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Subject: MOLECULAR SWITCH BOOSTS BRAIN ACTIVITY ASSOCIATED WITH
SCHIZOPHRENIA

U.S. Department of Health and Human Services NATIONAL INSTITUTES OF HEALTH
NIH News Eunice Kennedy Shriver National Institute of Child Health and Human
Development(NICHD) <http://www.nichd.nih.gov/> For Immediate Release:
Wednesday, August 13, 2008

CONTACT: Robert Bock or Marianne Glass Miller, 301-496-5133, <e-mail:
[log in to unmask]>

MOLECULAR SWITCH BOOSTS BRAIN ACTIVITY ASSOCIATED WITH SCHIZOPHRENIA Mouse
Study May Yield Insight, New System for Drug Testing

People with schizophrenia have an alteration in a pattern of brain
electrical activity associated with learning and memory.  Now, researchers
from the National Institutes of Health and Sweden's Karolinska Institute
have identified in mouse brain tissue a molecular switch that, when thrown,
increases the strength of this electrical pattern. The researchers found
that adding the brain chemical Neuregulin-1 to the brain tissue boosted the
electrical signals that the tissue generated.

"This finding may yield new insights into a form of altered brain activity
occurring in schizophrenia," said Duane Alexander, M.D., director of NIH's
Eunice Kennedy Shriver National Institute of Child Health and Human
Development (NICHD).  "It may also lead to new methods for screening drugs
with potential as schizophrenia treatments."
 
The findings appear online in the journal "Cerebral Cortex."  The research
was conducted by Andre Fisahn, Ph.D, of the Karolinska Institute, in
collaboration with Andres Buonanno, Ph.D, and his colleagues in NICHD's
section on Molecular Neurobiology.  Dr. Buonanno was the study's senior
author.

Schizophrenia affects about 1.1 percent of the U.S. population.  Symptoms
include delusions, hallucinations, disordered thinking and social
withdrawal. 

As nerve impulses travel through the brain, they emit weak electrical
signals that can be measured through sensors attached to the scalp.  The
different parts of the brain emit different kinds of electrical signals.
These signals vary with the kinds of mental activity taking place within the
brain.

Dr. Buonanno and his colleagues studied electrical patterns known as gamma
oscillations.  Ordinarily, gamma oscillations occur when people are involved
with learning and memory tasks, Dr. Buonanno said.  In people with
schizophrenia, however, the strength of the gamma oscillations is reduced.
 
"With schizophrenia, the gamma oscillations are fainter," Dr. Buonanno said.
"It's analogous to tuning in the weak signal of a distant station on your
car radio, as opposed to picking up the strong signal of a station that's
nearby."

Dr. Buonanno and his colleagues studied brain sections from the hippocampus,
a brain region involved in learning and memory.  The hippocampus also is a
major source of gamma oscillations.

The researchers first chemically stimulated the brain sections, in effect
jump starting them so that they began generating gamma oscillations.  After
the researchers exposed the sections to Neuregulin-1, the strength of the
gamma oscillations increased dramatically.  

Like a key fits into a lock, Neuregulin-1 fits into a special site, or
receptor, on the surface of brain cells.  Specifically, Neuregulin-1 binds
to the receptor known as ERB4.  

Further tests confirmed the role of Neuregulin-1 in boosting gamma
oscillations.  The researchers soaked the hippocampus sections in a drug
that blocks ERB4.  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 a
particular type of neuron (a specialized cell involved in the transmission
of information).  Known technically as parvalbumin expressing neurons, these
neurons slow the transmission of electrical signals through the brain.

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 which were genetically incapable of producing the ERB4
receptor also have fewer parvalbumin expressing neurons than do genetically
normal mice.

"Our study has uncovered an interesting lead," Dr. Buonanno said.  "Future
studies of brain regions rich in ERB4 receptors may yield important
information on the nature of schizophrenia." 

Dr. Buonanno added that studies of how various drugs affect the ERB4
receptor and parvalbumin expressing neurons may lead to novel drug
treatments for schizophrenia.

Other authors of the study were Jorg Neddens and Leqin Yan, also of the
NICHD Section on Molecular Neurobiology.

Information on schizophrenia is available from NIH's National Institute of
Mental Health at
<http://www.nimh.nih.gov/health/publications/schizophrenia/summary.shtml>.

The NICHD sponsors research on development, before and after birth;
maternal, child, and family health; reproductive biology and population
issues; and medical rehabilitation.  For more information, visit the
Institute's Web site at <http://www.nichd.nih.gov/>.

The National Institutes of Health (NIH) -- The Nation's Medical Research
Agency -- includes 27 Institutes and Centers and is a component of the U.S.
Department of Health and Human Services. It is the primary federal agency
for conducting and supporting basic, clinical and translational medical
research, and it investigates the causes, treatments, and cures for both
common and rare diseases. For more information about NIH and its programs,
visit <www.nih.gov>.
 
##

This NIH News Release is available online at:
<http://www.nih.gov/news/health/aug2008/nichd-13.htm>.

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