How exactly does schizophrenia work at the cellular level? Researchers from three labs at the Perelman School of Medicine at the University of Pennsylvania are discovering how differences in the interactions between various types of nerve cells lead to schizophrenia. Specifically, they have found a link between genetic risk factors for the disease and how the brain responds to sound.
These discoveries were made possible through the use of electrophysiological, anatomical, and immunohistochemical techniques, as well as a unique high-speed imaging technique.
“Our work provides a model linking genetic risk factors for schizophrenia to a functional disruption in how the brain responds to sound, by identifying reduced activity in special nerve cells that are designed to make other cells in the brain work together at a very fast pace,” explains lead author Gregory Carlson, PhD, assistant professor of Neuroscience in Psychiatry.
“We know that in schizophrenia this ability is reduced, and now, knowing more about why this happens may help explain how loss of a protein called dysbindin leads to some symptoms of schizophrenia.”
Previous genetic studies revealed that some forms of the gene for dysbindin were found in people with schizophrenia. In fact, a finding at Penn showed that the dysbindin protein is reduced in most schizophrenia patients, suggesting it is involved in a common cause of the disorder.
For the current PNAS study, Carlson, Steven J. Siegel, MD, PhD, associate professor of Psychiatry, director of the Translational Neuroscience Program; and Steven E. Arnold, MD, director of the Penn Memory Center, studied a mouse with a mutated dysbindin gene to figure out how reduced dysbindin protein may cause symptoms of schizophrenia.
The researchers demonstrated several sound-processing problems in the brains of mice with the mutated gene. Specifically, a certain set of nerve cells that control fast brain activity lose their effectiveness when dysbindin protein levels are lowered.
These specific nerve cells inhibit brain activity at a record pace, essentially turning large numbers of cells on and off in a way that is necessary to process the huge amount of information traveling through the brain.
Prior Penn research in the lab of Michael Kahana, PhD has also revealed that the fast brain activity disrupted in mice with the dysbindin mutation is critical for short-term memory in humans. This brain activity is reduced in schizophrenics and resistant to current therapy. These findings may suggest new avenues of treatment for currently untreatable symptoms of schizophrenia, says Carlson.
The research is published in the Proceedings of the National Academy of Sciences and was funded in part by the National Institutes of Mental Health.