Researchers at MIT's Picower Institute for Learning and Memory have found that inhibiting a key brain enzyme in mice reversed schizophrenia-like symptoms.
The finding, reported in the March 20 issue of Cell, identified how a particular gene controls this brain enzyme. Better understanding of the relationship could lead to new drug treatments for schizophrenia, the severe brain disorder that affects about 1 percent of the population and is characterized by hallucinations, delusions, poor social and emotional functioning and disorganized thoughts.
The Picower research focused on a gene known as DISC1 (short for "disrupted in schizophrenia 1"), which was first identified in the 1990s by researchers studying the genetic makeup of a large Scottish family with mental and behavioral disorders. DISC1 has since been shown to help brain neuronal cells migrate to their correct positions and to help new neurons grow in the developing brain, but its role was not well understood.
Now, Li-Huei Tsai, the Picower Professor of Neuroscience in MIT's Department of Brain and Cognitive Sciences, and colleagues have shown for the first time that DISC1 directly inhibits the activity of a brain enzyme called glycogen synthase kinase 3 beta, also known as GSK3B.
Lithium chloride, the mood-stabilizing drug often prescribed for schizophrenia and bipolar disorder, also acts on GSK3B.
"This work for the first time provides a detailed explanation of how DISC1 functions normally in our brains," said Tsai, a Howard Hughes Medical Institute investigator and director of the neurobiology program of the Stanley Center for Psychiatric Research at the Broad Institute of Harvard and MIT.
"With this new knowledge of the DISC1-GSK3B interaction, one of the goals is to develop new drugs targeting schizophrenia, providing some hope that this devastating disease will be treated more effectively in the near future," she said.
Growing new neurons