Schizophrenia-related Gene Deletion Alters Brain's Circuit System, Development

Researchers at the University of North Carolina-Chapel Hill (UNC) have discovered how the 22q11 gene deletion is associated with changes in brain development that affect how the circuit system in the brain is put together, as well as how the deletion of 22q11 impacts another subset of neurons in the brain's cerebral cortex.

Researchers in the UNC School of Medicine tracked basal and apical progenitors, two subclasses of neural stem cells, during early brain development in a mouse model with the 22q11 gene deletion. The basal progenitors divided more slowly than they should have, according to the researchers, which resulted in the development of a cortex that was not "generated in the proper numbers."

According to senior study author Anthony LaMantia, PhD, professor of cell and molecular physiology and co-director of the Silvio O. Conte Center for the Neuroscience of Mental Disorders, and the rest of the research team, they looked at another group of cells, GABAergic cells, thought to "put the brakes on electrical activity in mature cortical circuits." In the mouse model with the deleted 22q11 gene, the researchers found that the GABAergic neurons never correctly landed in the cortical layers of the brain.

Deletion of the 22q11 gene is a mutation that is known to confer the greatest genetic likelihood of schizophrenia. According to LaMantia and his fellow researchers, the study is the first to lend "clear support to the 'neurodevelopmental hypothesis,' which is the 'Hail Mary' of schizophrenia pathologists."

The next step in the research process is determining "how these alterations in the circuitry of the brain affect the behavior of the mouse."

"Now that we know what cells can be affected in schizophrenia, it opens up new avenues in thinking about the molecular mechanisms underlying this and other psychiatric illnesses," said LaMantia. "We can even begin to look for biomarkers of the disease that can be used for better diagnosis and treatment."

Results of the study will be presented by Daniel Meechan, PhD, a post-doctoral fellow in LaMantia's laboratory, at the Society for Neuroscience meeting in Chicago on October 17.