Targeting expression of NRG1, which makes a protein important for brain development, may hold promise for treating at least some patients with the brain disorder.
Like patients with schizophrenia, adult mice biogenetically-engineered to have higher NRG1 levels showed reduced activity of the brain messenger chemicals glutamate and γ-aminobutyric acid (GABA). The mice also showed behaviors related to aspects of the human illness.
“They genetically engineered mice so they could turn up levels of NRG1 to mimic high levels found in some patients then return levels to normal,” explained senior author Dr Lin Mei from the Medical College of Georgia at Georgia Regents University.
“They found that when elevated, mice were hyperactive, couldn’t remember what they had just learned and couldn’t ignore distracting background or white noise. When they returned NRG1levels to normal in adult mice, the schizophrenia-like symptoms went away.”
While schizophrenia is generally considered a developmental disease that surfaces in early adulthood, the team found that even when they kept NRG1 levels normal until adulthood, mice still exhibited schizophrenia-like symptoms once higher levels were expressed. Without intervention, they developed symptoms at about the same age humans do.
“This shows that high levels of NRG1 are a cause of schizophrenia, at least in mice, because when you turn them down, the behavior deficit disappears,” Dr Mei said. “Our data certainly suggests that we can treat this cause by bringing down excessive levels of NRG1 or blocking its pathologic effects.”