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Your Environment. Your Health.

More Evidence that Lead Plays a Role in Schizophrenia

Tomás R. Guilarte, Ph.D.
Columbia University Health Sciences
NIEHS Grants R01ES006189, R01ES020465, P30ES009089

An NIEHS grantee and colleagues report strong similarities between the brains of people with schizophrenia and the brains of rats chronically exposed to lead from the prenatal period through adolescence, adding evidence that early lead exposure primes the brain for schizophrenia later in life.

The researchers found rats that had received chronic developmental lead exposure showed detriments in three brain areas known to be involved in schizophrenia: the medial prefrontal cortex, the hippocampus, and the striatum. Compared to control rats not exposed to lead, the exposed rats showed an approximately one-third decrease in density of Parvalbumin-Positive GABAergic interneurons (PVGI), which are critical to cognitive function. Using imaging technology, the researchers identified higher levels of D2 dopamine receptor, a hallmark of schizophrenia, in the striatum of lead exposed rats.

Psychosis, a characteristic symptom of schizophrenia, has been linked to subcortical dopaminergic hyperactivity. To determine whether lead exposed animals expressed this hyperactivity, the researchers administered cocaine to both control and lead-exposed rats and measured their locomotor response. The lead-exposed rats showed hyperactivity in the subcortical dopaminergic system.

Overall, the study in rats showed that developmental lead exposure reproduces the specific neuropathology and dopamine system changes seen in people with schizophrenia.

Citation: Stansfield KH, Ruby KN, Soares BD, McGlothan JL, Liu X, Guilarte TR. 2015. Early-life lead exposure recapitulates the selective loss of parvalbumin-positive GABAergic interneurons and subcortical dopamine system hyperactivity present in schizophrenia. Transl Psychiatry 5:e522.


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