Stabilizing a gene reverses schizophrenia in mice
Scientists at Georgia Regents University may have discovered the key to reversing schizophrenia, a complex disorder that affects about 1% of the U.S. population.
In a mouse model, researchers found that by setting a gene that is typically overexpressed in schizophrenia back to normal, they were able to eliminate classic symptoms of the disorder in the animals.
The mice were genetically engineered so researchers could adjust the levels of neuregulin-1 to simulate high levels of the gene found in some patients. When the gene was elevated, the animals showed signs of hyperactivity, learning and memory problems, and distractions--all commonly associated with schizophrenia. When neuregulin-1 was reset to normal, the symptoms went away, the scientists reported in the journal Neuron.
Researchers found that even when they regulated neuregulin-1 at a normal level until mice reached the equivalent of adulthood--when the disorder typically surfaces in people--the animals still developed symptoms associated with schizophrenia once higher levels of the gene became expressed.
"This shows that high levels of neuregulin-1 are a cause of schizophrenia, at least in mice, because when you turn them down, the behavior deficit disappears," said Dr. Lin Mei, director of the Institute of Molecular Medicine and Genetics at the Medical College of Georgia at Georgia Regents University. "Our data certainly suggests that we can treat this cause by bringing down excessive levels of neuregulin-1 or blocking its pathologic effects."
High neuregulin-1 levels have been found in only a minority of patients, but small molecules to block the gene's signaling pathways could likely reduce neuregulin-1 levels in those individuals to provide relief to schizophrenia-related symptoms, said Mei.
Schizophrenia has multiple causes, many of which are unknown, making the disease difficult to diagnose and treat. Antipsychotic medications, which focus on reducing the activity of two neurotransmitters, are the most common therapy currently available.
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