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Brain Cells Activity: New Treatment Target for Psychiatric Diseases

Medical College of Georgia researchers led by Dr. Lin Mei report in the May 24 issue of Neuron that, two genes important for human development keep a healthy balance between excitation and inhibition of brain cells. Incidentally, these genes are also implicated in cancer and schizophrenia.

The research showed that Neuregulin-1 and its receptor, ErbB4, promote inhibition at the site of inhibitory synapses in the brain by increasing release of GABA, a major inhibitory neurotransmitter.

In 2000, a research team led by Dr. Mei showed that neuregulin-1 and ErbB4 also are at excitatory synapses, communication points between neurons where the neurotransmitter glutamate excites cells to action. Here, neuregulin-1 and ErbB4 suppress excitation.

"Right beside the place where the excitatory synapse can be activated, there is also something that can suppress it," says Dr. Mei, chief of developmental neurobiology at MCG. "Now we have identified another novel target of neuregulin-1 which is the inhibitory synapse."

Together the findings reveal a check and balance for brain cell activity managed by neuregulin-1 in the brain's prefrontal cortex, where complex reasoning and decisions about appropriate social behavior occur, he says.

They also provide new treatment targets for psychiatric diseases such as schizophrenia and neurological disorders such as epilepsy, researchers say.

The genes are both associated with schizophrenia, a disease that affects about 1 percent of the population, but the exact role of malfunctioning neuregulin-1 signaling was unclear.

"(Dr. Mei's) findings help explain how a gene that is potentially causative in disorders like schizophrenia and bipolar disorder relate to a neurotransmitter that is critical for explaining the cognitive deficits associated with the illness," says Dr. Daniel R. Weinberger, director of the Genes, Cognition and Psychosis Program at the
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