Lead Exposure Contributes to Schizophrenia Onset in Rats

When exposed to lead, rats’ brains demonstrated similar similarities to human schizophrenia patients, according to findings published in Translational Psychiatry. The researchers believe that these results add to the hypothesis that lead is a factor in schizophrenia onset.

Researchers from Columbia University Mailman School of Public Health discovered that lead negatively affects cells in 3 brain areas that are also implicated in schizophrenia patients: the medial prefrontal cortex, the hippocampus, and the striatum. In rat models, exposure to lead before birth and the early part of their lives affected these areas of the brains. In the mice models, the density of brain cells known as Parvalbumin Positive GABAergic interneurons (PVGI), declined by about a third, which is the same percentage decline seen in human schizophrenia patients, the researchers said.

“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,” senior author Tomás Guilarte, PhD, chair of Environmental Health Sciences at the Mailman School, explained in a press release.

The researchers also identified a dopamine receptor, called D2R, at which the rate of increase matched the documented human schizophrenia patients’ brains’ behavior.

In a related study, the researchers determined that rats exposed to lead showed a much stronger reaction to cocaine than healthy rat controls. The researchers injected the lead exposed rats with cocaine to gauge their reaction. The investigators compared the rates at which the lead exposed rats ran around their cages to their lead free control rats. The lead exposed, cocaine injected rats ran around the cages at twice the distance of the lead free control rats. The authors say this behavior is important because it is, again, similar to human schizophrenia patients — who are known to have a heightened response to cocaine.

“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,” continued first author Kirstie Stansfield, PhD, associate research scientist at the Mailman School.