Study reported in Cerebral Cortex found that Neuregulin-1 heightens the otherwise weak signal.
A group of researchers working with mice have found that the chemical Neuregulin-1 boosts the strength of the brain electrical pattern associated with learning and memory in the patients with schizophrenia.
The team studied electrical patterns known as gamma oscillations. “With schizophrenia, the gamma oscillations are fainter,” explains Andres Buonanno, Ph.D., of the NIH’s Eunice Kennedy Shriver National Institute of Child Health and Human Development. The group worked with brain sections from the hippocampus.
First the scientists chemically stimulated the brain sections, to jump start the generation of gamma oscillations. Next they exposed the sections to Neuregulin-1. At that point the electrical signals became much stronger.
Further tests confirmed the role of Neuregulin-1 in boosting gamma oscillations. The investigators soaked the hippocampus sections in a drug that blocks ERB4, the receptor to which Neuregulin-1 binds. When the researchers added Neuregulin-1, the hippocampus sections did not show an increase in gamma oscillations.
Similarly, the researchers then added Neuregulin-1 to hippocampus sections of mice that were genetically incapable of producing the ERB4 receptor. Once again the animals’ brains failed to show any increase in gamma oscillations.
The researchers chose to study Neuregulin-1 and ERB4 because earlier studies had shown that people with schizophrenia often have alterations in the genes that contain the information needed to make these substances.
“For the first time, we were able to show that Neuregulin-1, which has been genetically implicated in schizophrenia, affects a brain activity that appears to be altered in schizophrenia,” Dr. Buonanno said.
In addition, the researchers found that ERB4 receptors were abundant on parvalbumin-expressing neurons. Studies performed at autopsy have found that people with schizophrenia have fewer parvalbumin-expressing neurons than do people who do not have schizophrenia. In their study, Dr. Buonanno and his colleagues reported that the mice that were genetically incapable of producing the ERB4 receptor also have fewer parvalbumin-expressing neurons than genetically normal mice.
Besides NIH scientists, Andre Fisahn, Ph.D., of the Karolinska Institute also took part in this study. The findings appear online in the journal Cerebral Cortex.