Controlling Schizophrenia Gene Eliminates Symptoms In Mice
May 23, 2013

Controlling Schizophrenia Gene Could Help Tame The Disease

Brett Smith for - Your Universe Online

Geneticists at the“¯Medical College of Georgia at Georgia Regents University have identified a key regulatory gene that appears to play a role in the classic symptoms of schizophrenia.

According to a report in the“¯journal“¯Neuron on the discovery targets expression of a gene known as Neuregulin-1 and could lead to promising treatments for patients with the psychological disorder.

In the study, the geneticists engineered mice to have elevated levels of Neuregulin-1 activity, replicating levels found in some patients diagnosed with schizophrenia. They observed the reduced activity of the brain messengers glutamate and GABA, a major inhibitory neurotransmitter. These mice were also seen to interact less with other animals and frequently failed certain thinking tasks, behaviors also seen in humans with schizophrenia.

"The deficits reversed when we normalized Neuregulin-1 expression in animals that had been symptomatic, suggesting that damage which occurred during development is recoverable in adulthood," explained Dr. Lin Mei, a professor at the university.

"While mouse models can't really do full justice to a complex brain disorder that impairs our most uniquely human characteristics, this study demonstrates the potential of dissecting the workings of intermediate components of disorders in animals to discover underlying mechanisms and new treatment targets," said Dr. Thomas R. Insel, a director at the National Institutes of Health, which funded the study.

"Hopeful news about how an illness process that originates early in development might be reversible in adulthood illustrates the promise of such translational research."

The geneticists were able to measure Neuregulin-1 activity fairly easily, as blood level indicators correlate well with those in the brain. To affect the mice, the researchers put a copy of the Neureglin-1 gene into mouse DNA. In front of that gene the team put a binding protein for doxycycline, an analogue for the antibiotic tetracycline, which stains the teeth of fetuses and babies. This causes the administration of tetracycline to result in a drop in Neureglin-1 activity.

"If you don't feed the mice tetracycline, the Neuregulin-1 levels are always high," said Mei, adding that normal levels of the gene are not affected by the antibiotic.

Mei said that high-levels of neuregulin-1 appear to activate kinase LIMK1, another potential target for intervention.

Previous research has shown that schizophrenia derives from damage to the developing fetal brain and is the result of a combination of genetic and environmental causes. While the genetic basis for the disease is still not well understood, some postmortem studies have found elevated levels of Neuregulin-1 gene activity in the prefrontal cortex for those diagnosed with the mental disorder.

Before the new study, scientists were not sure whether damage caused by elevated prenatal Neuregulin-1 expression could be reversed in adults.

The new study´s results indicate that schizophrenia deriving from disruptions early in brain development and adult patients whose schizophrenia stems from faulty Neuregulin 1 activity might benefit from a reduction in symptoms following treatments that isolate the overexpression of the gene or the protein that it codes for.