI, declined
by approximately a third—at roughly the same percentage decline seen in
schizophrenia patients. They also identified higher levels of a dopamine
receptor called D2R. Again, the magnitude of the increase matched what
has been documented in human schizophrenia patients, and in a previous study of genetically engineered mice.
“The similarities in the brain structure and neuronal systems between
what we see in lead-exposed rats and human schizophrenia patients are
striking, and adds to a growing body of literature suggesting that early
lead exposure primes the brain for schizophrenia later in life,” says
senior author Tomás Guilarte, PhD, chair of Environmental Health Sciences at the Mailman School.
Brains of rats exposed to lead (right) had a lower cell density of parvalbumin-positive neurons compared with controls (left).
Cocaine Insights
In a related finding, the researchers found that rats exposed to lead
had a much stronger reaction to cocaine than healthy rat controls. In
the experiment, lead-exposed rats that were injected with cocaine ran
around in their cages at twice the distance of lead-free control rats.
The rat behavior is meaningful because it mirrors what is seen in
schizophrenia patients, who are known to have a heightened response to
the drug.
Schizophrenia is not the only possible consequence of lead exposure. A
follow-up experiment will allow the rats to self-administer cocaine in
order to test whether lead exposure plays a role in addiction.
“We are currently assessing the impact of lead exposure on both the
rewarding and reinforcing properties of addictive drugs like cocaine
while exploring the biological underpinnings of how lead exposure plays a
role in addiction,” says first author Kirstie Stansfield, PhD,
associate research scientist at the Mailman School.
Additional authors of the current study include Kristen N. Ruby,
Barbara Soares, Jennifer L. McGlothan, and Xinhua Liu—all of Columbia’s
Mailman School of Public Health. The research was supported by grants
from the National Institute of Environmental Health Sciences (ES006189,
ES020465, and P30ES009089).